Northwestern University Feinberg School of Medicine

Feinberg School of Medicine Research Office July/August 2012

FSM Researcher

Immunosuppression, ctd.

New COI regulations

Welcome new faculty Core fact

Sponsored research

Research in the news

High impact research

Follow Feinberg Online

In this Issue...

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Contact the Feinberg Research Office:

n-mladic@northwestern.edu

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Student profile6

Faculty profile: Seth Corey, MD, MPH

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Events Funding

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Delayed Tolerance May Hold Key to Life without ImmunosuppressionThree years after Joseph Leventhal, MD, PhD, director of kidney and pancreas trans-plantation, performed the first of more than a dozen groundbreaking simultaneous kidney-stem cell transplants in mismatched donor-recipient pairs, an upcoming clinical trial could someday change the way all transplants are done in the future.

In collaboration with Suzanne Ildstad, MD, director of the Institute of Cellular Therapeutics at the University of Louisville, the pending trial is an adaptation of their ongoing research published this year in Science Translational Medicine.

The paper outlined a modified transplant procedure that begins about a month before a kidney transplant, when bone marrow stem cells are collected from the blood of the kidney donor using a process known as apheresis. The donor cells are then sent to the University of Louisville, where researchers enrich cells believed to help transplants succeed. During the same time period, the recipient undergoes pre-transplant condi-tioning, which includes small doses of radiation and chemotherapy to suppress their own bone marrow, so the donor’s stem cells have more space to grow in the recipient’s body.

A day after the kidney transplant, the donor stem cells are transplanted as well, prompting them to engage in the marrow, from which other specialized blood cells develop. The goal of the double-transplant technique is to create chimerism, or an en-vironment where two bone marrow systems exist and function in one person. Following transplantation, the recipient takes anti-rejec-tion drugs, with the goal of decreasing them

Joseph Leventhal, MD, PhD, consults with a participant during a groundbreaking study proving life without immunosupression may be possible for transplant recipients.

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over time and eliminating them altogether one year after the procedure.

Normally, organ recipients must follow a lifelong regimen of immunosuppressant drugs for their transplanted organs to survive. Those drugs greatly increase the risk of infec-tions, cancer, high blood pressure, and other serious medical problems.

By tricking the recipients’ immune system into thinking the donated organ is part of the patient’s natural self, the pro-cedure has thus far eliminated the need for the medication years after transplantation.

“Our third patient was the first where we had the engineered stem cell dose that we wanted, given the full condition-ing regimen, and saw this high level of chimerism that was persistent,” said Leventhal, associate professor of surgery at Northwestern University Feinberg School of Medicine. “We were a year out, and when he came off of immunosup-pression it was, ‘oh my god, we’ve done it.’ Because it was a living, unrelated transplant, a friend to a friend, it was almost surreal that we had been able to demonstrate proof of principle.”

What Next?Leventhal and Ildstad expect to begin new research this year that could potentially change the way all transplants are conducted.

“We are ready to embark on a companion clinical trial of what we are calling ‘delayed-tolerance induction,’ where we postpone the infusion of the donor stem cells until months or even years after the transplant occurs,” Leventhal said. “This is an important trial conceptually because this is the manner in which researchers will very most likely achieve tolerance for deceased-donor organs.”

Because the process of recipient conditioning and transplan-tation takes four to five days, it is impossible to conceive a timeframe where it could be used for other solid organ pro-cedures. But much the way Leventhal and Ildstad built the mismatched donor trial from Ildstad’s preclinical and early clinical observation, delayed-tolerance induction is building upon the most recent mismatched-donor successes.

“When you have a deceased donor organ like a kidney, a liver, or a heart, you don’t have four to five days to get that organ; you maybe have four to five hours. You need an ap-proach that is going to separate the transplant from the ac-tual induction of tolerance using stem cells,” Leventhal said. “If this trial is successful, it really opens the door to use a modification of our approach in practically any organ trans-plant scenario. It’s pretty exciting.”

The new delayed-tolerance trial will involve individuals who

received a living-donor kidney, and whose donor is ready, willing, and able to provide stem cells down the road. The procedure will test the concept of separating the transplant event from the stem cell infusion and tolerance induction.

