InTouch
with research
at Stanley Manne Children’s Research Institute
A Formidable Force in Pediatric
Anesthesiology
Fall 2014
Volume 11: Issue 3
The Department of Anesthesiology at Ann & Robert H.
photo: Lurie Children’s Audiovisual Department
A Member of the
McGaw Medical Center
of Northwestern University
Chicago, Illinois
ManneResearchInstitute.org
Lurie Children’s Hospital of Chicago has much about
which to be proud. From a national perspective, its
work in regional anesthesia and pain medicine serves
as a benchmark for institutions around the United
States regarding safety and efficacy. Anesthesiology
attending physicians are heavily involved in training,
techniques and teaching newer modalities. In fact, the
department sets the standard for training programs,
and therefore is highly competitive.
Fellows and young attending physicians
Look for highlighted
text throughout this
issue to link to more
information.
receive some of the best clinical training, have the
opportunity to do research in their areas of interest,
and run workshops and meetings nationally,
allowing them to showcase their talents. In general,
the department is a formidable force in pediatric
Santhanam Suresh, MD
anesthesiology. It is matriculating well-rounded
fellows who are becoming good clinical doctors,
researchers and teachers. These graduates convey that enthusiasm to the next round of trainees.
3
Saving the Sumatran
Rhino
4
Publications
5
Promotions, Tenure
and Honors
6
Events News
7
In the News
8
tool reduces perioperative anxiety, emergence delirium, and time-to-discharge and increases
Trainee News
9
parental satisfaction when compared to midazolam in pediatric patients undergoing
In This Issue
Director’s Message
Katz Summer Scholars 10
2014 Summer Students 11
The department is engaged in three main areas of research:
•
Airway work. Narasimhan (Sim) Jagannathan, MD continues productive collaborations with
manufacturers to refine supraglottic airway devices used in infants and children undergoing
medical procedures and surgery under anesthesia;
•
Regional anesthesia and pain medicine, in which department chair Santhanam Suresh, MD is
considered a national and international expert; and
•
Allaying anxiety. Sam Seiden, MD recently found that a tablet-based interactive distraction
ambulatory surgery.
Says Suresh, “Our focus is clinical research, particularly trying to validate if a new device or drug is
better and safer. In addition, we concentrate on technology, including ultrasonography, to implement
[continued]
Pediatric Anesthesiology (continued)
newer approaches to managing pain.” He feels that research needs to lead to change in practice, and the work
the department has done is an example of this principle. Many pediatric anesthesia guidelines, both nationally
and internationally, come from the department.
The department’s involvement of young physicians in clinical research is resulting in energetic research
teams. In addition, every pediatric anesthesia fellow is required to conduct a research project. Each fellow
is paired with a mentor based on his/her strengths, with the mentor advising the fellow on daily activities,
including research. Because the fellows are motivated to work on projects that they like, this requirement is
quite successful. 78 percent who graduate from the program go on to positions in academic medicine, and
many become thought leaders in top children’s hospitals.
The department has transformed the field of anesthesia by being a showcase for innovation, safety and
education. Suresh is proud of the team effort. “Everybody is given opportunities to participate in the national
meeting of the American Society of Anesthesiologists. The next one in New Orleans in October 2014 will
feature three innovative pediatric anesthesia workshops, all of which are moderated by members of the
department. Considering the talks, panels and scientific presentations, about 30 percent of the meeting’s
pediatric sessions have one of our staff participating in them. This demonstrates their academic and scientific
productivity,” he says.
InTouch
w
ith research
at Stanley Manne Children’s Research Institute
Published by Stanley Manne Children’s
Research Institute
Fall 2014
Volume 11: Issue 3
ManneResearchInstitute.org
Stanley Manne Children’s Research
Institute is the research arm of
Ann & Robert H. Lurie Children’s
Hospital of Chicago, and a virtual
center for pediatric research at
Northwestern University Feinberg
School of Medicine. Founded in
1989, the research enterprise has
grown to include more than 200
investigators and nearly $37
million in external funding for
research, two-thirds from the NIH
and other federal agencies.
He continues, “The department’s influence is a testimony to the incredible staff here. All of our staff
anesthesiologists are willing to support research. People in our department have very inquisitive minds.”
The department has formed a center for excellence to promote education and advancement for regional
anesthesia in children. As the center grows, the team will start looking into more basic mechanisms to advance
pain medicine in children and safely secure airways.
Future areas of research that Suresh is interested in pursuing include healthcare disparities, tracking people
with chronic pain, and newer modalities for educational models to increase awareness of pain mechanisms.
The department has invested in facilities for research, and is pursuing innovative ways to conduct research.
