GRADUATE STUDIES IN
BIOLOGICAL SCIENCES
2014 FACULTY RESEARCH GUIDE
Ecology and Evolutionary Biology | Molecular Biology and Biotechnology | Cellular, Developmental, and Neurobiology
WAYNE STATE UNIVERSITY:
A NATIONAL LEADER IN RESEARCH
The Carnegie Foundation for the Advancement of Teaching classifies
Wayne State University as RU/VH (Research University, Very High research
activity), a distinction held by only 3.5 percent of the nation’s universities.
Wayne State ranks among the nation’s top public universities for research
expenditures ($245.8 million total), according to the National Science
Foundation. Key growth areas include research in the life sciences, physical
sciences and engineering.
Wayne State partners with universities, industry and government to pioneer
advanced networking and technologies as a member of the national Internet2
research and development consortium, and is a founding member of the
Michigan LambdaRail, one of the most advanced very high-speed research
networks in higher education.
WSU’s 43-acre research and technology park, TechTown, includes the
headquarters of Asterand, a privately held company offering genomics and
proteomics researchers high-quality biological information and materials
needed to conduct research on common diseases such as cancer, heart disease
and brain disorders.
Highlights
n Students from 49 states and 60 countries
n More than 370 degree and certificate programs in 13 schools and colleges
n One of the nation’s 50 largest public research universities, with Michigan’s
most diverse student body
n More than 1,000 students in the School of Medicine, the largest singlecampus medical school in the country
n Affiliations with more than 100 institutions worldwide
n A partner in the University Research Corridor (URC) with the University of
Michigan and Michigan State University. The URC is an alliance designed
to leverage the intellectual capital of the state’s three public research
universities to transform, strengthen and diversify the state’s economy
n Home to the only National Institutes of Health branch dedicated to the
study of premature birth and infant mortality. Since locating to Detroit in
2002, the Perinatology Research Branch (PRB) has produced life-saving
research; cared for more than 20,000 at-risk mothers; contributed more
than $350 million to Michigan’s economy; and employed more than 130
physicians, researchers and staff members
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A DAY IN A WSU GRADUATE
STUDENT’S LIFE
What do Wayne State graduate students do in their free
time? Well, it depends on the kind of person you are.
If you are a foodie, you won’t have to go far. There are
wonderful restaurants around campus that offer authentic
Detroit bar food, French crepes, Mediterranean pita wraps,
different Asian cuisines (Indian, Chinese, Korean, Thai) and
completely vegetarian/vegan menus. If you are a sports
lover, downtown Detroit is where all the action is. All you
have to do is find great tickets — often available through
Wayne State at discounted rates for students. Theatre and
music enthusiasts also frequent downtown, where you will
find the magnificent Fox, Fisher and Hilberry theatres, as
well as the Detroit Opera House and Detroit Symphony
Orchestra. The Detroit Institute of Arts is a short walk from
campus, offering eclectic Friday night concerts, foreign
and domestic movies, and its world-class art collection. If
you are more health conscious, the Mort Harris Recreation
and Fitness Center is open all week and offers a variety
of cardio exercises, free-weight equipment, a three-lane
walking track and group fitness classes. You can also have
a relaxing swim or enjoy a game of tennis or racquetball
with your friends in the Matthaei Physical Education
Center on the west side of campus. If you’re a person who
likes to try out different things, then Thursdays in the D
might be of interest to you. It’s a Wayne State program
that organizes free or low-cost social activities for students
every Thursday evening like salsa dancing, pottery classes
and more. If you feel like exploring Detroit, shopping malls
or parks in the metro area, Zipcar is a useful resource.
Once a member of this car-sharing service, you can book
a car for about $7.50/hr and zip away. As the year moves
along, Detroit hosts a number of spectacular annual
festivals, including the Detroit Jazz Festival, Dally in the
Alley and Noel Night. All in all, Detroit offers an exciting
balance of graduate training and entertainment.
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RESEARCH BY DIVISIONS
The research and scholarship efforts
of the Department of Biological
Sciences at Wayne State University
encompass broad ranges of biology,
which are administratively organized
into three divisions:
n E cology and Evolutionary Biology
(EEB)
n M
icrobiology, Molecular Biology
and Biotechnology (MMBB)
n C
ellular, Developmental and
Neurobiology (CDNB)
Research in EEB addresses all levels
of biological organization from
the cellular to the landscape scale,
with expertise in responses to
environmental stress, ecotoxicology,
population and community dynamics,
population genetics and conservation,
invasive species, evolutionary
and functional genomics, and
developmental evolution. Faculty
in MMBB explore problems in viral
replication and virulence; social and
morphological dynamics in bacteria;
regulation of gene expression
in eukaryotes at the chromatin,
chromosomal and transcriptional
levels; and metabolic dynamics driven
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at the biochemical level of membrane
structures. Our CDNB division is
invested in projects in aging, cell
migration, cancer, intracellular
protein transport, exocytosis, neural
development and neurological
responses to stresses.
The numerous interactions between
these divisions are centered in the
overarching topics of development,
regulation of gene structure and
function, cell signaling stress
response, and ecological stability and
disturbance. Model systems such
as yeast, Drosophila, Aedes, Oryza,
Arabidopsis, E. coli, Tribolium and
Caenorabditis are all utilized in various
laboratories in the department.
Research is not restricted to classic
model organisms as studies are also
done in species ranging from crickets,
milkweed bugs and cave beetles
to suckers, mussels, aspen, spinach
and Myxococcus. Therefore, students
coming into our graduate programs
may choose from a wide array of
biological disciplines, benefitting from
the exposure to research and the
expertise of our diverse faculty.
FROM THE CHAIR
Thank you for your interest in the
graduate program of the Department
of Biological Sciences at Wayne State
University. As a department, we offer
a broad choice of courses, research
programs and teaching opportunities.
Each student follows an individualized
program, but the focus is on original
research that leads to participation in
national meetings and publications.
This prepares our students to go on
to positions at prominent universities
and research institutions. Our
graduates have achieved successful
careers in higher education,
government service and business.
Wayne State University is a comprehensive, nationally ranked research
institution and offers state-of-the-art research facilities. These include the
Advanced Genomics Technology Center, microscopy and proteomics core
facilities at the School of Medicine, and the Lumigen Instrument Center in the
Department of Chemistry. The Department of Biological Sciences is also well
equipped for molecular genetics, cell imaging, ecology and neurobiology.
Our Ph.D. students typically receive financial support for at least the first
five years of their program. The department has 49 graduate teaching
assistantships, supplemented by graduate research assistantships and
university fellowships. These generally provide tuition and health benefits as
well as a stipend. Safe, comfortable housing is available on campus and in
many nearby apartments.
Wayne State provides a unique setting to spend your time in graduate school.
Detroit is a major city with excellent cultural, sports and entertainment
attractions — many of them within walking distance of campus. Midtown
Detroit is experiencing a renaissance, with new buildings, restaurants,
museums and housing developing regularly. While offering the excitement and
diversity of urban life, metropolitan Detroit is in close proximity to Michigan’s
lakes, forests and recreational sites.
The Department of Biological Sciences has strong research programs across
the whole range of biological sciences. Our excellent research programs
are described in the pages that follow. If you have further questions, please
contact me at dnjus@wayne.edu, our graduate secretary at rpriest@wayne.
edu, or our graduate committee chair at apopadic@biology.biosci.wayne.
edu. I hope you will look closely at all we have to offer. We look forward to
receiving your application for graduate study.
­— David L. Njus
Professor and Chair
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SENSORY MECHANISMS INFLUENCE
PHYSIOLOGY AND LONGEVITY
JOY ALCEDO
Assistant Professor
Office: 2109 BSB
Phone: 313-577-3473
Email: joy.alcedo@wayne.edu
Website: www.alcedo-lab.wayne.edu
Ph.D., Molecular Biology and
Developmental Genetics, University
of Zurich, 1997
Postdoctoral Studies, Genetics and
Neurobiology of Aging, University of
California, San Francisco, 2004
Joined WSU faculty, 2012
For optimal survival, an animal has
to process complex environmental
information to generate the appropriate
physiological responses. An interesting
demonstration of this sensory influence
on physiology is the observation that
subsets of gustatory and olfactory
neurons can either shorten or lengthen
the lifespan of the nematode C. elegans,
responses that are also present in the
fruit fly Drosophila. Accordingly, the
nature of these neurons suggests that
some of the cues that affect lifespan
are food-derived and that perception
of these cues alone can exert different
effects on lifespan. Consistent with
this idea, we have recently found
that the sensory system influences
lifespan through food-type recognition,
which is distinct from food-level
restriction (commonly known as calorie
restriction). In addition, we have shown
that the sensory influence on lifespan
via food-type recognition involves
the activities of specific neuropeptide
signaling pathways under particular
environmental conditions.
physiology and lifespan include the many
insulin-like peptides (ILPs) of C. elegans
and Drosophila. We have found that a C.
elegans ILP combinatorial code regulates
distinct developmental switches that can
lead to physiological states that affect
lifespan. Thus, we aim to determine the
molecular and cellular bases through
which these different neuropeptides
process sensory information and
promote physiological changes that
correlate with lifespan changes.
Considering that age and environment
are significant risk factors in disease
development, our studies should yield
insight into the mechanisms of many
age-related diseases.
Sensory neurons affect lifespan,
presumably by promoting physiological
changes that alter organismal
homeostasis, which is modulated by
neuropeptide signaling. Aside from the
neuropeptide neuromedin U pathway
that processes food-type information
which, in turn, alters C. elegans lifespan,
other neuropeptides that affect
S E L E C T E D P U B L I C AT I O N S
Alcedo J., Flatt T., Pasyukova E.G.
2013. Neuronal inputs and outputs
of aging and longevity. Front Genet
4:71.
Chen Z., Hendricks M., Cornils
A., Maier W., Alcedo J., Zhang Y.
2013. Two insulin-like peptides
antagonistically regulate aversive
olfactory learning in C. elegans.
Neuron 77:572-585.
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Cornils A., Gloeck M., Chen Z.,
Zhang Y., Alcedo J. 2011. Specific
insulin-like peptides encode
sensory information to regulate
distinct developmental processes.
Development 138:1183-1193.
Maier W., Adilov B., Regenass M.,
Alcedo J. 2010. A neuromedin U
receptor acts with the sensory system
to modulate food type-dependent
effects on C. elegans lifespan. PLoS
Biol 8:e1000376
Alcedo J., Kenyon C. 2004. Regulation
of C. elegans longevity by specific
gustatory and olfactory neurons.
Neuron 41:45-55.
THE MOLECULAR MECHANISMS OF
EXOCYTOSIS AND ENDOCYTOSIS
In many parts of the human body, cells
communicate with one another through
messages encoded in neurotransmitter
and hormone-signaling molecules. The
process controlling the release of these
molecules is called exocytosis. During
exocytosis, secretory vesicles fuse with
the plasma membrane, releasing their
contents into the extracellular space.
Neurotransmitters and hormones then
diffuse to receptors on target cells,
triggering ionic or metabolic changes.