By waiting for an organ recipient to fully recover from the transplant surgery before introducing a tolerance regimen, Leventhal believes the approach will not only open itself to applications with cadaver donors, but that it may become the preferred order of operation even for healthier or living-donor transplants.

“If someone is very sick and is going to have a very stormy post-operative course, the last thing you want to do is induce tolerance in the middle of a hurricane. What you want to do is let that storm pass, let them recover from the organ trans-plant,” he said. “Because they will be in much better shape and no longer be in full-blown liver failure, the tolerance induction will have a greater chance of success.”

Achieving ToleranceTwo years after successfully removing the first mismatched transplant recipient from immunosuppression drugs, Leventhal hopes to validate the single-center approach in a multi-center fashion. Although the results look very prom-ising thus far, the emphasis of the procedure is improving long-term outcomes, something only time will demonstrate.

“We clearly have established for the first time, here at Northwestern, the ability to achieve tolerance in mismatched and unrelated donors and recipients, but there are other cell populations that we know are important for regulating the immune response whose properties can be harnessed and used in the clinic,” Leventhal said. “There are some of us, myself included, who believe that it will be possible to isolate and expand these cells from a potential transplant recipient, and give them back to them after a transplant, which would then allow you to minimize, if not eliminate the drug-based therapy.”

Immunosuppression continued from pg. 1

Suzanne Ildstad, MD, and Joseph Leventhal, MD, PhD

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Revisions to the 1995 Public Health Service (PHS) regulations regarding financial conflict of interest (COI) in publicly funded research, enacted by the Department of Health and Human Services (HHS) in 2011, will be effective on August 24.

Among the most impactful changes are revisions to the definition of “sig-

nificant financial interest,” extent of investigators’ disclosure of information to institutions regarding their financial inter-ests, institutions’ management of financial conflicts of inter-est, information reported to NIH and other funders, informa-tion made available to the public, and investigator training.

Ahead of these revisions, Northwestern University Provost Dan Linzer sent a statement informing the community that as of Monday, July 23, Northwestern had implemented its own new COI policy. He noted that the last time the Northwestern policy and procedures were rewritten was over a decade ago, and that much has changed in the intervening years.

“The new PHS requirements, which we hear may be adopted in part or wholly by other agencies, provided impetus to re-visit our COI policies and procedures,” he said in the state-ment. “The policy changes are being implemented to comply with new federal regulations governing Financial Conflict of Interest (FCOI) policies at all institutions accepting PHS re-search funds.”

The new Northwestern policy and process will apply to all individuals involved in the design, conduct, or reporting of research for all proposals submitted and current awards re-ceived on or after August 24. While all research investigators will be affected by the new Northwestern COI policy, PHS funded researchers and staff working on PHS-funded studies will have additional disclosure requirements.

Further information about the new Northwestern University COI policy can be found on the Conflict of Interest Office (NUCIO) website.

What you need to know about the PHS regulations

• As Linzer noted, the PHS regulations may affect all agencies funded under HHS. Says Michelle Melin-Rogovin, manager of research administration at Northwestern University Feinberg School of Medicine, “The NIH guidance is probably good for sister agencies that are smaller and less structured to follow. Also, as goes PHS, so goes the federal government; the National Science Foundation has similar guidelines, so don’t think you’re off the hook.” Melin-Rogovin has been writ-ing about the new guidelines in her blog, “Research Administration Nation.”

• The Feinberg Research Office recommends checking the NIH website FCOI page for new information at least weekly.

• Melin-Rogovin also recommends bookmarking the NIH frequently asked questions section about the regulations – new questions are added regularly.

• Research administrators should be prepared to ask PIs about planned travel and its purpose – creating a check-list of items to ask about, depending on the investiga-tor’s type of research activity, will be important.

Melin-Rogovin adds, “Collaboration between industry and academia is needed in order to fund advancement in sci-ence. Not every relationship is a conflict of interest, and these relationships can be extremely complicated. If you have a question, it’s perfectly appropriate to ask about it in order to receive additional information and to understand that the project you’re working on is meeting your university guidelines and the new regulations.”