“Everything we do is aimed at reducing exposure and making anesthesia safer for children. We will
continue to pursue this goal in the clinical setting, and in our research,” he concludes.
Santhanam Suresh, MD is
Arthur C. King Professor in
Anesthesiology and Professor
of Anesthesiology and
Pediatrics at Northwestern
University Feinberg School of
Please send questions and
comments to Peggy Murphy:
pemurphy@luriechildrens.org
773.755.7485
225 E. Chicago Ave., M/C 205
Chicago, Illinois 60611
Medicine.
Narasimhan (Sim)
Jagannathan, MD
holding two of the
airway devices he tests
for use in infants and
children
photo: Jan Terry
[Page 2]
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Director’s Message:
Mary J.C. Hendrix, PhD, Children’s
Research Fund Professor, William
G. Swartchild, Jr. Distinguished
Research Professor, President &
Scientific Director, Stanley Manne
Children’s Research Institute
This fall Stanley Manne Children’s Research Institute
welcomed undergraduate post baccalaureates Elizabeth
Morris and Grace Chandler as our inaugural Research Science
Fellows. This issue’s Director’s Message is dedicated to the aspirations of these two research investigators.
Elizabeth “Lizzie” Morris began interning in the laboratory of Jhumku Kohtz, PhD this July to explore
opportunities that would help her determine whether to pursue a career in medicine or biomedical
research. Lizzie graduated with a Bachelor of Arts degree in Neuroscience from Middlebury College in
May 2014, and in discussing her future career goals and inspiration said: “I’m planning on going on to
either medical school or graduate school. As graduation approached, I wasn’t sure which direction to take
and was advised to spend some time working in a lab to gain first-hand experience. This fall I’m taking
some classes and continuing my work in the lab in order to decide which course is best for me. Medicine
provides the opportunity to directly impact patients’ lives, and I am very interested in pediatrics. On the
other hand, research allows me to contribute to and learn from our rapidly expanding knowledge of
biology, which is also appealing. If I choose graduate school I will study something related to molecular
biology and neuroscience.” Lizzie’s project in the Kohtz laboratory consists of addressing long non-coding
Lizzie Morris
RNA-dependent GABAergic interneuron development. As developmental epigenetic events controlling
neural circuits and behavior are poorly understood, she is using quantitative real time PCR throughout
development to determine interneuron-specific gene expression changes that account for the behavioral
consequences of Evf2 loss. The Kohtz lab previously showed that Evf2 long non-coding RNA (lncRNA)
transcriptional regulation in the developing brain affects inhibitory circuitry in adult hippocampus, and more
recently discovered that Evf2 controls complex behavior, with both beneficial and detrimental effects. At
Middlebury Lizzie developed proficiency in oral and written Spanish, softball, sailing and skiing. In Chicago she
enjoys sailing and looks forward to skiing as much as possible this winter.
Grace Chandler returned to the Hendrix laboratory following graduation from Duke University in May
2014 where she earned a B.A. with high distinction in English, and minor studies in Spanish and Chemistry.
As a summer student in the Hendrix lab in 2013 Grace studied the tumor suppressor gene Maspin, and was
included as a co-author on a subsequent publication in the journal Molecular Cancer Research for her work on
the project. Grace is excited to be back home in Chicago and contributing to a new project – examining the
function of the embryonic morphogen Nodal in breast cancer. Grace hopes to pursue a career in medicine
following her employment at the research institute, and is currently applying to medical school. “Working with
Dr. Thomas Bodenstine in the Hendrix laboratory has given me an improved appreciation for the immense
value of translational research,” Grace expressed. “Although I aspire to become a clinician, I am now much
more likely to devote time to research in medical school and during my career; I hope to continue to explore
Grace Chandler
‘big picture’ medical issues of interest in greater detail.” In her spare time Grace has been an active volunteer in
both clinical and non-clinical settings, including service as a Child Life Volunteer at Lurie Children’s and in the
Pediatric Blood and Marrow Transplant (PBMT) Unit at Duke Hospital. She was also an ESL tutor for Spanishspeaking adults in Durham, NC. Grace continues to volunteer at Lurie Children’s, and recreationally she enjoys
distance running, skiing, hiking, travel and painting.
[Page 3]
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Saving the Sumatran Rhino
Tam, the male rhino, in his
enclosure at Tabin Wildlife Reserve.
Image courtesy of Vasil Galat, PhD.
Among the world’s most endangered
animal species, the Sumatran rhinoceros
has been hunted for its horn and has
suffered the loss of most of its habitat. The
Borneo Rhino Sanctuary (BRS) programme
Agencies involved in the
seeks to prevent the extinction of this
Borneo Rhino Sanctuary
stately herbivore. Fewer than ten are
programme:
known to exist today in Borneo.