To maintain a constant cell surface
area, vesicle membranes and their
constituents are subsequently retrieved
via compensatory endocytosis. The
goal of our research program is to
understand the structure, function and
regulation of the molecular “machines”
mediating exocytosis and endocytosis.
Two areas on which we currently focus
are listed below.
Dynamin as a nexus between
exocytosis and endocytosis: Exocytosis
and endocytosis have long been thought
of as discrete and opposite, segregated
on the cell membrane and orchestrated
by distinct groups of proteins. However,
we recently showed that at least one
essential endocytic protein – Dynamin
– also influences vesicle fusion and
content release during exocytosis
(Anantharam, et. al, 2011). Dynamin
is a large, modular protein with several
important functional domains. During
endocytosis, dynamin forms rings around
the necks of budding vesicles, triggering
cooperative GTP hydrolysis and fission.
Its role in exocytosis is more opaque.
We are actively engaged in investigating
the mechanistic basis for dynamin
function during exocytosis. The project
involves the use of transgenic animals,
electrophysiology and optical imaging.
Synaptotagmin and membrane
curvature: The focus of these studies
is on the regulation of membrane
topological changes by the Ca2+ sensor
synaptotagmin. Synaptotagmin’s
function in exocytosis is inextricably
tied to its ability to bend and deform
membranes. To date, the most
compelling mechanistic models for
synaptotagmin function have been
derived from reconstituted fusion
reactions and negative-stain EM. The
limitation of these approaches is that
they do monitor real-time membrane
topological changes and do not report
on exocytosis in living cells. Our goal is to
understand how synaptotagmin shapes
the membrane during exocytosis. To this
end, we use polarized light microscopy
in reconstituted systems as well as living
mammalian cells.
ARUN ANANTHARAM
Assistant Professor
Office: 2117 BSB
Phone: 313-577-5943
Email: anantharam@wayne.edu
Website: anantharamlab.wayne.edu
Ph.D., Physiology and Biophysics,
Cornell University, 2007
Postdoctoral Fellow, University of
Michigan, 2007-11
Joined WSU faculty, 2011
S E L E C T E D P U B L I C AT I O N S
Passmore D.R., Rao T.C., Peleman
A.R., Anantharam A. 2014. Imaging
Plasma Membrane Deformations
With pTIRFM. J Vis Exp. (in press)
Passmore D.R., Rao T.C., Anantharam
A. 2014. Real-Time Investigation
of Plasma Membrane Deformation
and Fusion Pore Expansion Using
Polarized TIRFM. Methods in
Molecular Biology (in press)
Lama R.D., Charlson K., Anantharam
A., Hashemi P. 2012. Ultrafast
Detection and Quantification of Brain
Signaling Molecules with Carbon
Fiber Microelectrodes. Analytical
Chemistry 84:8096-8101.
Anantharam A., Onoa B., Edwards
R.H., Holz R.W., Axelrod D. 2010.
Localized topological changes of the
plasma membrane upon exocytosis
visualized by polarized TIRFM. J Cell
Biol 188:415-428.
Anantharam A., Bittner M.A., Aikman
R.L., Stuenkel E.L., Schmid S.L.,
Axelrod D., Holz R.W. 2011. A new
role for the dynamin GTPase in the
regulation of fusion pore expansion.
Mol Biol Cell 22:1907-1918.
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GENE LOOPING AND TRANSCRIPTION REGULATION
ATHAR ANSARI
Associate Professor
Office: 2115 BSB
Phone: 313-577-9251
Email: bb2749@ wayne.edu
Website: clasweb.clas.wayne.edu/
ansari
Ph.D., Biochemistry, University of
Delhi, 1993
Postdoctoral studies, University of
Medicine and Dentistry of New
Jersey, 1993-99
Adjunct Assistant Professor,
University of Medicine and Dentistry
of New Jersey, 2000-05
Assistant Professor,
University of Regina, 2005-06
Joined WSU faculty, 2006
The research in my lab is directed
toward understanding the regulation
of transcription in eukaryotes. The
prevailing view of the transcription of
eukaryotic protein encoding genes is
that RNA polymerase II transcribes a
linear template with spatially separate
promoter and terminator regions. We
use Chromosome Conformation Capture
(3C) technology to study promoterterminator interaction in budding
yeast (Saccharomyces cerevisiae). The
3C results clearly demonstrated that
promoter and terminator regions of a
gene interact during transcription such
that RNAP II transcribes a looped DNA
template rather than a linear one, as
shown in Figure 1. We have shown
that gene looping occurs only during
activated transcription and requires
transcription activators. The activator
facilitates interaction of promoter-bound
TFIIB with terminator-bound CPF and
CF1 3’end processing/termination
complexes. Accordingly, TFIIB, Ssu72,
Pta1, poly(A) polymerase and all the
subunits of CF1 complex contact both
the promoter and terminator regions of
a gene during activated transcription.
We were able to purify a holo-TFIIB
complex, which contains TFIIB and
termination factors. The holo-TFIIB
complex is believed to facilitate coupling
of termination to reinitiation in a looped
gene. Recently published results from
the lab show that promoter-bound
factors such as mediator are affecting
the termination of transcription, while
the terminator-bound CF1 complex is
influencing reinitiation of transcription
as well as promoter directionality, as
shown in Figure 1. We also showed
that the intron-mediated enhancement
of transcription occurs through gene
looping. Introns facilitate additional
physical interaction within a gene
(Figure 2). The role of splicing in
transcriptional regulation through gene
looping is an emerging new area of
research in my lab. Future research will
also focus on the role of TFIIH kinase
in promoter-terminator cross talk on
transcription termination. Attempts will
be made to determine if gene looping
confers promoter directionality on a
genome-wide scale. The role of mediator
complex and chromatin structure in the
process will also be investigated.
S E L E C T E D P U B L I C AT I O N S
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Al Husini N., Kudla P., Ansari A.
2013. A role for CF1A 3’ end
processing complex in promoterassociated transcription. PLoS Genet
9:e1003722.
Moabbi A.M., Agarwal N., El
Kaderi B., Ansari A. 2012. Role for
gene looping in intron-mediated
enhancement of transcription. Proc
Natl Acad Sci U S A 109:8505-8510.
Mukundan B., Ansari A. 2013. Srb5/
Med18-mediated termination of
transcription is dependent on gene
looping. J Biol Chem 288:1138411394.
Mukundan B., Ansari A. 2011.
Novel role for mediator complex
subunit Srb5/Med18 in termination
of transcription. J Biol Chem
286:37053-37057.
Medler S., Al Husini N.,
Raghunayakula S., Mukundan B.,
Aldea A., Ansari A. 2011. Evidence
for a complex of transcription factor
IIB with poly(A) polymerase and
cleavage factor 1 subunits required
for gene looping. J Biol Chem
286:33709-33718.
THE INFLUENCE OF MECHANICAL
FORCES ON CELL BEHAVIOR
Communication amongst mammalian
cells is imperative for proper function
and organization of any multicellular organism. Biochemical and
biomechanical signals are used by a
cell to determine whether it should
grow, divide, move or die. However,
our understanding of how mechanical
signals are delivered, received and
interpreted by mammalian cells is
poorly understood. In my laboratory,
we focus on how mechanical forces
are used in the processes of cellular
migration and invasion.
As a cell migrates, just as when we
walk, internal mechanical forces are
transferred externally to produce
forward movement. These forces on
the outside environment are referred to
as traction forces and can be measured
biophysically. When the force machinery
is experimentally manipulated, we can
begin to understand how these forces
are produced. Key cellular structures
in the production of this force include
the cytoskeleton and focal adhesion,
both highly dynamic, multi-protein
structures. We are currently studying
the formation and disassembly of these
structures and the effect on traction
force in the normal and cancerous
states. One important player we have
identified in the production of force
is the small subunit of the calciumdependent protease Calpain. We
currently have ongoing studies into this
mechanism.
Mechanical factors from the
extracellular environment can also
influence cellular functions. For
example, a cell can sense the stiffness
of its environment or may sense
tugging and pulling and respond
by altering its migration behavior.
We are interested in how these
external mechanical forces impact
the advancement of cancer. There are
multiple stages in cancer progression
in which mechanical factors could play
a significant role. For instance, the
matrix surrounding a tumor becomes
quite dense and mechanically rigid as
a tumor grows and has been shown
to contribute to the progression of the
disease. Furthermore, non-cancerous
cells in the tumor microenvironment
possess enhanced contractility and
actively remodel the extracellular
matrix surrounding the tumor, likely
producing mechanical forces by
tugging and pulling on fibers that
can be sensed by the tumor cells. We
have found that these tugging forces
significantly enhance the invasiveness
of cancer cells, and we have identified
a subset of genes whose expression is
altered in response to the mechanical
stimulation. Our laboratory is currently
pursuing the mechanistic pathways
responsible for the mechanically
enhanced invasion of cancer cells.
KAREN A. BENINGO
Associate Professor
Office: 2111 BSB
Phone: 313-577-6819
Email: beningo@biology.biosci.
wayne.edu
Website: clasweb.clas.wayne.edu/
beningo
Ph.D., Cell, Developmental and
Neutral Biology, University of
Michigan, 1998
NRSA Postdoctoral Fellow, University
of Massachusetts, 1998-2004
Research Assistant Professor,
University of Massachusetts, 2004-05
Joined WSU faculty, 2005
S E L E C T E D P U B L I C AT I O N S
Indra I., Beningo K.A. 2011. An
in vitro correlation of metastatic
capacity, substrate rigidity, and
ECM composition. J Cell Biochem
112:3151-3158.
Menon S., Kang C.M., Beningo
K.A. 2011. Galectin-3 secretion
and tyrosine phosphorylation is
dependent on the calpain small
subunit, Calpain 4. Biochem Biophys
Res Commun 410:91-96.
Menon S., Beningo K.A. 2011. Cancer
cell invasion is enhanced by applied
mechanical stimulation. PLoS One
6:e17277.
Indra I., Undyala V., Kandow C.,
Thirumurthi U., Dembo M., Beningo
K.A. 2011. An in vitro correlation of
mechanical forces and metastatic
capacity. Phys Biol 8:015015.
Undyala V., Dembo M., Cembrola
K., Perrin B.J., Huttenlocher A., Elce
J.S., Greer P.A., Wang Y-l., Beningo
K.A. 2008. The calpain small subunit
regulates cell-substrate mechanical
interactions during fibroblast
migration. J Cell Sci 121:3581-3588.
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EVOLUTIONARY AND CONSERVATION GENETICS
THOMAS E. DOWLING
We use a variety of markers (e.g.,
morphology, DNA sequences) to
examine the processes responsible
for the origin and maintenance of
organismal diversity. We have directed
our attention to the evolution of
cypriniform fishes (e.g., minnows,
suckers, etc.), one of the most diverse
orders of vertebrates in North America.
Our studies are specifically focused on
the process of speciation and the role
of hybridization and evolution. This is
being examined at three levels: factors
promoting population subdivision
and producing incipient species, the
evolution of reproductive isolation,
and the role of biogeography in the
evolution of species. Examination of
evolutionary patterns and processes
at these three levels of organization
provides a complete picture of
speciation in cypriniform fishes.
