2015 Biomedical Sciences Summer Projects
Dr. Luiz Bermudez
1. Mycobacterium paratuberculosis. How the bacterium trick the immune system to cause and
block inflammation.
2. Hospital infection: Emergency of resistance to methicillin in Staphylococcus
pseudointermedius.
Dr. Rob Bildfell
rob.bildfell@oregonstate.edu
Echinococcus in Oregon canids. This project was funded last year but the student, Kathyrn Gaub,
elected to take a Merck-Meriel research opportunity in India instead. I believe that Ms Gaub
hopes to apply for this project again. The project is a survey for E. granulosus in intestinal tracks
of coyotes and foxes in Oregon. To our knowledge such a survey has not been performed and
there is a possibility that prevalence of this zoonotic pathogen may change as wolves become
more abundant on the Oregon landscape. The survey will be performed with the cooperation of
the Oregon Department of Fish and Wildlife, who have already acquired some intestinal tracts
for analysis.
EHD serology at Wildlife Safari wit Dr. Alcantar. Last year was the first documented incursion
of EHD into the park, resulting in the death of several yak and one elk. Assuming the Culicoides
vector has relatively equal access to most ungulates in the park, this represents a rare opportunity
to see which species were exposed and failed to develop clinical disease. Archived serum
samples are also available to determine whether there have been previously undetected
incursions. Student will participate in collection and analysis of serum samples.
Coccidiodiomycosis. Oregon Department of Public Health is concerned about the possibility of
this fungal disease in Eastern Oregon. The OSU VDL has a serologic test for the agent but
acquiring suitable samples for testing is problematic. This project would require the student
forming linkages with Wildlife Services Division of APHIS and other sources in
eastern/southern Oregon to perform a serosurvey.
Dr. Patrick E. Chappell
patrick.chappell@oregonstate.edu
(541) 737-5361
The Chappell lab explores three major research directions, all centered on the role of the
molecular circadian clock in normal reproductive function, as well as in the etiology and
progression of hormone-dependent cancers.
1) We are investigating the role of endogenous intracellular circadian clocks in the
neuroendocrine regulation of reproduction in mammals. Using a combination of molecular
biological and physiological techniques, we are exploring how oscillatory gene expression
patterns in hypothalamic gonadotropin-releasing hormone (GnRH) and kisspeptin (Kiss-1)
neurons modulate secretion of these neuropeptides, which are crucial for pubertal progression,
gamete and steroid hormone production, and ovulation in females. We utilize several models of
molecular circadian clock disruption, and are determining the necessity of cell-specific clocks
using multiple transgenic mouse lines. Additionally, we have created several sub-cloned
immortalized cultured neuronal cell lines, in which we can monitor clock oscillations
concomitantly with peptide secretion, and in which we can reversibly disrupt clock function.
Specific projects available include examining the effects of estrogen feedback on GnRH
neuronal gene expression patterns, activity, and secretion, using both in vitro cell culture and in
vivo mouse models, and investigating the role of clock gene expression patterns in the initiation
and progression of reproductive cancers, particularly mammary cancer. Students will use
methodologies ranging from real-time quantitative RT-PCR, transient transfection of cultured
cells, evaluation of reproductive capacity in mice, and monitoring gene expression and protein
abundance changes in cells using fluorescence microscopy and luminometry.
Summer students will have the opportunity to perform studies which provide insight into broad
mechanisms of endocrine neurosecretion, and advance circadian biology by exploring how
transcriptional oscillations can control synchronous multi-cellular events to regulate numerous
biological processes and even orchestrate complex behaviors. Potential applications of this
research include new directions in treating a range of reproductive physiological disorders that
result from malfunction of hypothalamic neurosecretion, including polycystic ovarian syndrome
(PCOS) and primary ideopathic hypogonadism, both of which are associated with atypical
hormone release patterns.