Borneo Rhino Alliance
As part of a multi-institutional effort
(BORA), ITBC/Universiti
Malaysia Sabah, Leibniz
Institute for Zoo and Wildlife
Research (IZW) and partners
(Avantea, Friedrich-Loeffler
Federal Research Institute
for Animal Health, Manne
Research Institute, San Diego
Zoo’s Frozen Zoo, Sabah
Forestry Department (SFD),
Sabah Foundation, Sabah
Wildlife Department (SWD),
WWF-Germany, WWFMalaysia, Yayasan Sime Darby.
to save the Sumatran rhino, Vasil Galat, PhD
traveled to Tabin Wildlife Reserve in Borneo during two consecutive years to establish cell cultures from tissue
cells of the rhinos held in captivity at Tabin. Prior to his arrival, BRS had pursued several attempts at assisted
reproductive technology (ART), which resulted in one instance of gamete production. This effort produced
no embryos, and the rhino developed fibrosis, a hormone-related pathology. In order to protect her, the team
shut down her reproductive cycle, with no reproductive options left.
Galat, who is an expert in reproductive technology and embryonic stem cells, was invited by BRS to
develop a novel strategy for saving the species with the help of embryonic-like induced pluripotent stem cells.
The team had obtained a room and brought some basic laboratory equipment from Berlin, including three
microscopes, a centrifuge and a cryo tank. “Because this field lab exists in the middle of a rainforest, I needed
to improvise to create clean conditions. I caused an updraft with alcohol burners to make a clean space in
which to work. In less remote areas, labs are equipped with cabinets whose airflow helps maintain sterility;
transporting such equipment to this area was not possible,” says Galat. The efforts in the first year became
especially important in that it helped to preserve in living cell culture the genome of Gelogob, an older female
who is now deceased. Subsequently, customized portable CO2 incubator and laminar flow box units were
designed in Germany and delivered to the field laboratory.
Next, skin and other tissues were obtained from three rhinos, Tam, Puntung and Iman. The derived cells
Below: Field lab at Tabin. Image
courtesy of Vasil Galat, PhD.
were successfully cultured, initially by Galat at Tabin, then at Friedrich-Loeffler Federal Research Institute for
Animal Health. The cell cultures will be transferred to Leibniz Institute for Zoo and Wildlife Research (IZW)
for maintenance and development of induced pluripotent stem cells (iPSCs) in collaboration with Manne
Research Institute. To allow for possible alternative experimentation in the future, cell lines were also taken
by Oliver Ryder, and are held in San Diego Zoo’s Institute for Conservation Research “Frozen Zoo”. The full
genome of all four rhinos is now preserved.
Galat’s effort to collect cells is an alternative to in vitro fertilization. At present there is no funding for this
work; if funds become available, he can use the skin cells to develop iPSCs. At that point, several ways would
exist to recover the species, including differentiating the cells to sperm and egg, and making an embryo; or
using iPSCs to combine with embryos of other closely related species to produce a chimeric animal capable
of producing gametes of either individual. Says Galat, “I am hopeful that these efforts will be successful. They
are needed, not just for this species but for many other species in the same position. Even if we can’t save
the Sumatran rhino, our techniques could be used to save others.” Galat is Research Assistant Professor of
Pathology at the Feinberg School, director of the iPS and Human Stem Cell Core Facility and a member of the
Developmental Biology Program at the research institute.
[Page 4]
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Publications
iStock photo
Spiral generated in the laboratory
of Philip M. Iannaccone, MD, PhD.
Environmental or lifestyle exposures in utero
further information about these relationships in
may influence the development of childhood
young children is needed. In a study led by John
asthma. A new study published in the journal
Lavigne, PhD, 796 young children were followed
Pediatrics finds that the development of
longitudinally. An ethnically diverse community
asthma in children may be associated with
sample of children was assessed for anxiety and
maternal obesity in pregnancy (MOP) or
depression symptoms. The results indicate that
increased maternal gestational weight gain
anxiety and depression are relatively stable over
(GWG). Rajesh Kumar, MD collaborated with
time. Anxiety at age 4 and 5 was a significant
researchers at the University of Pittsburgh
positive predictor of subsequent depression. While
to conduct a meta-analysis of previously
an inhibitory effect of depression on subsequent
performed observational studies. Their analysis
anxiety was found, that effect was due to negative
concludes that MOP is a significant risk factor for
suppression, and higher levels of depression were
the development of childhood asthma or wheeze,
actually associated with subsequent anxiety.