Because biodiversity of fishes is
declining, these approaches are applied
to understand the distribution of
genetic variation within and among
populations, providing valuable
information for the management of
various species facing extinction.
Professor
Office: 3113 BSB
Phone: 313-577-3020
Email: tdowling@wayne.edu
Website: clasweb.clas.wayne.edu/
cx9077
Ph.D., Biology, Wayne State
University, 1984
Postdoctoral Associate, University of
Michigan, 1984-88
Assistant Professor, 1988-1994
Associate Professor, 1994-99
Professor, 1999-2013
Arizona State University
Joined WSU faculty, 2013
S E L E C T E D P U B L I C AT I O N S
Dowling T.E., Turner T.F., Carson E.W.,
Saltzgiver M.J., Adams D., Kesner B.,
Marsh P.C. 2014. Time-series analysis
reveals genetic responses to intensive
management of razorback sucker
(Xyrauchen texanus). Evol Appl
7:339-354.
Unmack P.J., Hammer M.P., Adams
M., Johnson J.B., Dowling T.E.
2013. The role of continental shelf
width in determining freshwater
phylogeographic patterns in southeastern Australian pygmy perches
(Teleostei: Percichthyidae). Mol Ecol
22:1683-1699.
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Carson E.W., Tobler M., Minckley
W.L., Ainsworth R.J., Dowling
T.E. 2012. Relationships between
spatio-temporal environmental and
genetic variation reveal an important
influence of exogenous selection
in a pupfish hybrid zone. Mol Ecol
21:1209-1222.
Dowling T.E., Saltzgiver M.J., Adams
D., Marsh P.C. 2012. Assessment of
Genetic Variability in a Recruiting
Population of Endangered Fish,
the Razorback Sucker (Xyrauchen
texanus, Family Catostomidae), from
Lake Mead, AZ-NV. Transactions of
the American Fisheries Society 141:
990-999.
Dowling T.E., Saltzgiver M.J., Marsh
P.C. 2012. Genetic Structure Within
and Among Populations of the
Endangered Razorback Sucker
(Xyrauchen texanus) as Determined
by Analysis of Microsatellites.
Conservation Genetics 13, pp. 10731083.
EVOLUTION AND FUNCTION OF NEW GENES
IN PLANT GENOMES
New genes are defined as those recently
evolved in a specific lineage within a
short evolutionary time. It has been
well recognized that new genes play
an important role in the evolution of
genomes and organisms. Unlike other
eukaryotic genomes, plant genomes are
much more dynamic and generate new
genes at an exceptionally higher rate.
However, the fate-selection patterns
and functionalities of new plant genes
are generally not understood, and
therefore the cumulative impact of
new genes on plant genome evolution
is unknown. More importantly,
the rapid gene origination in plant
genomes provides an unprecedented
system we can study to determine
how new genes could shape the
evolution of genomes and organisms.
Fan Laboratory computationally and
experimentally analyzes the integrated
datasets to systematically determine the
divergent evolutionary processes and
functionalities of new plant genes. In
particular, Fan Laboratory
is using comparative
genomics, transcriptome,
evolution, epigenomics,
population genomics and
molecular biology-based
approaches to characterize
the origination, evolutionary
process and functionality
of new genes that
contributed to the genome
and organismal evolution in plant
species. Three research directions in
Fan Laboratory are accomplished. First,
transcriptom (RNA-seq, RT-PCR and
qRT-PCR) and methylome (BS-seq from
genome-wide DNA methylation) data
are used to decode the evolutionary
processes (conservation, sub- and
neo-functionalization) of new plant
genes. Second, evolutionary and
population genomics analyses are
used to determine evolutionary rates
and patterns of new plant genes.
Third, loss-of-function (e.g. T-DNA
mutagenesis and RNAi) analysis is
used to determine functionalities of
new plant genes. Our work ultimately
measures the origination rate and
evolutionary process of new genes and
their functionalities in plants. Our results
elucidate how quickly plants adapt to
changes in gene diversity, and to what
degree this is correlated with fitness
effects and environmental changes.
CHUANZHU FAN
Assistant Professor
Office: 5107.2 BSB
Phone: 313-577-6451
Email: cfan@wayne.edu
Website: fanlab.wayne.edu
Ph.D., North Carolina State
University, 2003
Postdoctoral Associate, University of
Chicago, 2004-2006
Assistant Research Scientist,
University of Arizona, 2007-2011
Joined WSU faculty, 2011
S E L E C T E D P U B L I C AT I O N S
Wang J., Marowsky N.C., Fan C.
2013. Divergent evolutionary and
expression patterns between lineage
specific new duplicate genes and
their parental paralogs in Arabidopsis
thaliana. PLoS One 8:e72362.
Zhang C., Wang J., Long M., Fan
C. 2013. gKaKs: the pipeline for
genome-level Ka/Ks calculation.
Bioinformatics 29:645-646.
Zhang C., Wang J., Marowsky N.C.,
Long M., Wing R.A., Fan C. 2013.
High occurrence of functional new
chimeric genes in survey of rice
chromosome 3 short arm genome
sequences. Genome Biol Evol
5:1038-1048.
Schnable P.S., Ware D., Fulton R.S.,
Stein J.C., Wei F., Pasternak S., Liang
C., Zhang J., Fulton L., Graves T.A.,
et al. 2009. The B73 maize genome:
complexity, diversity, and dynamics.
Science 326:1112-1115.
Fan C., Walling J.G., Zhang J., Hirsch
C.D., Jiang J., Wing R.A. 2011.
Conservation and purifying selection
of transcribed genes located in a rice
centromere. Plant Cell 23:2821-2830.
11
EVOLUTION OF INSECT VISION AND DEVELOPMENT
MARKUS FRIEDRICH
Professor
Office: 3117 BSB
Phone: 313-577-9612
Email: mf@biology.biosci.wayne.edu
Website: friedrichlab.googlepages.com
Ph.D., Zoology, University of Munich,
1995
Postdoctoral Scholar, California
Institute of Technology, 1996-99
Joined WSU faculty, 1999
While insects cannot read this page,
they track their visual environment
from the multifaceted perspective of
compound eyes in remarkable detail,
oftentimes with dramatically higher
resolution time than we do. Comprised
of several thousands of photosensitive
subunits called ommatidia, the
compound eyes of dragonflies or horse
flies, for instance, allow for the capture
of other insects in swift flight. Equally
remarkable is the fact that both the
function and development of insect
compound eyes involve the activity of
genes that are of similar importance for
the human camera eye. My laboratory
is studying the behavioral output,
organization and development of
insect visual systems to gain insight
into the evolution of vision in insects
and beyond.
Most of our
current work
revolves around
two beetle species.
This includes
the red flour
beetle Tribolium
castaneum, an
economically
important pest
as well as a widely studied laboratory
model. We deploy a variety of
approaches to study the development,
organization and function of the
Tribolium visual system, including
transcriptome-wide gene expression
analyses, gene knockdown by RNA
interference and video recording of
visual behavior in light/dark choice
tests. The long-term goals of these
efforts are to elucidate the molecular
evolution of insect vision genes
and understand how the genetic
regulation of eye development in
Tribolium compares to other animal
models, most importantly Drosophila.
Our second laboratory model is the
small carrion beetle Ptomaphagus
hirtus. This highly cave-adapted
species is endemic to the massive
cave system of Mammoth Cave
National Park in Kentucky. For
more than 100 years, P. hirtus was
considered physiologically blind. Our
transcriptomic, morphological and
behavioral investigations, however,
have shown that P. hirtus possesses a
highly reduced but functional vision.
Ongoing projects investigate the
evolutionary history, development,
sensitivity and behavioral significance
of the P. hirtus visual system in both
laboratory and field experiments.
S E L E C T E D P U B L I C AT I O N S
Friedrich M. 2013. Development
and Evolution of the Drosophila
Bolwig’s Organ: A Compound Eye
Relict. Molecular Genetics of Axial
Patterning. Growth and Disease in
the Drosophila Eye 329-357.
Friedrich M., Chen R., Daines
B., Bao R., Caravas J., Rai P.K.,
Zagmajster M., Peck S.B. 2011.
Phototransduction and clock gene
expression in the troglobiont beetle
Ptomaphagus hirtus of Mammoth
cave. J Exp Biol 214:3532-3541.
12
Bao R., Friedrich M. 2009. Molecular
evolution of the Drosophila
retinome: exceptional gene gain in
the higher Diptera. Mol Biol Evol
26:1273-1287.
Yang X., Weber M., Zarinkamar N.,
Posnien N., Friedrich F., Wigand B.,
Beutel R., Damen W.G., Bucher G.,
Klingler M., et al. 2009. Probing the
Drosophila retinal determination
gene network in Tribolium (II): The
Pax6 genes eyeless and twin of
eyeless. Dev Biol 333:215-227.
Tribolium Genome Sequencing
Consortium. 2008. The genome of
the model beetle and pest Tribolium
castaneum. Nature 452:949-955.
EVOLUTIONARY AND ECOLOGICAL ASPECTS OF
PLANT DEVELOPMENTAL GENETICS
What were the evolutionary steps that
occurred that led to this drastic change
in reproductive strategy? We utilize
cultivated spinach as a model organism
to answer such questions, and we are
using a variety of genetic, biochemical,
physiological and genomics approaches
to piece together a model for the
evolution of these complex traits.
The flower is an example of the
development of a revolutionary
morphology that leads to explosive
species diversity and ecological
dominance. The flower brings female
and male reproductive organs together
in a single structure, thereby increasing
reproductive success. Additionally, the
flower generates different reproductive
strategies by utilizing a variety of biotic
and abiotic polinators, and differing
times and presentations of mature
floral organs. One of the most extreme
examples of evolved reproductive
strategies is the recurrent development
of unisexual flowers derived from
hermaphroditic ancestral varieties. The
observation of unisexual flowers leads
to multiple basic questions: How is the
genetic cascade regulated to result
in flowers with only stamens or only
a gynoecium? What are the proteins
involved and how do they interact?
On an ecological scale, establishment
of new, highly successful invasive
species can drastically alter natural
communities. Invasive species are
invasive because they can out-compete
native species. Competitive advantages
can occur as a result of rapid growth
and reproduction, disproportionate
domination of limiting resources,
aggressive features that suppress
populations of native species, or
increased persistance and survivorship.
We are developing methods to
compromise the competitively
advantagious traits of specific invasive
plant species. Our goal is to generate
species-specific management
approaches that will not kill, but rather
control invasives and allow native
species to recolonize their native
communities. Our aims are to exploit
molecular genetic approaches to modify
the growth and reproduction of invasive
species within natural environments,
and thereby discover new methods for
environmental restoration.
EDWARD GOLENBERG
Professor and Associate Chair
Office: 2113 BSB
Phone: 313-577-2888
Email: golenberg@wayne.edu
Website: clasweb.clas.wayne.edu/
golenberg
Ph.D., Ecology and Evolution, SUNY
at Stony Brook University, 1986
BARD Postdoctoral Fellow,
Postdoctoral Visiting Geneticist,
University of California-Riverside,
1986-1990
Joined WSU faculty, 1990
S E L E C T E D P U B L I C AT I O N S
Golenberg E.M., West N.W. 2013.