2) In collaboration with Dr. Shay Bracha in the Clinical Sciences department, we have begun
funded projects investigating the role of cell-specific oscillators in the etiology and progression
of mammary cancer cells in dogs, and students could be involved in performing several of the
above methodologies to monitor gene expression patterns in cancer cell lines, as well as
performing a host of assays evaluating cell proliferation, differentiation, and programmed cell
death. Another collaborative project examines the role of autocrine production of GnRH and
Kiss-1 by osteosarcomas using both primary canine tumor tissue and cell lines, and how these
unusual expression and secretion patterns modulate proliferative rate of these cancers.
3) A third project in my laboratory involves both local and international collaborators to explore
reproduction in scleractinian coral, using available cnidarian genome databases to investigate
how coral, anemone, and hydra use hormonal signals to time gamete maturation and release.
Students involved in this project would learn protocols in genomic data mining, hormone binding
assays, and immunohistochemistry.
Dr. Jean Hall
Jean.Hall@oregonstate.edu
Dryden 206, 7-6537
My project involves cows supplemented with selenium and its effects on immune responses,
animal health, and animal production. In particular, we are interested in using selenium as a
fertilizer to enrich forages fed to ruminants. There will be opportunities this summer to help
develop assays to assess immune function in cattle as a response to consumption of Se-fertilized
forage.
Dr.Ling Jin & Tim Miller-Morgan
ling.jin@oregonstate.edu
1) Development of treatment that can control KHV latent infection.
Cyprinid herpesvirus 3, or koi herpesvirus (KHV), is a deadly virus that affects koi and carp
worldwide. It causes severe gill necrosis and nephritis, dermal ulceration , hemorrhage, and
mass mortality of up to 100% of affected fish. Fish that survive KHV infection are latently
infected lifelong carriers. Little is known about the molecular mechanisms and control of
latency of KHV. Our previous work has demonstrated that in KHV-infected koi, the virus
becomes latent in leukocytes, specifically in circulating IgM+ B cells. Similar to many
mammalian herpesviruses, a latency-associated viral gene, ORF6, was also identified in KHVinfected B cells. Our recent work demonstrated that ORF6 protein is made during latent
infection and may be sumoylated during productive infection. In this research project, we
hypothesize that ORF6 protein is required for maintaining the latent infection, and blocking
ORF6 protein expression will result in termination of KHV latency. To test our hypothesis, we
plan to treat koi with PMO which can block the ORF6 protein synthesis. To determine whether
ORF6 is required for latency maintenance, ORF 6 expression will be blocked during latency by
anti-sense technology with vivo-morpholino (PMO). KHV latency will be compared between
PMO treated and un-treated groups of koi. Through this aim we will know if ORF6 can serve as
treatment target to eliminate latent infection.
2) Investigation of ORF6 protein post-translational modification during KHV latency
Cyprinid herpesvirus 3, or koi herpesvirus (KHV), is a deadly virus that affects koi and carp
worldwide. It causes severe gill necrosis and nephritis, dermal ulceration , hemorrhage, and
mass mortality of up to 100% of affected fish. Fish that survive KHV infection are latently
infected lifelong carriers. Little is known about the molecular mechanisms and control of
latency of KHV. Our previous work has demonstrated that in KHV-infected koi, the virus
becomes latent in leukocytes, specifically in circulating IgM+ B cells. Similar to many
mammalian herpesviruses, a latency-associated viral gene, ORF6, was also identified in KHVinfected B cells. Our recent work demonstrated that ORF6 protein is made during latent
infection. The ORF6 protein detected in productive infection appear to have a molecular mass of
~140 kDa; which is greater than its predicted molecular mass of 81.5 kDa. When ORF6 amino
acid sequence was queried with the sumoylation site prediction software GPS-SUMO, 5
potential sumoylation sites were identified. With an added mass of five 11.5 kDa proteins it
would explain the augmented shift from predicted molecular mass observed for ORF6 protein in
infected CCB cells. In this summer research porject, ORF6 protein post-translational
modification will be invested by antibody specific for sumoylation or phosphorylation.