while GWG may also increase the risk of childhood
Consistent with a significant suppression effect,
asthma or wheeze. These findings may be particularly
when depression was included as a predictor, the
significant for mothers without asthma history.
association between anxiety at ages 4 and 5 and
Given that obesity complicates up to 20 percent of
anxiety one year later increased in magnitude. Both
pregnancies in the United States, and that asthma
anxiety and depression are associated with higher
affects approximately 7 million children in this
levels of one another in the subsequent year. The
country, more information is needed to determine
study is published in the Journal of Abnormal Child
the mechanisms involved in these associations,
Psychology. Lavigne is Professor of Psychiatry and
and to develop strategies to address this major
Behavioral Sciences and Pediatrics at the Feinberg
public health problem. In addition, the significant
School, Chief Psychologist and Medical Psychologist
heterogeneity among existing studies indicates
at Lurie Children’s and a member of the Smith
a need for standardized approaches to future
Child Health Research Program. This research was
studies on the topic. Kumar is Associate Professor
supported by the National Institute of Mental Health.
of Pediatrics at the Feinberg School, an attending
physician in the Division of Allergy and Immunology
at Lurie Children’s and a member of the Mary Ann &
J. Milburn Smith Child Health Research Program of
Manne Research Institute. This study was supported
by the National Institutes of Health (NIH).
John Lavigne, PhD
View a list of all research
institute publications from
September 2014 to the present.
[Page 5]
The outermost layer of the cornea, the corneal
epithelium, consists of cells that can reproduce and
regenerate after an injury. During maturation in
mammals, corneal epithelial cells tend to develop
into patterns such as spirals over time. A better
understanding of these patterns can elucidate
Anxiety and depression tend to co-occur in
how the organ develops and may give insight
children. Studies indicate that higher levels of
into diseases affecting corneal development. In
anxiety are associated with subsequent higher
a Biomechanics and Modeling in Mechanobiology
levels of depression, while depression may inhibit
publication, a group from the University of Illinois
subsequent anxiety. It is important to increase
at Chicago (UIC) and Manne Research Institute
understanding of the temporal sequencing of these
proposed a framework for explaining the spiral
disorders and to determine if suppression effects
patterns due to the effect of tensile and shear strains.
account for the inhibitory association. In addition,
Using animals made by combining embryonic cells
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Publications
(continued)
from genetically distinguishable strains, they observed the development of patterns in the cornea. Aggregates
of cell progeny called patches form as organs and tissue develop. The boundaries of these patches were fitted
with logarithmic spirals on confocal images of adult corneas. The team developed a model for the cornea
under intraocular pressure to examine the strain distribution on the cornea surface. Tracing the directions of
critical strain vectors led to spiral-like curves. Good agreement between the observed and numerical curves
Tony Rankin, Facility Manager
at the research institute, is
the author of an article in ALN
Magazine entitled “Physical Plant
supports the proposed assumption that shear and tensile strains facilitate sliding of epithelial cells to develop
spiral patterns. The studies were done in Philip Iannaccone’s laboratory with postdoctoral fellow Jerry Rhee,
PhD, with further results published in Complexity. Co-investigator Craig Foster, PhD is in the Department of
Civil and Materials Engineering at UIC. Philip M. Iannaccone, MD, PhD is George M. Eisenberg Professor of
Efficiency for Vivariums”. He
Pediatrics at the Feinberg School; Senior Vice President and Deputy Director for Research - Basic Science; and
describes hazards common to
director of the Developmental Biology Program of the research institute. The authors are supported by NIH,
workplace settings and provides
an overview of the systems and
plans in place at the research
institute to control these hazards.
ALN is “the leading source for
today’s research animal facilities,”
according to its website.
the George M. Eisenberg Foundation for Charities and the National Science Foundation. See also “Investigating
Spiral Formation in the Cornea”.
Research Institute Members Promotions and Tenure
Katherine A. Barsness, MD, MS — Associate Professor in Surgery and Medical Education
Anthony C. Chin, MD — Associate Professor in Surgery
Walter J. Eppich, MD, MEd — Associate Professor in Pediatrics-Emergency Medicine and Medical Education
Robert Garofalo, MD, MPH — Professor in Pediatrics-Adolescent Medicine and Preventive Medicine
Stewart Goldman, MD — Professor in Pediatrics-Hematology, Oncology and Stem Cell Transplantation
Zena Leah Harris, MD — Professor in Pediatrics-Critical Care
Nobuko Hijiya, MD — Professor in Pediatrics-Hematology, Oncology and Stem Cell Transplantation
Lawrence J. Jennings, MD, PhD — Associate Professor in Pathology
Janine Y. Khan, MD — Associate Professor in Pediatrics-Neonatology
Mary Beth N. Madonna, MD — Associate Professor in Surgery
Jonathan W. Necheles, MD, MPH — Associate Professor of Clinical Pediatrics-Community-Based Primary Care
Adrienne Prestridge Savant, MD — Associate Professor in Pediatrics-Pulmonary Medicine
Luciana T. Young, MD — Professor in Pediatrics-Cardiology
Comprehensive list of Feinberg School’s recently promoted and/or tenured faculty members.