Hormonal interactions and gene
regulation can link monoecy and
environmental plasticity to the
evolution of dioecy in plants. Am J
Bot 100:1022-1037.
Sather D.N., Jovanovic M., Golenberg
E.M. 2010. Functional analysis of
B and C class floral organ genes in
spinach demonstrates their role in
sexual dimorphism. BMC Plant Biol
10:46.
Diggle P.K., Di Stilio V.S., Gschwend
A.R., Golenberg E.M., Moore R.C.,
Russell J.R.W., Sinclair J.P. 2011. Multiple
developmental processes underlie sex
differentiation in angiosperms. Trends
in Genetics 27:368-376.
Golenberg E.M., Sather D.N., Hancock
L.C., Buckley K.J., Villafranco N.M.,
Bisaro D.M. 2009. Development of
a gene silencing DNA vector derived
from a broad host range geminivirus.
Plant Methods 5:9.
Sather D.N., Golenberg E.M. 2009.
Duplication of AP1 within the
Spinacia oleracea L. AP1/FUL clade
is followed by rapid amino acid
and regulatory evolution. Planta
229:507-521.
13
I. THE ROLE OF CARDIOLIPIN IN MITOCHONDRIAL
AND CELLULAR FUNCTION.
MIRIAM GREENBERG
Professor
Office: 4178.2 BSB
Phone: 313-577-5202
Email: mgreenberg@wayne.edu
Website: clasweb.clas.wayne.edu/
mgreenberg
Ph.D., Genetics, Albert Einstein
College of Medicine, 1980
Postdoctoral Fellow, Damon RunyonWalter Winchell Cancer Fund, Harvard
University, 1980-85
Assistant Professor, University of
Michigan, 1986-1992
Joined WSU faculty, 1993
We are using yeast and mammalian
cell culture models to understand the
mitochondrial and cellular functions
of the ubiquitous phospholipid
cardiolipin (CL). We identified the
first yeast CL mutant (crd1Δ), and we
developed the yeast model (taz1Δ)
for Barth syndrome (BTHS), a lifethreatening cardiomyopathy resulting
from perturbation of CL remodeling
(changing CL fatty acyl composition).
We have shown that CL is required for
optimal mitochondrial bioenergetics
and for essential cellular functions,
including mitochondrial protein
import, mitochondrial fusion, iron
homeostasis and vacuolar function.
Our current studies address the
following questions: 1. How does
CL regulate metabolism? 2. How
does CL deficiency perturb cellular
functions? 3. What is the function
of CL remodeling? This knowledge
may lead to the development of
new treatments for BTHS and other
CL-associated disorders, including
diabetic cardiomyopathy, heart failure
and ischemia/reperfusion injury.
II. MOLECULAR TARGETS OF
BIPOLAR DISORDER DRUGS.
Bipolar disorder (BD) is a chronic,
debilitating illness affecting one to two
percent of the population. Lithium and
valproate are currently used to treat BD,
but neither drug is completely effective,
and their therapeutic mechanisms are
not understood. Elucidation of the
therapeutic mechanisms will greatly
facilitate the development of new
therapies to treat BD. To this end, we are
pursuing genetic, biochemical, lipidomic
and cell biological approaches to test
the hypothesis that inositol depletion
leads to defects in vacuolar function and
V-ATPase activity. In synaptic vesicles,
V-ATPase activity drives the uptake of
neurotransmitters. Our current studies
address the following questions using
yeast and human cell culture: 1. What
is the mechanism underlying valproatemediated inhibition of inositol synthesis?
2. How does inositol depletion lead to
perturbation of vacuolar function? 3.
Does perturbation of the V-ATPase by
valproate affect neurotransmission?
S E L E C T E D P U B L I C AT I O N S
Raja V., Greenberg M.L. 2014. The
functions of cardiolipin in cellular
metabolism-potential modifiers of
the Barth syndrome phenotype.
Chem Phys Lipids 179:49-56.
Ye C., Lou W., Li Y., Chatzispyrou I.A.,
Huttemann M., Lee I., Houtkooper
R.H., Vaz F.M., Chen S., Greenberg M.L.
2014. Deletion of the cardiolipin-specific
phospholipase Cld1 rescues growth and
life span defects in the tafazzin mutant:
implications for Barth syndrome. J Biol
Chem 289:3114-3125.
14
Deranieh R.M., He Q., Caruso
J.A., Greenberg M.L. 2013.
Phosphorylation regulates myoinositol-3-phosphate synthase: a
novel regulatory mechanism of
inositol biosynthesis. J Biol Chem
288:26822-26833.
Patil V.A., Fox J.L., Gohil V.M., Winge
D.R., Greenberg M.L. 2013. Loss
of cardiolipin leads to perturbation
of mitochondrial and cellular iron
homeostasis. J Biol Chem 288:16961705.
Ye C., Bandara W.M., Greenberg
M.L. 2013. Regulation of inositol
metabolism is fine-tuned by inositol
pyrophosphates in Saccharomyces
cerevisiae. J Biol Chem 288:2489824908.
UNDERSTANDING THE CONFRONTATION BETWEEN
HSV-1 VIRUS AND HOST ANTIVIRAL DEFENSES
has been implicated in multiple cell
regulatory pathways such as apoptosis,
cell senescence, DNA damage
response and antiviral defense. The
degradation of PML by ICP0 during
HSV-1 infection affects the ultimate
productivity of the virus. Ongoing
projects in my lab focus on dissecting
the domains of ICP0 important for
PML degradation, and delineating
how ICP0 modification and subcellular
localization of ICP0 affect ICP0 E3
ubiquitin ligase activity. From there
we seek to investigate the multiple
functions of ICP0, in addition to
degrading cellular defensive proteins,
and the cooperation among ICP0 and
other viral proteins in subjugating host
defenses. We hope the outcome of our
studies will advance our knowledge
of virus-host interaction and provide
pivotal information for developing new
strategies of herpes treatments.
With limited genetic materials, viruses
are able to overcome multiple layers of
host defenses and subjugate the host
in infection. Understanding how viruses
employ multifunctional viral proteins
to target different cell machineries is
one of the main objectives in virology
research. It provides critical information
for designing novel antiviral treatment.
My lab is interested in understanding
the biology of cellular antiviral defense
systems and how herpes simplex virus
1 (HSV-1) overcomes these defenses
to establish infection. Our current
focus is an immediate early viral
protein called ICP0, a multifunctional
protein that contains an E3 ubiquitin
ligase activity and degrades multiple
cellular proteins restrictive to viral
expression. One of the cell-intrinsic
defenses targeted by ICP0 involves
a tumor repressor protein named
promyelocytic leukemia (PML), which
SP100
S
S
S
PML
Rapid Entry
ICP0
SP100
S
S
S
PML
S
S
ND10
ND10
Fusion
S
SP100
S
PML
∆C
Rapid Entry
S
S
SP100
S
S
S
ND10
PML
S
ICP0
∆C
d
ate
ler
ce ing
Ac ycl
C
S
∆C
S
S
S
ND10
R
∆ES
Release
PML degradation
without retention
S
S
S
S
SP100
S
S
R
PML
Daxx
SP100
PML
Daxx
S
S
ND10
S
S
S
Fusion
Surface
Interaction
S
S
S
Joined WSU faculty, 2011
S
S
S
Postdoctoral Fellow, University of
Chicago, 2011
S
Dispersal of ND10
components
ICP0
Ph.D., Biochemistry ,Ohio State
University, 2001
ND10
Adhesion
C.
S
S
Office: 4115 BSB
Phone: 313-577-6402
Email: ex3288@wayne.edu
Website: clasweb.clas.wayne.edu/
ex3288
Retention
S
S
Daxx
S
Daxx
S
S
Assistant Professor
S
S
S
PML and Sp100
degradation
ICP0
Adhesion
B.
S
S
S
S S S
Daxx
S
Daxx
S
Daxx
S
S
Daxx
A.
HAIDONG GU
ND10
∆ES
S
S
No degradation
of PML
Adhesion
S E L E C T E D P U B L I C AT I O N S
Gu H., Zheng Y., Roizman B. 2013.
Interaction of herpes simplex virus
Figure 9
ICP0 with ND10 bodies: a sequential
process of adhesion, fusion, and
retention. J Virol 87:10244-10254.
Zerboni L., Che X., Reichelt M., Qiao
Y., Gu H., Arvin A. 2013. Herpes
simplex virus 1 tropism for human
sensory ganglion neurons in the
severe combined immunodeficiency
mouse model of neuropathogenesis.
J Virol 87:2791-2802.
Gu H., Roizman B. 2009. The two
functions of herpes simplex virus 1
ICP0, inhibition of silencing by the
CoREST/REST/HDAC complex and
degradation of PML, are executed in
tandem. J Virol 83:181-187.
Gu H., Poon A.P., Roizman B. 2009.
During its nuclear phase the
multifunctional regulatory protein
ICP0 undergoes proteolytic cleavage
characteristic of polyproteins. Proc
Natl Acad Sci U S A 106:19132-19137.
Gu H., Roizman B. 2007. Herpes
simplex virus-infected cell protein
0 blocks the silencing of viral DNA
by dissociating histone deacetylases
from the CoREST-REST complex.
Proc Natl Acad Sci U S A 104:1713417139.
15
HOMOLOGOUS RECOMBINATION
IN ASEXUAL GENOMES
WEILONG HAO
Assistant Professor
Office: 5107.1 BSB
Phone: 313-577-6450
Email: haow@wayne.edu
Website: haolab.wayne.edu
Ph.D., Computational Biology,
McMaster University, 2007
Postdoctoral Fellow, Indiana
University, 2007-10
NSERC Postdoctoral Fellow,
University of Toronto, 2010-11
Joined WSU faculty, 2011
Our primary research interest is to
develop a better understanding of the
alterations of genome architecture
by homologous recombination
and their corresponding functional
consequences. Our research has
recently developed in two model
systems: the human pathogenic
bacterium Neisseria meningitides and
mitochondrial genomes in eukaryotes,
both of which are highly dynamic in
genome architecture. We are currently
investigating genomic variation and
its association with epidemiology
in Neisseria meningitides using both
the whole genome sequences and
transcriptome data. Our findings have
shown that homologous
recombination, not
mutation, resulted in
extensive sequence diversity
and gene content variation
among N. meningitides
strains with identical
multilocus sequence typing
(MLST) types. The analysis
on a variety of clinical
isolates of a single MLST
type further showed that
homologous recombination
between distantly related
strains is the main driving
force in the evolution
100
of the N. meningitides
epidemiology at a real-time scale. We
have also observed an unexpectedly
high frequency of homologous
recombination in the mitochondrial
genome between different yeast
species. Homologous recombination
is responsible not only for sequence
diversity and the chimeric protein
coding genes, but also for the high
intron mobility. Knowing the high
recombination frequency in the
mitochondrial genomes, we plan to
take advantage of the well-developed
yeast genetic tools and investigate the
functional consequences (e.g., fitness,
aging and fertility) of homologous
recombination.