Dr. Deidre Johns
Deidre.johns@oregonstate.edu
Medicinal chemistry/synthetic organic chemistry: We design and synthesize small molecules to
advance the study of disease targets and develop small molecule therapeutics. Our small
molecules help to understand protein binding pockets by probing specific interactions and its
effect on activity and binding affinity. We synthesize the small molecule probes using modern
multi-step organic synthetic methods. Our collaborators evaluate the compounds against
particular therapeutic targets. We use the data to further refine our compound designs and
prepare the next generation of small molecules. Two projects are currently available: (1) design
and synthesis of antibiotics with a new mechanism of action. In collaboration with Dr. Sikora,
Pharmaceutical Sciences, we are preparing compounds to inhibit AniA, an enzyme involved in
gonorrhea survival and biofilm formation. We design AniA inhibitors using the protein crystal
structure of AniA. The compounds we prepare will be evaluated for inhibition of enzymatic
activity and binding affinity in the Sikora lab. (2) design and synthesis of a fragment compound
library. This project enables a significant amount of creative freedom to design and prepare
fragment compounds. The library will be used to identify modulators for a variety of therapeutic
targets in the future.
Dr. Anna Jolles
jollesa@science.oregonstate.edu
1. Risk sensitive foraging in African buffalo.
This project examines how wild African buffalo balance parasite exposure risk versus nutrient
intake in their foraging decisions. The study is based at Kruger National Park, South Africa, and
uses observational and experimental approaches to evaluate to what extent avoiding parasites
(ticks and GI helminths) drives habitat utilization patterns by buffalo. This work extends the
concept of the “landscape of fear”, which posits that wild herbivores must balance predation risk
versus nutrient intake, to include parasites as natural enemies that might be just as relevant to
foraging behavior as predators. The project is led by a PhD student under Dr. Jolles’
supervision. There is scope for a veterinary student to contribute to the project by defining a
portion of the project that s/he can be responsible for, according to her interests, and conducting
the field and lab work needed to complete it. This will involve long days in the field and lab, and
will require working well as part of a close-knit research team, as well as independently.
2. Linking animal personality with immunity and pathogen exposure patterns.
The term “animal personality” refers to the finding in behavioral studies that there is strong
variation among individual animals in their behavioral responses, and that this variation is
consistent across a range of situations. I.e., individuals can be classified as bold vs shy, or
inquisitive vs not, or leader vs follower, etc, and respond to new situations in predictable ways
according to their personality. The question investigated here is to what extent personality traits
in buffalo are associated with variation in immunity and infections. For example, inquisitive
animals may tend to encounter more pathogen / parasite exposures than less curious animals, due
to increased exploratory behaviors, -- and this may underlie some of the variation in immunity
that we observe among buffalo. This project is led by a PhD student under Dr. Jolles’
supervision, and is based in Kruger National Park, South Africa. In summer 2015 we will use a
series of behavioral field experiments to classify buffalo personalities, which we can then
correlate to immunological and infection data that we are collecting on the same animals. A
veterinary student could contribute to this project by focusing on particular personality, immune
or infection traits (according to her / his interests), carving out a research project of manageable
scope. This will involve long days in the field and lab, and will require working well as part of a
close-knit research team, as well as independently.
Dr. Mike Kent
Michael.kent@oregonstate.edu
1) Investigation of the cause of mortality in endangered suckers in Klamath Lake.
Dr. Kent’s research focuses on diseases and parasites of fishes. For summer 2015, we have a
project available working on diseases and pathogens in shortnose and Lost River suckers in
Klamath Lake. Certain species of suckers in this lake are listed as endangered, and our initial
surveys have revealed massive infections by the metacercariae of several trematode species and
an aniksine nematode in the heart. Our overall project has two aims: 1) Determine which
parasites, and to what extent, they impact survival of suckers, and 2) Elucidate the life cycles of
these parasites. For Aim 1, we will use well-accepted methods to determine the extent of
parasite associated mortality. These include 1) Thorough necropsies, 2) Determining the
frequency of lethal infections, 3) Observing differential mortality from a decrease in frequency
of long-lived parasites with host age; etc.