Peter F. Whitington, MD, director of the Siragusa Transplantation Center at Lurie Children’s and Sally Burnett
Searle Professor of Pediatrics and Medicine at the Feinberg School, will be the recipient of the Shwachman
Award, to be presented at the national meeting of the North American Society for Pediatric Gastroenterology,
photo: Lurie Children’s Audiovisual Department
Hepatology and Nutrition in October, 2014. The Shwachman Award is the most prestigious award given by
the Society to a person who has made major lifelong scientific or educational contributions to the field of
pediatric gastroenterology, hepatology or nutrition in North America. The additional criteria for Shwachman
nominees are a record of advocacy for child digestive diseases, outstanding administrative service to the field
and lifelong scientific or educational contributions to the discipline. Whitington is a member of the Center for
Peter Whitington, MD
[Page 6]
Intestinal and Liver Inflammation Research (CILIR) at the research institute.
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Events News
From Philip Iannaccone, MD, PhD, former director of MSTP:
Northwestern University celebrated the 50th anniversary of its Medical Scientist Training Program (the MD/
PhD program) July 18-19 in conjunction with the NIH celebration for 50 years of National Institute of General
Medical Sciences (NIGMS) support for the program. Northwestern University’s MSTP has been continuously
funded since the inception of the program by the NIGMS. MSTP has been an enormously influential program
and has produced leaders in medical science for its entire existence.
Northwestern University has one of the longest continuously running MSTP programs in the country
and has served in many ways as a model for programs of this type. The first Northwestern MSTP student to
graduate did so in 1928. I was privileged to run the program from 1992 to 1995, and served as its Principal
Investigator. During my tenure we dealt with a range of issues including stabilizing the financial situation,
organizing recruiting and selection of the students, establishing equitable distribution of students to labs on
all campuses, and developing minority recruiting strategies. The program is multi-campus; students work in labs at the Feinberg School, in Evanston and at Lurie
Children’s. MSTP students receive full tuition and a stipend for both degrees, paid for by the grant and the
student’s research mentor. They complete a portion of their medical student studies, followed by work in
several research labs, which helps them select a project and a lab in which to complete their PhD. They begin
scientific course work and then their research project, culminating in a PhD thesis. Following successful
completion of the thesis defense they finish their remaining medical school studies and typically move on
to internship, residency and further clinical training. In many cases, continuing postdoctoral research studies
are also involved. Innovative residency training programs (called fast-track) have been developed which
allow research and clinical training to be combined along with the promise of faculty status at the training
Manley Symposium participants:
Front row: Mo Chen, Vasupradha
Vethantham, Xialu Li, Frida Kleiman,
Carol Prives, Jim Manley, Jhumku Kohtz,
Saba Valadkhan, Kevin Ryan, Kensei
Nishida, Takashi Yamazaki, Xin-Yuan Fu
Back row: Jing-Ping Hsi, Emanuel
Rossonina, Chuck David, Tristan Coady,
Diana Colgan, Masahiro Nogami, Zake
Chen, YongSheng Shi. Among the
distinguished invited speakers (not
pictured) were Gideon Dreyfuss and
Robert Singer.
institution. MSTP students are highly sought after and have gone on to terrific careers. The research institute has hosted several of these students in its labs, including Beth Villavicencio from my
laboratory, and Sara Fossum, a third year student in the laboratory of Ann Harris, PhD. During the annual MSTP
student-faculty retreat this spring, Fossum remarked, “It is great having alumni join us on this year’s retreat.”
She presented on the regulatory roles of the gene EHF in the lungs. “Talking to alumni, I can get an idea of
the different career paths that are available after I finish the program. Also, by talking to different physicianscientists, I get a broad perspective on research happening in other fields.”
Read more about the 50 year celebration.
A symposium honoring James L. Manley, Julian Clarence Levi Professor of the Life
Sciences at Columbia University was held on May 30, 2014. Organized by Jhumku
Kohtz, PhD, alumna of the Manley laboratory, Research Associate Professor of Pediatrics
at the Feinberg School and a member of the Developmental Biology Program of the
research institute, the symposium included colleagues whom Manley has influenced and
mentored over his career. His distinguished contributions to the field of gene regulation,
particularly for mechanistic analysis of transcriptional regulation and RNA processing and
elucidating novel links between them, have been recognized by prestigious awards from
organizations such as the American Association for the Advancement of Science (AAAS)
and the National Academy of Sciences (NAS). Among the symposium speakers were
leaders in the field from Chicago, New York, China, Singapore, Japan and other locations.