Anneslea
Ternstroemia stahlii
Ternstroemia gymnanthera
Cleyera
86 mya
Eurya
Pentaphylax
Rhododendron
Empetrum
Vaccinium
Enkianthus
Cyrilla
Fouquieria
0 mya
S E L E C T E D P U B L I C AT I O N S
Wu B., Hao W. 2014. Horizontal
transfer and gene conversion as an
important driving force in shaping
the landscape of mitochondrial
introns. G3 (Bethesda) 4:605-612.
Kong Y., Ma J.H., Warren K., Tsang R.S.,
Low D.E., Jamieson F.B., Alexander
D.C., Hao W. 2013. Homologous
recombination drives both sequence
diversity and gene content variation in
Neisseria meningitidis. Genome Biol
Evol 5:1611-1627.
16
Hao W., Ma J.H., Warren K., Tsang
R.S., Low D.E., Jamieson F.B.,
Alexander D.C. 2011. Extensive
genomic variation within clonal
complexes of Neisseria meningitidis.
Genome Biol Evol 3:1406-1418.
Hao W., Richardson A.O., Zheng Y.,
Palmer J.D. 2010. Gorgeous mosaic
of mitochondrial genes created
by horizontal transfer and gene
conversion. Proc Natl Acad Sci U S A
107:21576-21581.
Hao W., Palmer J.D. 2009. Finescale mergers of chloroplast
and mitochondrial genes create
functional, transcompartmentally
chimeric mitochondrial genes. Proc
Natl Acad Sci U S A 106:1672816733.
MYXOCOCCUS XANTHUS
DEVELOPMENTAL BIOLOGY
The research interests in our group
include those that have fascinated
development biologists for ages.
What are the regulatory mechanisms
that segregate cells into distinct
developmental fates? What molecular
mechanisms drive cell morphogenesis?
What signalling strategies are employed
to regulate complex behavior? How
are individual regulatory pathways
integrated into to a signalling network?
Our model organism, Myxococcus
xanthus, is a bacterium renowned for
its fascinating multicellular behaviors.
During growth, M. xanthus swarms
feed on prey microorganisms, but
when nutrients become limiting, they
enter a developmental program in
which cells segregate into distinct fates
such as fruiting body formation and
sporulation, programmed cell death,
and formation of a persister-like state.
phosphorelay signalling family,
including an unusual four-component
system and inter/intra phosphotransfer
between histidine kinase proteins. Our
long-term goal is to define and model
the integrated signalling network that
controls cell fate segregation during
M. xanthus development.
Another focus in our group is
investigation of the unique spore
differentiation process in M. xanthus.
Spore differentiation involves
rearrangement of the entire rodshaped cell into a spherical spore. We
are currently focusing on the protein
machinery necessary for synthesis and
assembly of the spore coat on the
surface of the outer membrane.
PENELOPE HIGGS
Assistant Professor
Office: 4156 BSB
Phone: 313-577-9241
Email: pihiggs@wayne.edu
Website: clasweb.clas.wayne.edu/
pihiggs
Ph.D., Molecular Biosciences,
Washington State University, 2001
Postdoctoral Fellow, University of
California, Berkeley, 2001-05
One aspect of our research involves
defining the regulatory mechanisms
that drive segregation of M. xanthus
cells into the distinct developmental
fates. We have identified a series of
atypical signalling proteins necessary
for appropriate cell fate segregation.
Our genetic and biochemical analyses
have defined novel signal flow in
members of histidine aspartate
Research Group Leader, Max Planck
Institute for Terrestrial Microbiology,
2005-2013
Joined WSU faculty, 2013
S E L E C T E D P U B L I C AT I O N S
Higgs P.I., Hartzell P.L., Holkenbrink C.,
Hoiczyk E. 2014. Myxococcus xanthus
vegetative and developmental cell
heterogeneity. In Myxobacteria:
Genomics and Molecular Biology.
Yang, Z. and Higgs, P.I. (ed.) Horizon
Scientific Press, Norfolk, UK.
Lee B., Holkenbrink C., Treuner-Lange
A., Higgs P.I. 2012. Myxococcus
xanthus developmental cell
fate production: heterogeneous
accumulation of developmental
regulatory proteins and reexamination
of the role of MazF in developmental
lysis. J Bacteriol 194:3058-3068.
Muller F.D., Schink C.W., Hoiczyk
E., Cserti E., Higgs P.I. 2012. Spore
formation in Myxococcus xanthus
is tied to cytoskeleton functions and
polysaccharide spore coat deposition.
Mol Microbiol 83:486-505.
Schramm A., Lee B., Higgs P.I.
2012. Intra- and interprotein
phosphorylation between two-hybrid
histidine kinases controls Myxococcus
xanthus developmental progression. J
Biol Chem 287:25060-25072.
Muller F.D, Treuner-Lange A., Heider
J., Huntley S.M., Higgs P.I. 2010.
Global transcriptome analysis of
spore formation in Myxococcus
xanthus reveals a locus necessary for
cell differentiation. BMC Genomics
11:264.
17
ROLES OF DISTURBANCES IN
TERRESTRIAL ECOSYSTEMS
DAN KASHIAN
Associate Professor
Office: 3107 BSB
Phone: 313-577-9093
Email: dkash@wayne.edu
Website: clasweb.clas.wayne.edu/
dankashian
Ph.D., Zoology/Forest Ecology
and Management, University of
Wisconsin, 2002
Postdoctoral Associate, Colorado
State University, 2003-06
Joined WSU faculty, 2006
Terrestrial systems are always
changing as the result of some past
or present disturbance. Disturbances
may be a short, distinct event in time
or a gradual, continuous process; a
devastating, widespread episode or
one that creates only subtle changes
in a small area; an episode thought
to be in sync with nature; or a strictly
human influence. These disturbances
and the successional processes
that follow them are ubiquitous,
and therefore are critical drivers of
terrestrial ecosystems. Understanding
how natural disturbances such
as wildfires, insect outbreaks or
windstorms — as well as human
disturbances such as varying land
use and the introduction of invasive
species — change the structure and
function of terrestrial ecosystems
may underlie the future of ecology.
Even as climate change may be the
most widespread threat to natural
ecosystems, it is the ability of climate
change to alter disturbance regimes
over the next century that will likely
create the quickest and most extensive
changes in terrestrial ecosystem
composition and structure.
well as the influence of disturbances
in shaping the distribution and spatial
heterogeneity of terrestrial plant
communities and ecosystems. Much
of my work is aimed at understanding
how the combination of site
factors, biotic interactions, natural
disturbances and humans affect
landscape patterns and ecosystem
processes in forests. I am particularly
interested in how changing climate
has and will affect the processes that
shape disturbance dynamics, and
the interaction of disturbances that
control plant community distribution,
structure and function, especially in
forests. Nearly all of my research has
been field-based, supplemented by
GIS, remote sensing and simulation
modeling. My study sites include the
Front Range of Colorado; Yellowstone
National Park and the national forests
that surround it; northern Minnesota;
northern lower and eastern upper
Michigan; and Southeast Michigan.
My research centers on the
community, ecosystem and landscape
ecology of terrestrial ecosystems, as
S E L E C T E D P U B L I C AT I O N S
18
Kashian D.M., Romme W.H., Tinker
D.B., Turner M.G., Ryan M.G.
2013. Postfire changes in forest
carbon storage over a 300-year
chronosequence of Pinus contortadominated forests. Ecological
Monographs 83:49-66.
Hicke J.A., Allen C.D., Desai A.R., Dietze
M.C., Hall R.J., Hogg E.H., Kashian
D.M., Moore D., Raffa K.F., Sturrock
R.N., et al. 2012. Effects of biotic
disturbances on forest carbon cycling
in the United States and Canada.
Global Change Biology 18:7-34.
Kashian D.M., Corace R.G., Shartell
L.M., Donner D.M., Huber P.W. 2012.
Variability and persistence of postfire biological legacies in jack pinedominated ecosystems of northern
Lower Michigan. Forest Ecology and
Management 263:148-158.
Kashian D.M., Jackson R.M., Lyons
H.D. 2011. Forest structure altered
by mountain pine beetle outbreaks
affects subsequent attack in a
Wyoming lodgepole pine forest,
USA. Canadian Journal of Forest
Research 41:2403-2412.
Kashian D.M., Witter J.A. 2011.
Assessing the potential for ash
canopy tree replacement via current
regeneration following emerald
ash borer-caused mortality on
southeastern Michigan landscapes.
Forest Ecology and Management
261:480-488.
THE ROLE OF DISTURBANCE IN
FRESHWATER SYSTEMS
My lab focuses on the effects of
disturbance, including invasive
species, climate change and
contaminants, on aquatic
communities and freshwater
ecosystems. Our work examines
interactions among organisms,
the environment and humans,
emphasizing multidisciplinary
collaborations to address complex
environmental issues. Through
basic and applied research, we
use aquatic organisms as sentinels
of human and environmental
health hazards to further our
understanding of disturbances in
the environment. I am particularly
interested in developing new
methods and tools, both physical
and mathematical, to improve
water quality monitoring, as well as
quantifying the effects of multiple
stressors on the environment. This
includes evaluating the potential for
contaminants to facilitate invasion
by exotic species. We are developing
a biomarker assay to evaluate
oxidative stress in invasive dreissenid
mussels (zebra and quagga) exposed
to polychlorinated biphenyls — a
class of persistent organic pollutants.
Through this work, we have
documented sensitivity differences
between these two closely related
species that may help explain, in
part, a mechanism by which quagga
mussels have a competitive edge
over zebra mussels. Furthermore,
our lab is developing a novel multilife history stage bioassay using
invasive dreissenid mussels to
evaluate chemical toxicity in the
environment. The early life stage
of zebra mussels is planktonic and
exposed to chemicals dissolved
in the water column. In contrast,
the adults are sessile and generally
benthic, thus exposed to sedimentbound chemicals. This multi-stage
life history bioassay may allow a
more comprehensive evaluation
of toxicity in freshwater systems.
Additionally, we are developing
and testing methods for mapping
cumulative risks from multiple
vectors of aquatic invasive species to
prioritize monitoring and prevention
strategies. This project will yield
active monitoring strategies for
high-risk areas and high-efficiency
sampling protocols. My research
tests what is commonly accepted
and pushes the boundaries to
improve upon traditional methods
to be more protective of both
environmental and human health.
DONNA KASHIAN
Associate Professor
Office: 3115 BSB
Phone: 313-577-8052
Email: dkashian@wayne.edu
Website: clasweb.clas.wayne.edu/
dkashian
Ph.D., Zoology, University of
Wisconsin, 2002
Postdoctoral Associate, Colorado
State University, 2002-06
Joined WSU faculty, 2009
S E L E C T E D P U B L I C AT I O N S
Vijayavel K., Sadowsky M.J.,
Ferguson J.A., Kashian D.R. 2013.
The establishment of the nuisance
cyanobacteria Lyngbya wollei in Lake
St. Clair and its potential to harbor
fecal indicator bacteria. Journal of
Great Lakes Research 39:560-568.