For Aim 2 (life cycles), we propose to will continue our life cycle studies using molecular and
morphological endpoints of the parasite fauna of Upper Klamath Lake. For the typical trematode
life cycle, that includes a snail or limpet first intermediate host, fish as second intermediate host
and a fish–eating bird as the final host. Our strategy is to identify parasites in Upper Klamath
Lake suckers using morphological and molecular techniques, then survey cercariae in molluscs
and adult trematodes in guts of birds and mammals to find a match to the sucker parasite.
The candidate will have the opportunity to work on one or both of these aims. Tasks during the
summer will include assisting the Kent lab staff and graduate students with collecting fish and
snails at Klamath Lake, conducting necropsies, identification of parasites in wet samples, and
recording histological changes. For Aim 2, the candidate would maintain live snails collected in
the field, harvested cercariae shed by snails, record morphologic features, and preserve for
molecular identifications. We may also have birds available for collecting adult worms. I
envision that the candidate would participate and assist with various activities outlined above,
and select one small project that they would take the lead on.
Dr. med. vet. Christiane Löhr, PhD, DACVP
Christiane.Loehr@oregonstate.edu M144
I work as diagnostic pathology in the Veterinary Diagnostic Laboratory. I am intrigued by the
cellular and molecular mechanisms leading to diseases particularly when examined in the context
of tissues and whole organisms. I have a particular interest in dermatopathology, camelid and
goat diseases, forensics, and the pathogenesis and prevention of neoplastic conditions (cancer). I
have three specific projects, but am open to other research ideas within the areas of diagnostic
pathology and cancer biology. Projects usually span from design to manuscript draft preparation
including review of clinical records, analysis of pathology reports, and often slides analysis, and
may include analysis of immunohistochemical staining characteristics, tissue microarray
assembly, and application of molecular techniques.
Canine Acanthomatous Ameloblastoma - Cancer Biology and Diagnosis
Tumors of the gingiva and jaw are a frequent occurrence in small animals. One of the most
common oral tumors in dogs is canine acanthomatous ameloblastoma, which is thought to
originate from epithelial cell nests left over after completion of tooth development (i.e.,
odontogenic epithelium). Acanthomatous ameloblastoma (CAA) can be confused clinically and
histologically with oral squamous cell carcinoma (SCC). Both tumors grow locally infiltrative.
However, CAA does not metastasize and thus carries a much better prognosis than SCC. This
project examine the phenotypic and mechanistic differences between CAA and SCC to aid
diagnostics and elucidate biologically relevant differences.
Feline injection site sarcoma – Molecular mechanisms
Injection site associated sarcomas in cats are highly aggressive malignancies. Feline injection
site sarcoma (FISS) deeply and unpredictably infiltrate surrounding tissues frequently resulting
in recurrene after surgical treatment. microRNAs are small non-coding RNAs that contribute to
regulation of cell function. This project will examine microRNA species identified by sequence.
Enhancing Diagnostics and Research through Digital Image Analysis
The microscopic evaluation of tissues is accurate and reliable at identifying specific disease
processes and establishing accurate diagnoses. In an experimental setting, ‘manual’ analysis of
individual slides is very time consuming and can be extremely tedious especially when aimed at
quantitation. This project will establish protocols to analysis slides from a project using open
source software.
Dr. Jan Medlock
jan.medlock@oregonstate.edu
Pet health insurance gives us one way to look at how people value their pets. The difference
between the amount paid in as premiums and the amount paid out as claims, estimated from data
from insurance companies and our patient records, gives an estimate of how owners value their
pets and risks to their pets' health. Such values are essential to evaluating the effectiveness of
interventions to improve pet health.