[Page 7]
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
In the News
Tissue regeneration using anti-inflammatory nanomolecules
Adapted from EurekAlert! — August 22, 2014
Anyone who has suffered an injury can probably remember the after-effects, including pain, swelling
or redness. These are signs that the body is fighting back against the injury. An inflammatory response
acts as a protective mechanism to enable tissue repair and regeneration. However, the same mechanism
may interfere with healing in situations in which foreign material is introduced. In such cases, the
inflammation may lead to tissue fibrosis, which creates an obstacle to proper physiological function.
The research group of Arun Sharma, PhD has been working on innovative approaches to tissue
Innate immune cell distribution in
regenerating bladder tissue. Elevated
levels of CD68+ macrophages (green) and
MPO+ neutrophils (red). Image courtesy
of Arun Sharma, PhD.
regeneration in order to improve the lives of patients with urinary bladder dysfunction. The team has
developed a system that may protect against the inflammatory reaction that can negatively impact tissue
growth, development and function. Self-assembling peptide amphiphiles (PAs) are biocompatible and
biodegradable nanomaterials that have demonstrated utility in a wide range of settings and applications.
Using an established urinary bladder augmentation model, the group treated a highly pro-inflammatory
biologic scaffold with anti-inflammatory peptide amphiphiles (AIF-PAs). When compared with control PAs, the
treated scaffold showed regenerative capacity while modulating the innate inflammatory response, resulting
in superior bladder function.
This work is published in the journal Biomaterials. Says Sharma, “Our findings are very relevant not just
for bladder regeneration but for other types of tissue regeneration where foreign materials are utilized for
structural support. I also envision the potential utility of these nanomolecules for the treatment of a wide
range of dysfunctional inflammatory based conditions.”
Re-expression of embryonic signaling pathway in melanoma utilizes different receptors than normal
embryonic stem cells
Stanley Manne Children’s Research Institute — September 12, 2014
Metastatic melanoma is a highly aggressive skin cancer whose incidence is on the rise at an alarming rate.
Research has revealed that metastatic tumor cells share similar signaling pathways with embryonic stem
cells to sustain plasticity and growth. However, major regulators of these pathways are often missing in
tumor cells, thus allowing uncontrolled tumor growth and spreading to occur.
photo: Andrew Campbell
Zhila Khalkhali-Ellis, PhD
During early vertebrate development, Nodal, an embryonic growth factor that governs the growth,
pattern and position of tissues, is critical for normal maturation. Nodal plays a significant role in maintaining
the pluripotency of embryonic stem cells — the ability of stem cells to differentiate into any of the three
germ layers that comprise the body. The recent discovery of Nodal’s re-expression in several aggressive
and metastatic cancers has highlighted its critical role in self-renewal and maintenance of the stem celllike characteristics of tumor cells such as melanoma. However, the signaling pathway receptors utilized by
melanoma cells to propagate Nodal’s effect remain(s) mostly anecdotal and unexplored.
The laboratory of Mary J.C. Hendrix, PhD made the novel discovery that embryonic stem cells and
metastatic melanoma cells share a similar repertoire of receptors known as Type I serine/threonine kinase(s),
but diverge in their Type II receptor expression. Further testing indicated that metastatic melanoma cells
and embryonic stem cells use different receptors for Nodal signal transduction. These findings reveal the
divergence in Nodal signaling between embryonic stem cells and metastatic melanoma that can impact new
therapeutic strategies targeting the re-emergence of embryonic pathways in cancer. This work is published in
the International Journal of Cancer and the first author is Zhila Khalkhali-Ellis, PhD.
[Page 8]
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Trainee News
3D printing: innovation, simulation model design and
development
Avi Asher, a senior at Ida Crown Jewish Academy, desires to
pursue an undergraduate major in biomedical engineering,
and this summer he had a unique opportunity to explore
practical applications firsthand in the Innovations Lab at the Feinberg School. Under the mentorship of
innovations design engineer Ellie (Hawkinson) O’Brien, Avi created a three-dimensional model arm for
intravenous insertion to simulate the exact procedure before it is conducted in practice. Avi had previously
attended the program Matter into Medicine: The Biomedical Applications of 3D Printing presented by Katherine
Barsness, MD, MS and sponsored by the Chicago Council on Science and Technology (C2ST), which included
a tour of the Innovations Lab. Impressed with the potential impact of 3D printing on the future of simulationbased medical education and patient care, Avi gratefully pursued the summer internship. Outside of the
classroom Avi enjoys playing high school baseball, writing and editing poetry for the school’s literary
magazine, following favorite sports teams, listening to music and spending time with friends.