Gronewold A.D., Stow C.A., Vijayavel
K., Moynihan M.A., Kashian D.R.
2013. Differentiating Enterococcus
concentration spatial, temporal, and
analytical variability in recreational
waters. Water Research 47:21412152.
Burtner A.M., McIntyre P.B., Allan J.D.,
Kashian D.R. 2011. The influence
of land use and potamodromous
fish on ecosystem function in Lake
Superior tributaries. Journal of Great
Lakes Research 37:521-527.
Kashian D.R., Zuellig R.E., Mitchell
KA, Clements WH. 2007. The cost
of tolerance: sensitivity of stream
benthic communities to UV-B and
metals. Ecol Appl 17:365-375.
Clements W.H., Brooks M.L., Kashian
D.R., Zuellig R.E. 2008. Changes in
dissolved organic material determine
exposure of stream benthic
communities to UV-B radiation
and heavy metals: implications for
climate change. Global Change
Biology 14:2201-2214.
19
EPIGENETICS OF GENE EXPRESSION
IN DROSOPHILA
VICTORIA MELLER
Professor
Office: 2119 5107.1 BSB
Phone: 313-577-3451
Email: av3459@wayne.edu
Website: clasweb.clas.wayne.edu/
meller
Ph.D., Biology, University of North
Carolina, 1990
Postdoctoral studies, SUNY Stony
Brook, 1990-93
Postdoctoral studies, Cold Spring
Harbor Laboratories, 1993
Postdoctoral studies, Baylor College
of Medicine, 1993-97
Joined WSU faculty, 2004
Differential gene regulation underlies
most cellular processes. In some
instances, an entire chromosome
is subject to coordinate regulation.
This is a common property of sex
chromosomes. For example, male
fruit flies (Drosophila melanogaster)
have a single X-chromosome, but
females carry two X-chromosomes. To
correct for the resulting imbalance in
the dose of X-linked gene products,
Drosophila males transcribe their
X-chromosome at twice the rate
that females do — a process termed
dosage compensation. A complex of
proteins orchestrates transcriptional
up-regulation. These proteins bind
selectively to the male X-chromosome,
where they alter chromatin structure
and chemistry. These changes are
ultimately responsible for enhanced
transcription.
The non-coding roX1 and roX2
RNAs (RNA on the X) participate in
formation of the complex, and can
be observed binding along the length
of the X-chromosome. When both
roX genes are mutated, the proteins
that normally assemble with these
RNAs fail to localize exclusively to the
X-chromosome. The resulting failure
of transcriptional up-regulation is
lethal to males. We investigate sexspecific chromatin regulation and are
particularly interested in how the roX
RNAs direct epigenetic modifications
to specific regions. Although the roX
RNAs have a role in identification of
X chromatin, we recently discovered
that a small RNA pathway also
contributes to this process. Our
working model is that selective
identification of X chromatin involves
cooperation between the small RNA
pathway and the roX genes.
A contrasting regulatory process
occurs in mammalian females, where
dosage compensation is achieved by
silencing a single X-chromosome.
Interestingly, a large noncoding
RNA produced by the Xist gene (X
inactive-specific transcript) is required
for silencing and can be observed
coating the silent X-chromosome.
Furthermore, small RNA pathways
have been implicated in mammalian
dosage compensation. This surprising
convergence suggests that similar
molecular principles underlie the
modulation of large chromosomal
domains in flies and mammals.
S E L E C T E D P U B L I C AT I O N S
Apte M.S., Moran V.A., Menon D.U.,
Rattner B.P., Barry K.H., Zunder
R.M., Kelley R., Meller V.H. 2014.
Generation of a useful roX1 allele
by targeted gene conversion. G3
(Bethesda) 4:155-162.
Menon D.U., Meller V.H. 2012. A
role for siRNA in X-chromosome
dosage compensation in Drosophila
melanogaster. Genetics 191:10231028.
20
Apte M.S., Meller V.H. 2012.
Homologue pairing in flies and
mammals: gene regulation when
two are involved. Genet Res Int
2012:430587.
Menon D.U., Meller V.H. 2009.
Imprinting of the Y chromosome
influences dosage compensation in
roX1 roX2 Drosophila melanogaster.
Genetics 183:811-820.
Deng X., Meller V.H. 2008.
Molecularly severe roX1 mutations
contribute to dosage compensation
in Drosophila. Genesis 47:49-54.
NEUROCHEMISTRY OF OXIDATIVE STRESS
Many degenerative conditions,
including Parkinson’s, Alzheimer’s,
cardiovascular disease and even aging
itself are attributed at least in part
to oxidative stress. Oxidative stress
is a vague concept based largely
on observation of the products of
oxidation rather than the process. My
laboratory is studying redox cycling
of important biological compounds in
an effort to discover general principles
and approaches widely applicable to
understanding oxidative stress in its
many pathological manifestations. We
are particularly interested in dopamine
oxidation products because these
may be responsible for the death of
dopaminergic neurons, which is the
cause of Parkinson’s disease. We have
found that hypochlorite produced
by myeloperoxidase reacts with the
dopamine oxidation product cysteinyldopamine and converts it into a
compound that redox cycles. Redox
cycling occurs when a compound is
reduced either chemically by ascorbic
acid or enzymatically by mitochondria
in the presence of NADH. The reduced
compound then reacts spontaneously
with O2 to generate superoxide and
hydrogen peroxide (H2O2). These
reactive oxygen species would be
expected to damage mitochondria
leading to mitochondrial dysfunction.
Moreover, these reactive oxygen
species promote both dopamine
oxidation and hypochlorite
production, making redox cycling
autocatalytic. I hypothesize, therefore,
that hypochlorite produced by
microglial myeloperoxidase creates
redox cycling compounds that lead to
oxidative stress and the consequent
death of dopaminergic neurons in
Parkinson’s disease. We are testing
this hypothesis and exploring the
destructive effects of oxidative
stress using the dopamine oxidation
products we have synthesized and
similar redox cycling compounds.
Our experimental approaches range
from organic and electrochemistry to
biochemistry and cell biology.
DAVID L. NJUS
Professor
Office: 2125 BSB
Phone: 313-577-3105
Email: dnjus@wayne.edu
Website: bio.wayne.edu/profhtml/
njus/njus.html
Ph.D., Biophysics, Harvard University,
1975.
Postdoctoral studies, University of
Oxford, 1975-78.
Joined WSU faculty, 1978
S E L E C T E D P U B L I C AT I O N S
Alhasan R., Njus D. 2008. The
epinephrine assay for superoxide:
why dopamine does not work. Anal
Biochem 381:142-147.
Li G., Zhang H., Sader F., Vadhavkar
N., Njus D. 2007. Oxidation of
4-methylcatechol: implications for
the oxidation of catecholamines.
Biochemistry 46:6978-6983.
Barber M., Njus D. 2007. Clicker
evolution: seeking intelligent design.
CBE Life Sci Educ 6:1-8.
Njus D., Wigle M., Kelley P.M., Kipp
B.H., Schlegel H.B. 2001. Mechanism
of ascorbic acid oxidation by
cytochrome b(561). Biochemistry
40:11905-11911.
Kipp B.H., Kelley P.M,. Njus D. 2001.
Evidence for an essential histidine
residue in the ascorbate-binding site
of cytochrome b561. Biochemistry
40:3931-3937.
21
CHROMATIN STRUCTURE
AND GENE TRANSCRIPTION
LORI PILE
Associate Professor
Office: 4111 BSB
Phone: 313-577-9104
Email: loripile@wayne.edu
Website: clasweb.clas.wayne.edu/
PileLaboratory
Ph.D., Molecular Genetics,
Biochemistry and Microbiology,
University of Cincinnati Medical
School, 1998
Postdoctoral Fellow, National
Institutes of Health, 1998-2003
Joined WSU faculty, 2004
Misregulation of gene expression
is a major cause of human
disease, including cancer and
neurodegenerative disorders. If
genes are not expressed correctly,
the normal function of a cell will be
altered. This may result in excess cell
division leading to cancerous tumors,
no cell growth resulting in cell loss, or
premature differentiation resulting in
non-functioning cells. Coordinating
spatial and temporal regulation
of gene expression is essential for
normal development.
Gene expression is regulated in part
by the interactions of genomic DNA
with the packaging histone proteins.
Research in the Pile laboratory is
directed toward understanding how
genome packaging affects gene
expression. Histones undergo a
variety of modifications, including
acetylation, phosphorylation and
methylation, which in turn affect the
level of packaging. We are currently
investigating how the SIN3 histonemodifying complex functions to
repress transcription at the epigenetic
level. SIN3 is required for viability of
multicellular organisms, and mutations
in components in the complex have
been linked to defects in cell cycle
progression. Current objectives of
the lab are to understand regulatory
pathways that affect SIN3 expression
and activity, and to understand the
consequences of SIN3 recruitment at
target genes. We are taking a multipronged approach to address these
questions in the model organism
Drosophila melanogaster. We are
utilizing a combination of biochemical,
molecular and genetic techniques to
understand the mechanism of SIN3
gene regulation. Data from these
studies will help to elucidate the
contribution of histone modification to
signaling cascades that impact cellular
decisions critical for proliferation,
development and viability.
S E L E C T E D P U B L I C AT I O N S
22
Swaminathan A., Barnes V.L., Fox
S., Gammouh S., Pile L.A. 2012.
Identification of Genetic Suppressors
of the Sin3A Knockdown Wing
Phenotype. PLoS One 7:e49563.
Barnes V.L., Strunk B.S., Lee I.,
Huttemann M., Pile L.A. 2010. Loss of
the SIN3 transcriptional corepressor
results in aberrant mitochondrial
function. BMC Biochem 11:26.
Swaminathan A., Gajan A., Pile L.A.
2012. Epigenetic regulation of
transcription in Drosophila. Front
Biosci 17:909-937.
Spain M.M., Caruso J.A., Swaminathan
A., Pile L.A. 2010. Drosophila SIN3
isoforms interact with distinct proteins
and have unique biological functions.
J Biol Chem 285:27457-27467.
Swaminathan A., Pile L.A. 2010.
Regulation of cell proliferation and
wing development by Drosophila SIN3
and String. Mech Dev 127:96-106.
INSECT COMPARATIVE GENETICS
AND DEVELOPMENT
The origins and diversification of
morphological novelties is a central
question in biology. The main focus
of my research program is the
elucidation of the developmental and
genetic mechanisms that govern such
morphological changes in nature.
In particular, we are interested in
understanding how the divergence
of insect body plans have facilitated
the radiation and adaptation of this
most numerous animal group to
almost every possible environmental
and ecological condition. The
understanding of the genetic basis
of this phenotypic variation is not
only of fundamental importance
(What are the general and speciesspecific details of animal body
development?), but also has an
increasingly significant practical value
in designing novel approaches for
insect control and management. Our
research endeavors address a broad
range of questions, from the origin of
insect wings and body pigmentation
to the mechanisms governing the
development of the pollen gathering
apparatus basket in honeybees. To
tackle these issues, we employ a
highly integrative approach, which
combines tools and perspectives from
developmental biology, genomics and
molecular genetics.