Dr. Hong Moulton
hong.moulton@oregonstate.edu
Morpholino oligomers are a class of antisense molecules that have been widely used to knock
down gene expression, modify pre-mRNA splicing or inhibit miRNA maturation and
activity. Morpholino oligomers have revolutionary potential for treatment of a broad range of
human diseases, including viral, bacterial, age-related and genetic diseases, but they suffer from
poor delivery into cells. My long term research interest has been in inventing and improving
methods for enhancing the delivery of Morpholinos in a tissue-specific manner for genetic
diseases (such as Duchenne Muscular Dystrophy) and infectious diseases. I am looking for
motivated students with an interest in those research areas. Students will be trained in planning
experiments, biochemistry and molecular biology lab technologies, collect and analyze data for
publications. A commitment of a full summer is expected and continued involvement in
preparation of the projects into a manuscripts.
The goal of the project is to identify a delivery method or a chemical identity which has
characteristics superior to the current state of art. We will use mammalian cell culture systems
and/or a zebrafish model to target specific mRNAs with Morpholino oligos. Cellular delivery
efficacy and toxicity of the compounds will be evaluated primarily by RTPCR, immunoblotting,
fluorescence-microscopy and cell viability assays.
Dr. Kathy O’Reilly
koreilly@oregonstate.edu
Gastric infections by Haemochus contortus (Trichostrongylida) can be very pathogenic to
ruminants, causing severe anemia. We have developed a sensitive and relatively inexpensive
diagnostic test to differentiate eggs of this nematode from those of other trichostrongyles that
infect ruminants. This test is a lectin-based test which allows for reliable differentiation between
H. controtus and other trichostrongyle ovas. The objective this study is to use this test to evaluate
the prevalence and distribution of H. contortus in the bovine populations in Oregon and
Washington. While Haemonchus contortous has been found in cattle in Oregon, it has typically
been in the warmer, drier geographical areas of the state. There are preliminary results
demonstrating that it is moving into the Western area of the state. This study would be a survey
to evaluate if this pathogenic parasite is moving into these other areas.
Dr. Stephen Ramsey
Stephen.ramsey@oregonstate.edu
Transcriptome profiling study of immune cells during plaque regression
The pathological condition underlying the majority of cardiovascular disease cases (which
collectively account for one in four deaths in the United States) is atherosclerosis, an
inflammatory disease in which arteries develop lipid-rich atheromatous plaques that can
ultimately rupture and cause an infarction (1). In inbred laboratory mouse models of
atherosclerosis, plaque can be induced to regress through genetic recombination-induced lipid
lowering (2) as well as through administration of lipid-lowering biologics (3). In mouse, lipid
lowering in vivo appears to trigger the emigration of macrophages (key cells of the innate
immune system) from the plaque (4) and concomitant broad changes in the macrophage
transcriptome (5,6). Despite intense interest in the macrophage as a potential cellular target for
prevention or treatment of atherosclerosis (7), the gene regulatory interactions that connect
changing lipid levels to macrophage directional motility are poorly understood, and this has
limited the yield of new macrophage-specific molecular targets in pathways activated by
lipoproteins. A key challenge to studying gene regulation in the context of plaque regression is
that plaque comprises many different cell types, each with a distinct gene regulatory program.
Together with collaborators at NYU, we are using flow cytometry to isolate specific cell
populations (macrophages and T cells) from collagenase-digested mouse plaques. We have
carried out a pilot transcriptome profiling study (using RNA-seq) of plaque-derived macrophages
and T cells from baseline plaques and from plaques undergoing regression. For this summer
project, a trainee will analyze the RNA-seq data to identify macrophage-specific and T cellspecific genes that are differentially expressed during lipid lowering-induced plaque regression.
The project is an excellent opportunity for a student who is already proficient with basic
scripting to learn some more advanced bioinformatics techniques.