by Francine Blazowski
New Training Program director appointed
Philip M. Iannaccone, MD, PhD will serve as director of the Manne Research Institute Training Program,
succeeding Hans-Georg Simon, PhD. The trainees have prospered under the extraordinary leadership of Simon
over the past seven years, and his tireless efforts on their behalf are deeply appreciated. He was instrumental
in encouraging the trainees to attend grant writing workshops, play an active role in organizing themselves
into committees, and coordinate a number of activities which culminated in the annual Biomedical Research
Symposium. Iannaccone is looking forward to the challenges and opportunities for the training program, with
an emphasis on expanding the relationship with clinical trainees. His interactions with Ellen Chadwick, MD, the
Associate Chair for Education, Department of Pediatrics, will be a special focus for the program.
Nehal Gosalia awarded doctorate
Nehal Gosalia, pictured front left, presented her public
defense on July 10, 2014. The title of her presentation was
“CTCF and cohesin have distinct roles in modulating the
higher order structure and expression of the CFTR locus.”
Nehal conducted her graduate research in the laboratory of
Ann Harris, PhD, director of the Human Molecular Genetics
Program of the research institute. A graduate of the Driskill
Graduate Program in Life Sciences, Nehal is continuing
research in the Harris lab.
photo: Jan Terry
Photo: Front row: Nehal Gosalia, Ann Harris, PhD, Zhaolin Zhang,
PhD, Lindsay Stolzenburg. Middle row: Shih-Hsing Leir, PhD, Jenny
Kerschner, PhD, Michael Mutolo, MS, Rui Yang, Sara Fossum. Back
row: Brian Corstange, James Browne.
[Page 9]
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
Robert Louis Katz Summer Scholars
Through the generous support of the Robert Louis Katz Medical Research Foundation, four summer students
at Manne Research Institute received scholarships to nurture their interest in biomedical science. The
foundation, established by Mr. and Mrs. James Katz in memory of their son, Robert, supports scientific and
medical research for diseases in children. The students, known as the Robert Louis Katz Summer Scholars,
are mentored in laboratories of principal investigators who are conducting cutting-edge research in their
respective scientific disciplines. The experience culminates with summary presentations to faculty mentors and
peers, and to the Katz family.
Since 2000 approximately 45 high school, undergraduate and graduate students have benefited from
the generosity of the Katz family. The 2014 Robert Louis Katz Summer Scholars are: Liliana Aguayo, Shawn
Krishnan, Kevin Lindsay-Rivera and Sarah Wachtel. These scholars, their mentors and the entire scientific
community of Manne Research Institute extend a special thank you to the Katz family for their most generous
and unwavering commitment to research and training. Countless lives from patients to future scientists benefit
from their special and thoughtful kindness.
Liliana Aguayo
Mentors: Helen Binns, MD, MPH and Adolfo Ariza, MD
Mary Ann & J. Milburn Smith Child Health Research Program
Project: Quality improvement in obesity care
School: University of Illinois at Urbana-Champaign
Second year of the PhD/MPH program I-TOPP - Illinois Transdisciplinary Obesity Prevention Program
Shawn Krishnan
Mentor: Hans-Georg Simon, PhD
Developmental Biology Program
Project: A new structural and functional role of Pdlim7 in mouse uterus smooth muscle
School: Northwestern University sophomore enrolled in the Weinberg College of Arts and Sciences
Kevin Lindsay-Rivera
Mentors: Maria de Fatima Bonaldo, PhD and M. Bento Soares, PhD
Cancer Biology and Epigenomics Program
Project: Quantitative analysis of DNA methylation in IGF2 imprinted regions in ependymoma tumors
School: Yale University senior
Sarah Wachtel
Returning 2012 Robert L. Katz Summer Scholar
Mentors: Ann Harris, PhD and Michael Mutolo, MS
Human Molecular Genetics Program
Project: Modifier genes that control lung disease severity in cystic fibrosis
School: Northwestern University senior pursuing a double major in Performance Harp and Biology
photos: Jan Terry
[Page 10]
by Francine Blazowski
[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
2014 Summer Students
by Francine Blazowski
Kiren Ali
Laboratory of Jacek Topczewski, PhD
Study of skeletal development in zebrafish
Junior at Loyola University Chicago majoring
in Biology
Maya Behn
Laboratory of Simone T. Sredni, MD, PhD
A zebrafish model for malignant rhabdoid tumors
Freshman at Haverford College majoring in Biology
Sam Buchman
Laboratory of Mary Beth Madonna, MD
Mentor: Fei Chu, MD, PhD
Effects of notch inhibition in the
development of drug resistance of
neuroblastoma
Graduate of Connecticut College with
a degree in Biochemistry, Cellular and
Molecular Biology
Irena Balzekas
Laboratory of Sookyong Koh, MD, PhD
Two hit hypothesis of epileptogenesis:
long term EEG monitoring
Graduate of McGill University with a
degree in Physiology
Kate Cavanaugh
Laboratory of Philip Iannaccone, MD, PhD
Identifying spirals in corneal epithelium following
cell assortment using genetic mosaics
Graduate of Northwestern University with a
degree in Evolutionary and Developmental
Biology
Kate Cavanaugh is currently sponsored in a master’s fellowship
under the Erasmus Mundus Program at five universities throughout
Europe: University of Naples Federico II, Italy; University of Antwerp,
Belgium; University of Veterinary Medicine Vienna, Austria; JustusLiebig University Giessen, Germany; and Poznan University of Life
Sciences, Poland, majoring in Comparative Vertebrate Morphology.