ALEKSANDAR POPADIĆ
Associate Professor
Office: 3119 BSB
Phone: 313-577-9537
Email: apopadic@biology.biosci.
wayne.edu
Website: bio.wayne.edu/profhtml/
popadic/popadic.html
Ph.D., University of Georgia, 1994
Howard Hughes Postdoctoral Fellow,
Indiana University, 1995-99
Joined WSU faculty, 1999
S E L E C T E D P U B L I C AT I O N S
Turchyn N., Chesebro J., Hrycaj
S., Couso J.P., Popadic A. 2011.
Evolution of nubbin function
in hemimetabolous and
holometabolous insect appendages.
Dev Biol 357:83-95.
Chen B., Hrycaj S., Schinko J.B.,
Podlaha O., Wimmer E.A., Popadic
A., Monteiro A. 2011. Pogostick: a
new versatile piggyBac vector for
inducible gene over-expression and
down-regulation in emerging model
systems. PLoS One 6:e18659.
Kirkness E.F., Haas B.J., Sun W., Braig
H.R., Perotti M.A., Clark J.M., Lee
S.H., Robertson H.M., Kennedy
R.C., Elhaik E., et al. 2010. Genome
sequences of the human body
louse and its primary endosymbiont
provide insights into the permanent
parasitic lifestyle. Proc Natl Acad Sci
U S A 107:12168-12173.
Chesebro J., Hrycaj S., Mahfooz N.,
Popadic A. 2009. Diverging functions
of Scr between embryonic and
post-embryonic development in a
hemimetabolous insect, Oncopeltus
fasciatus. Dev Biol 329:142-151.
Hrycaj S., Mihajlovic M., Mahfooz
N., Couso J.P., Popadic A. 2008.
RNAi analysis of nubbin embryonic
functions in a hemimetabolous
insect, Oncopeltus fasciatus. Evol
Dev 10:705-716.
23
OLFACTORY SYSTEM IN MOSQUITO,
AEDES AEGYPTI
ANN SODJA
Associate Professor
Office: 3105 BSB
Phone: 313-577-2908
Email: asodja@biology.biosci.wayne.
edu
Website: clasweb.clas.wayne.edu/
asodja
Ph.D., University of California, Davis,
1974
American Cancer Society
Postdoctoral Fellowship and CIT
Fellow in Chemistry, California
Institute of Technology, 1974-78
Joined WSU faculty, 1978
Blood-sucking insects, including
Aedes aegypti, are disease-carrying
agents resulting in millions of deaths
and debilitations per year. The major
sensory system guiding these insects
to a blood meal is the olfactory,
which is still poorly understood.
We are investigating the multigene
family encoding odorant-binding
proteins (OBPs) in A. aegypti that
transmit viruses causing yellow fever,
dengue/dengue hemorrhagic fevers,
human and equine encephalitis,
among others. Thus it is of major
global public health, agricultural and
economic concern.
The first biochemical event in
olfactory signal transduction is
the interaction between airborne
odorant(s) and an OBP. The OBPs
are present in the sensillar fluid
bathing the olfactory neuron, with
the olfactory receptors located
on its dendritic end. Although
much is known about the OBPs
and the genes encoding them,
understanding the exact function(s)
and mechanism(s) by which they
execute them in olfaction is murky at
best. Using in situ hybridization and
qRT-PCR analyses, we determined
the spatial and temporal expression
profile of one of about 70 A. aegypti
OBP genes. Our data revealed
a novel expression pattern of
this OBP, whose transcripts were
detected in olfactory and all other
sensory and several non-sensory
tissues in adults and in pre-adult
stages. It is also expressed in
sexually dimorphic fashion. How
this single gene product functions
in the diverse cellular contexts is
the current pursuit of my research
investigations. The specific function
within a given tissue may be through
the interaction of this OBP with a
molecular partner specific for the
tissue. Our preliminary data suggests
that the interaction of this OBP is
with a non-OBP family member,
within which homo- and heterodimers between different OBPs have
been observed. Our findings to date
suggest that the OBP we are working
with performs additional functions
outside its role in olfaction.
We anticipate that the data
obtained will further our molecular
understanding of OBP functions
and identify molecular targets for
developing genetic or chemical
approaches to decrease and
possibly eliminate the vector
capacity of A. aegypti and other
blood-sucking insects, and thus
decrease transmission of deadly or
debilitating diseases.
S E L E C T E D P U B L I C AT I O N S
Mairiang D., Zhang H., Sodja A.,
Murali T., Suriyaphol P., Malasit
P., Limjindaporn T., Finley R.L., Jr.
2013. Identification of new protein
interactions between dengue fever
virus and its hosts, human and
mosquito. PLoS One 8:e53535.
Sodja A., Palomino E. 2008. OdorantBinding Proteins and Mosquito
Repellents: Lessons Learned. In:
R.P.Maes, editor. Insect Physiology:
New Research. New York: Nova
Science Publishers, Inc. p. 295-306.
24
Palomino E., Sodja A. 2007. Method
and Apparatus for the In-Vitro
Evaluation of Substances as Mosquito
Repellents. Patent # US 7,275,499
B2 (2/10/07).
Sodja A., Fujioka H., Lemos F.J.,
Donnelly-Doman M., Jacobs-Lorena
M. 2007. Induction of actin gene
expression in the mosquito midgut
by blood ingestion correlates with
striking changes of cell shape. J
Insect Physiol 53:833-839.
Sodja A. 2002. Molecular Study
of Olfaction in Aedes aegypti.
Proceedings of the Michigan
Mosquito Control Association 15:
1115-1125.
THE ECOLOGY OF FRESHWATER PLANKTON
I am an aquatic ecologist interested
in the ecological and evolutionary
processes that determine the structure
and stability of populations and
communities. As anthropogenic
threats to species and genetic diversity
continue to increase in scale and
magnitude, a major challenge facing
biologists is predicting the trajectory
of biodiversity loss and its impacts
on the stability and functioning of
ecosystems. Gaining this predictive
capacity depends greatly on
identifying the mechanisms that
maintain patterns of biodiversity, and
understanding how alterations in
biodiversity can impact community
and ecosystem properties under
environmental change. My research
focuses on understanding the causes
and consequences of biological
diversity in freshwater planktonic
populations and communities. I use
a variety of approaches in my work,
including observational studies, direct
experimental manipulations (in both
field and lab) and occasional forays
into mathematical models. A major
component of my research is focused
on the effects of species loss and
variation in community structure on
emergent community and ecosystem
properties such as trophic-level
production and dynamic stability
in variable environments. I also use
experiments to examine the flipside
of this issue: the factors that mediate
the strength and outcome of biotic
interactions, particularly the effects
of spatiotemporal heterogeneity on
interspecific competition, species
coexistence and patterns of diversity.
My more recent research pursuits have
begun to integrate spatial processes
and the role that dispersal plays in
mediating patterns of species diversity,
and the stability of populations and
communities. I have also begun to
utilize molecular tools to explore the
causes and ecological consequences
of intraspecific variation and genetic
diversity of Daphnia pulex populations
(a keystone species in the Pond
Systems I study).
CHRIS STEINER
Associate Professor
Office: 3121 BSB
Phone: 313-577-0728
Email: csteiner@wayne.edu
Website: clasweb.clas.wayne.edu/
csteiner
Ph.D., Zoology, Michigan State
University, 2001
Postdoctoral Research Associate,
University of Chicago, 2001
NSF Postdoctoral Fellow, Rutgers
University, 2002-04
Postdoctoral Research Associate,
University of Illinois, 2004-05
Postdoctoral Research Associate,
Michigan State University, 2005-08
Joined WSU faculty, 2008
S E L E C T E D P U B L I C AT I O N S
Steiner C.F., Stockwell R.D.,
Kalaimani V., Aqel Z. 2013.
Population synchrony and
stability in environmentally forced
metacommunities. Oikos:no-no.
Steiner C.F., Klausmeier C.A.,
Litchman E. 2012. Transient
dynamics and the destabilizing
effects of prey heterogeneity.
Ecology 93:632-644.
Steiner C.F. 2012. Environmental
noise, genetic diversity and the
evolution of evolvability and
robustness in model gene networks.
PLoS One 7:e52204.
Steiner C.F., Stockwell R.D., Kalaimani
V., Aqel Z. 2011. Dispersal promotes
compensatory dynamics and stability
in forced metacommunities. Am Nat
178:159-170.
Steiner C.F., Schwaderer A.S., Huber
V., Klausmeier C.A., Litchman E.
2009. Periodically forced food-chain
dynamics: model predictions and
experimental validation. Ecology
90:3099-3107.
25
SIGNALING DURING AXON PATHWAY FORMATION
MARK VANBERKUM
Professor
Office: 3177 BSB
Phone: 313-577-5554
Email: mvanberk@biology.biosci.
wayne.edu
Website: bio.wayne.edu/profhtml/
vanberkum/VanBerkum.html
Ph.D., Baylor College of Medicine,
1991
Postdoctoral Fellow, Medical
Research Council of Canada,
University of California, Berkeley,
1991-95
Joined WSU faculty, 1995
Directional movement of the growth
cone, the terminal extension of the
outgrowing axon, is a complex signal
transduction process dictated by
a series of attractive and repulsive
guidance cues lining the path. Cell
surface receptors detect these cues
and initiate intracellular signaling
events to dictate axon outgrowth
and steering. We seek to understand
this signaling process by studying
an axon’s decision to cross or not to
cross the midline of an embryo using
the molecular, cellular and genetic
toolbox of Drosophila.
A second project examines the role
of Adhesion G-Protein coupled
receptors (GPCRs) in the formation
of the embryonic nerve cord. GPCRs
are familiar receptors for hormones
and neurotransmitters that activate
trimeric G-proteins. The growing
family of Adhesion GPCRs is thought
to activate G-proteins in response to
adhesive conditions dictated by their
extracellular domains. We are using
the Drosophila genetic toolbox to
begin testing whether these receptors
might play a role in the development
of the nerve cord.
The ventral cord of a Drosophila
embryo is a ladder-like scaffold of
axons with an anterior (AP) and
posterior (PC) commissure joining
longitudinal connectives (LC) on
each side of the midline. Netrins
are chemoattractive cues guiding
axons across the midline. Netrins are
detected by Frazzled, which in turn
activates several intracellular signaling
pathways to regulate axon outgrowth.
One signaling molecule appears to
be Abelson Tyrosine Kinase, a major
regulator of actin dynamics. We are
seeking to understand how Frazzled
and Abelson cooperate to guide axons
across the midline. This project utilizes
biochemical and cellular techniques to
understand how Frazzled and Abelson
physically interact, while genetic
manipulations help us understand
how they work in vivo to establish
axon connections.
S E L E C T E D P U B L I C AT I O N S
Patel M.V., Hallal D.A., Jones J.W.,
Bronner D.N., Zein R., Caravas J.,
Husain Z., Friedrich M., Vanberkum
M.F. 2012. Dramatic expansion
and developmental expression
diversification of the methuselah
gene family during recent Drosophila
evolution. J Exp Zool B Mol Dev Evol
318:368-387.