Dr. Dan Rockey
rockeyd@oregonstate.edu
We have a couple of opportunities that a CVM student could participate in. First, we are actively
examining mechanisms used by different chlamydiae to recombine. Although the chlamydiae
are resistant to introduction of DNA from other species, they are very adept at recombining
within a species. We have worked on this in the human pathogens, but we now wish to examine
chlamydial recombination in the veterinary pathogens. Specifically, we will examine whether or
not we can show recombination within the species Chlamydia abortus, a significant pathogen of
sheep and goats. It is possible that recombination in this species might lead to antigenic
variation that renders strains more resistant to the protective effects of the commercial vaccine.
A student pursuing this project would conduct laboratory-based culture of C. abortus, and use an
antibiotic selection process to identify recombinants. Progeny recombinants would be cultured
and genome sequenced, and the nature of the recombination explored.
A second project involves examination of genome sequences of chlamydiae cultured from C.
abortus-vaccinate sheep that had still suffered an abortion episode. With this project we are
examining the means that the vaccine might fail in sheep clocks. We will compare the genome
sequence of a strain identified from an aborted sheep with the genome of the vaccine strain,
which we already have. We will ask if there are possible antigenic differences in the strain that
caused the abortion, versus the strain used for vaccination. This information would then be used
to create a next-generation vaccine that might have higher efficacy.
Dr. Mahfuz Sarker
Department of Biomedical Sciences,
216 Dryden Hall,
Tel: 541-737-6918,
E-mail: sarkerm@oregonstate.edu
The gram-positive, spore-forming, anaerobic Clostridium perfringens causes a spectrum of
diseases that remain important medical and veterinary concerns. The most notable of those C.
perfringens diseases are (i) histotoxic infections such as clostridial myonecrosis (also known as
traumatic gas gangrene), and (ii) diseases such as enteritis or enterotoxemias that originate in
the gastrointestinal (GI) tract. C. perfringens spores can play an important role in transmission
of all these diseases. C. perfringens spores can remain in dormancy for extended periods of
time and when nutrients (termed germinants) are available they can germinate and return to life.
Spore germination is also important for C. perfringens disease transmission. For example, from
a practical food safety perspective, the process of germination is of considerable interest
because, (i) germination of C. perfringens spores in foodstuffs can lead to food poisoning; and
(ii) upon germination, these spores lose their resistance and become susceptible to mild
treatments. Therefore, understanding the molecular mechanism of C. perfringens spore
germination might allow modulation of the germination process in foods by identifying either
inhibitors or artificial germinants that could allow the control of spore contamination loads with
milder treatment conditions.
Spore germination is also important for transmission of other diseases, such as spore
germination in wounds can lead to clostridial myonecrosis. Furthermore, germination of C.
perfringens spores in the intestine is presumably important during C. perfringens-associated
non-food-borne human and animal GI diseases, since these illnesses are thought to be
transmitted by ingestion of spores from environmental. Although we have made significant
progresses on mechanism of germination of spores of C. perfringens food poisoning isolates,
nothing is known about the germination of spores of C. perfringens isolates associated with
nonfood-borne human and animal GI diseases. Our long-term goal is to define the mechanism of
germination of spores of C. perfringens isolates associated with animal GI diseases. Summer
student will be involved in (i) identifying specific germinants for spores of C. perfringens animal
isolates; (ii) optimizing the germination conditions for spores of animals isolates; and (iii)
identifying the germination genes in animal isolates using bioinformatic analyses. This pilot
study will help to determine whether the spore germination process
Dr. Natalia Shulzhenko
Natalia.shulzhenko@oregonstate.edu
Trillions of microbes (collectively called microbiota) inhabit our bodies living in a symbiotic
relationship with each other, and with our own cells. Using state-of-the-art sequencing and
bioinformatics methods, we are discovering how important these bugs are in many aspects of our
health and in diseases. The student will participate in a project studying interactions between
microbiota, immune system and glucose metabolism in healthy animals and in a mouse model of
type 2 diabetes. The work will involve assessment of glucose metabolism in live animals,
analysis of microbial composition by DNA sequencing, evaluation of gene expression in mouse
tissues and cell lines as well as other techniques used in the lab.