Emily Hayes
Laboratory of Tadanori Tomita, MD
Mentor: Guifa Xi, MD, PhD
Mechanisms of neural stem cell
differentiation
Sophomore at the University of
Rochester majoring in Biochemistry and
Statistics
Rachel Jones
Laboratory of Mary Beth Madonna, MD
Mentor: Fei Chu, MD, PhD
Effects of notch inhibition in the development
of drug resistance of neuroblastoma
Entering the Feinberg School
as an MS1 this fall
Elise Hyser
Laboratory of Mark Wainwright, MD, PhD
Mentor: Chun-Shu Piao, PhD
Role of ACTH in traumatic brain injury
Second year medical student at Edward Via
College of Osteopathic Medicine
Morgan Ketterling
Laboratory of Arun Gosain, MD
Craniosynostosis in the zebrafish model
Senior at the University of Michigan
majoring in Neuroscience, pre-Med
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[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]
2014 Summer Students
Stephan Kienzle
Laboratory of Sookyong Koh, MD, PhD
Effect of maternal care on recovery of
juvenile mice with artificial stimulation
after early-life seizures
Junior at Northwestern University
majoring in Biology and Economics (continued)
Rebecca Lewis
Laboratory of Tadanori Tomita, MD
Mentor: Guifa Xi, MD, PhD
Expression of H3K4me3 in pediatric gliomas
Sophomore at the University of Rochester
majoring in Biomedical Engineering
Ruby Loera
Laboratory of Sookyong Koh, MD, PhD
Effect of maternal care on recovery of pups with
artificial stimulation after early-life seizures
Senior at Augustana College majoring in
Neuroscience with a pre-Occupational Therapy
track and Spanish
Iris Lin
Laboratory of Lauren Pachman, MD
Examination of angiogenesis
factor microRNA-21 expression
in induced pluripotent stem cells
derived from control and juvenile
dermatomyositis patients
Senior at Wellesley College
majoring in Biological Sciences
Sarah Monick
Laboratory of Tadanori Tomita, MD
Mentor: Shekhar Mayanil, PhD
Nuclear translocation of FOLR1 isoforms Senior at the University of Illinois
at Urbana-Champaign majoring in
Molecular & Cellular Biology with a
minor in Chemistry Hamza Mahmood
Laboratory of William Tse, MD, PhD
Cell cycle control and fate determination
in myeloid cell development Freshman at Lake Forest College
majoring in Biology Nina Orwitz
Laboratory of Jhumku Kohtz, PhD
Mentor: Ivelisse Cajigas, PhD
Evf2 long non-coding RNA nuclear
localization and lamins Senior at Northwestern
University majoring in Biological
Sciences with a concentration in
Neurobiology
Amar Shah
Laboratory of Tadanori Tomita, MD
Mentor: Shekhar Mayanil, PhD
The mechanism of folate receptor rescue in NTD
Junior at Northwestern University majoring in
Biology and Economics, pre-Med
Jacob White
Laboratory of Sookyong Koh, MD, PhD
Two hit hypothesis of epileptogenesis: long
term EEG monitoring
Graduate of Case Western Reserve University
with a degree in Biology, pre-Med
Nancy Su
Laboratory of Nikia Laurie, PhD
Analyzing the effects of gene expression
changes on retinoblastoma growth
Sophomore at Northwestern University
majoring in Economics, pre-Med
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[InTouch with Research: Fall 2014]
[Stanley Manne Children’s Research Institute]