26
Dorsten J.N., Varughese B.E., Karmo
S., Seeger M.A., VanBerkum M.F.
2010. In the absence of frazzled overexpression of Abelson tyrosine kinase
disrupts commissure formation and
causes axons to leave the embryonic
CNS. PLoS One 5:e9822.
Dorsten J.N., VanBerkum M.F. 2008.
Frazzled cytoplasmic P-motifs are
differentially required for axon
pathway formation in the Drosophila
embryonic CNS. Int J Dev Neurosci
26:753-761.
Hsouna A., VanBerkum M.F. 2008.
Abelson tyrosine kinase and
Calmodulin interact synergistically to
transduce midline guidance cues in
the Drosophila embryonic CNS. Int J
Dev Neurosci 26:345-354.
Dorsten J.N., Kolodziej P.A.,
VanBerkum M.F. 2007. Frazzled
regulation of myosin II activity in the
Drosophila embryonic CNS. Dev Biol
308:120-132.
THE SUMO-MODIFICATION PATHWAY
My laboratory is interested in
understanding the role of the
SUMO-modification pathway in cell
cycle regulation, nucleocytoplasmic
transport and human diseases,
including cancers. Small ubiquitinrelated modifier proteins (SUMOs)
are dynamically conjugated to a wide
variety of proteins and thereby affect
protein activity, localization, stability
and protein-protein interaction. As a
major regulatory mechanism conserved
in eukaryotes, sumoylation regulates
many essential cellular processes,
including cell cycle progression,
nucleocytoplasmic transport, stress
response, gene expression, signal
transduction and genome stability.
Sumoylation is catalyzed by a cascade
of enzymes, including an E1 activating
enzyme (SAE1/2), an E2 conjugating
enzyme (Ubc9), and multiple E3
ligases. As a reversible process of
sumoylation, SUMOs are deconjugated
from their substrates by
SUMO-specific isopeptidases
called SENPs in mammals.
Consistent with its essential
functions, perturbations
of sumoylation have
been implicated to
multiple human diseases,
including cancers and
neurodegenerative diseases.
Among the three human
SUMO paralogs, SUMO-2
and SUMO-3 are about 96
percent identical to each other and
thereby referred to as SUMO-2/3, but
they share less than 50 percent identity
to SUMO-1. Accumulating lines of
evidence have revealed that SUMO-1
and SUMO-2/3 modifications have
overlapping but also distinct functions.
We currently focus on elucidating the
molecular details of how an imbalance
in sumoylation contributes to breast
cancer progression and metastasis;
how SUMO-2/3 modification regulates
CENP-E localization to kinetochores
and chromosome alignment to
metaphase plates; the molecular
mechanisms underlying Ubc9 nuclear
localization in mammalian cells; how
and why RanGAP1 shuttles between
the nucleus and the cytoplasm; and the
roles of SUMO-1-modified RanGAP1
at the pore complexes of annulate
lamellae, a cytoplasmic organelle with
largely unknown function.
XIANG-DONG ZHANG
Assistant Professor
Office: 4115 BSB
Phone: 313-577-0606
313-577-6891
Email: xiang-dong@biology.biosci.
wayne.edu
Website: clasweb.clas.wayne.edu/
xiang-dong
Ph.D., Molecular Biology, Mississippi
State University, 2002
Postdoctoral Fellow, Johns Hopkins
University, 2002-09
Joined WSU faculty, 2009
S E L E C T E D P U B L I C AT I O N S
Wan J., Subramonian D., Zhang X.D.
2012. SUMOylation in control of
accurate chromosome segregation
during mitosis. Curr Protein Pept Sci
13:467-481.
Zhang X-D., Matunis M.J. 2009.
Chromosome movement via multiple
motors: novel relationships between
KIF18A and CENP-E revealed. Cell
Cycle 8:3257-3258.
Jeram S.M., Srikumar T., Zhang X.D.,
Anne Eisenhauer H., Rogers R.,
Pedrioli P.G., Matunis M., Raught B.
2010. An improved SUMmOn-based
methodology for the identification of
ubiquitin and ubiquitin-like protein
conjugation sites identifies novel
ubiquitin-like protein chain linkages.
PROTEOMICS 10:254-265.
Zhu S., Goeres J., Sixt K.M., Bekes
M., Zhang X.D., Salvesen G.S.,
Matunis M.J. 2009. Protection
from isopeptidase-mediated
deconjugation regulates paralogselective sumoylation of RanGAP1.
Mol Cell 33:570-580.
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29
DEGREE PROGRAMS
D O C TO R O F P H I LO S O P H Y ( P H . D.)
clasweb.clas.wayne.edu/biology/phdprogram
The Ph.D. curriculum produces scholars and independent researchers.
Students complete a rigorous curriculum that includes core courses and
electives. Admission is to the Ph.D. program rather than an individual
lab. Laboratory rotations during the first year provide the knowledge and
experience necessary to select a host lab. Several years of intensive research
culminate in writing and defending the Ph.D. dissertation. Recent graduates
of the Wayne State University Ph.D. program in biology have accepted
positions in government and industry. They are also postdoctoral researchers
and faculty members at top colleges and universities.
M A S T E R O F S C I E N C E I N B I O LO GY ( M . S . B I O LO GY )
clasweb.clas.wayne.edu/biology/msprogram
The M.S. in biology includes an intensive curriculum of core and elected
courses. Two laboratory rotations during the first semester culminate in
selection of a host lab and completion of a thesis project. Research undertaken
for an M.S. in biology is less extensive than that necessary for a Ph.D., enabling
completion of an M.S. in approximately three years. An M.S. in biology is a
qualification for many positions in industry, research and education. The M.S.
in biology also is excellent preparation for advanced graduate programs.
M A S T E R O F S C I E N C E I N M O L E C U L A R B I OT E C H N O LO GY
( M . S . B I OT E C H )
clasweb.clas.wayne.edu/biology/msbiotechprogram
The M.S. Biotech is a two-year program. The first nine months are devoted to
coursework, and the remainder of the program involves a full-time laboratory
project and an internship. This program is designed to give students the skills
required for a career in biotechnology.
M A S T E R O F A R T S I N B I O LO GY ( M . A .)
clasweb.clas.wayne.edu/biology/maprogram
The M.A. provides a solid foundation in biological theory to supplement
careers in business, law, education or public health. Some students choose an
M.A. in biology when contemplating a career change. The M.A. in biology
also can be a springboard to medical school or an advanced graduate
program. Fulfillment of the course requirements for an M.A. in biology can be
accomplished in two years, but this plan of study is also appropriate for those
who need a flexible course load to balance family or work.
30
LABORATORIES AND FACILITIES
The seven-story Biological Sciences
Building is located at the south end
of Wayne State University’s main
campus and contains 31 research
laboratories, totaling 30,648 square
feet. Seminar rooms, conference
rooms and classrooms are located
within the building, and informal
meeting areas are found on each
floor. Common facilities include
darkrooms, cold rooms, rooftop
greenhouses, glassware washing and
autoclave facilities. The biological
imaging facility houses a Leica TCS
SP2 spectral photometer laserscanning confocal microscope for
digital, high-resolution imaging
of fluorescently labeled cells and
tissues. Additional shared equipment
includes refrigerated, high-speed and
ultracentrifuges; scintillation counters;
UV-Vis spectrophotometers; real-time,
quantitative PCR cycling machines;
a Typhoon imaging system; UV
and white light image processor
and documenter; and an X-ray film
developer. The basement houses
mouse, rat and Drosophila breeding
and maintenance facilities.
These departmental facilities are
complemented by newly renovated
space in the Wayne State University
School of Medicine, which offers
core facilities that support molecular
and genomic research. This includes
services such as study design, nucleic
acid isolation, genotyping, expression
analysis and sequencing with major
equipment like the Affymetrix
microarray systems and the Illumina
HiSeq 2500 platforms.
The College of Liberal Arts and
Sciences maintains several facilities
that support our research programs.
The science storeroom stocks an
extensive inventory of chemicals,
laboratory consumables, small
equipment items, biochemical
and molecular biological reagents,
and related supplies for rapid onsite purchase. The electronics and
computer shop provides services for
the design and repair of electronic
equipment as well as diagnosis and
repair of malfunctioning computers.
The college also supports a central
instrumentation facility, which houses
mass spectrometers, rapid-scanning
and CD/ORD spectrophotometers,
X-ray crystallography and
electron paramagnetic resonance
instrumentation. In addition,
biological nuclear magnetic
resonance experiments can be
carried out using 300, 400 and 500
MHz spectrometers.
31
ADMISSIONS
The Department of Biological Sciences takes a holistic approach to admission
into the graduate program. We recognize that motivation, vision and
evidence of creative potential are the best indicators of a successful student
and scientist. A minimum requirement is the completion of a bachelor’s or
its equivalent in biology or a related field from an accredited university, with
coursework in the area of intended specialty.
Applications must be submitted online and can be accessed at clasweb.clas.
wayne.edu/biology/gradonlineapplication. To ensure a review of your
application to the Ph.D. program and consideration for full financial support,
applications must be submitted by December 1. Decisions will be made on
a continuous basis and later applications may not be reviewed if all open
positions are filled. The final university-mandated deadlines for applications
are March 1 for international applicants and April 1 for domestic applicants.
A completed application for admission to the graduate program must include
the following:
n A
pplication forms
n O
fficial transcripts for all undergraduate and graduate institutions attended
(foreign transcripts must have an official translation)
n O
fficial results of the general tests of the Graduate Records Examinations
(GRE) sent directly from the Educational Testing Service
n T
hree letters of recommendation
n A
personal statement that addresses the questions posed in the application
instructions
n International students only: Official results of the TOEFL Examination —
A minimum acceptable TOEFL score is 79/80 on the Internet-based form,
213 on the CBT or 550 on the paper-based form
32
FINANCIAL SUPPORT
All students accepted into the Ph.D. program are admitted with an offer of
financial support, which includes a stipend and benefits described below. The
Department of Biological Sciences, through the College of Liberal Arts and
Sciences and the Graduate School, offers several kinds of support. Graduate
teaching assistantships are the primary source. Graduate teaching assistants
teach many of the undergraduate and graduate laboratory sections.
Additional forms of support granted on a competitive basis include the following:
n T.C. Rumble university graduate fellowships
n Graduate Research Assistantships
n Vice President for Research graduate assistantship
n Provost Enhancement graduate research assistantships
The assistantships and fellowships include a tuition scholarship covering the
costs of tuition, paid medical and dental insurance for the student, and a
subsidy for family coverage if appropriate. Supplemental summer support is
also available.
33
B I O LO G I C A L S C I E N C E S
1360 Bio Science Bldg
Detroit, MI 48202
Phone: 313-993-4217
Fax: 313-577-6891
Website: clasweb.clas.wayne.edu/biology
Email: ac0485@wayne.edu
Wayne State University Board of Governors
Debbie Dingell, chair, Gary S. Pollard, vice chair, Eugene Driker,
Diane L. Dunaskiss, Paul E. Massaron, David A. Nicholson,
Sandra Hughes O’Brien, Kim Trent, M. Roy Wilson, ex officio
34