Presentation slides and a handout from the July town hall meeting regarding the new PHS regulations and Northwestern COI policy are available on the NUCIO website. General questions and inquiries about the new policy should be directed to nucio@northwestern.edu.

New PHS Research Conflict of Interest Regulations

Because immunosuppression drug regiments require rigor-ous compliance, produce side-effects which limit life expec-tancy, and do not prevent the chronic loss of organs over time, Leventhal is hopeful that tolerance induction will make a major impact.

“We believe that the quality of life that patients will experi-ence and how long their organs will last will be enhanced by coming off of drug-based immunosuppression,” he said. “I think it’s safe to say that over the next decade there is going to be a tremendous amount of work where we begin to iden-tify new cell-based strategies that have the broadest applica-tion for improving outcomes in organ transplant recipients.”

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Working at the intersection of pediatrics and ba-sic science, Seth Corey, MD, MPH, professor in pedi-atrics and cell and molecular biol-ogy at Feinberg, is one investigator whose transla-tional research will

benefit from the new location of Anne and Robert H. Lurie Children’s Hospital of Chicago.

Prior to joining Northwestern University in 2008, Corey was section chief of pediatric leukemia and lymphoma at University of Texas MD Anderson Cancer Center. He also was associate professor of pediatrics and pharmacology at University of Pittsburgh School of Medicine.

He received his medical degree and master’s degree in public health in 1982 at Tulane University. He completed his residency at the St. Louis Children’s Hospital in pediat-rics in 1985 and his fellowship in pediatrics hematology at Children’s Hospital in Boston in 1988.

In recent years, Cory has published papers in Blood, Current Biology, Cancer Research, Oncogene, Journal of Cell Sciences, Journal of Biological Chemistry, and Clinical Cancer Research.

When not pursuing his career-related passions, Corey is a film buff. During his time at the University of Pittsburgh he started a film festival to showcase the emerging Israeli film industy. Though Corey is no longer involved, the popular fes-tival lives on, and is now in its 20th successful year.

What are your research interests?

I am interested in why white blood cells become leukemic, and why the bone marrow fails to produce normal blood cells. Each day a trillion blood cells are produced, yet leukemia is not as common as epithelial

cancers, and bone marrow failure syndromes are rare. There must be tight, high-quality systems that control for the prolif-eration, differentiation, and survival of blood stems cells and their progeny.

My lab focuses on two fascinating sets of disorders, the adult myelodysplastic syndromes and the pediatric bone marrow failure syndromes. Both evolve frequently into leukemia.

A second major project in our lab focuses on how a protein we discovered remodels both the plasma membrane and the actin cytoskeleton.

The ultimate goal is to understand the mysteries of biological systems and contribute to the cure of children and adults af-flicted with leukemia or myelodysplastic syndromes.

Who makes up your research team?

I have a small but diverse group of people, which makes the lab fun: a biochemist, a couple physician-scientists, two technicians, a zebrafish biologist and his technician, and this summer a great group of enthusiastic undergraduates and graduate students.

How does the Lurie Children’s move affect your work?

The move has made it easier for me to participate more fully in clinical activities and education, and will hopefully allow my colleagues to interact more with me in translational re-search. It now takes a village to care for a patient, study his or her disease, and advance knowledge. Lurie Children’s is no longer a suburb.

How does your research advance medical science and knowledge?

First, one has to identify the components. To understand the pathophysiology of blood disorders, I began my career as a fellow in the new field of oncogene signaling. I identified and characterized the roles of Src tyrosine kinases and PI 3’kinase and their associated signaling molecules in hematopoiesis and leukemia.

Then, in collaboration with pharmaceutical companies, my lab showed that inhibitors of Src or PI 3’ kinases block leukemia (and solid tumors like breast cancer). Successful targeted therapy, however, will not be easy, as biological systems are complex and resistance comes quickly.

Now, I am working with a bioengineer and a mathematician on a systems analysis of how a blood stem cell becomes specialized like a neutrophil and where the system can fail to produce too few or too many cells. Ultimately, I’d like to use that analysis as a blueprint for systems pharmacology against leukemia and myelodysplastic syndromes.

What collaborations are you involved with across campus and beyond?

Science is a team sport, and

Faculty Profile: Seth Corey, MD, MPH Professor in Cell and Molecular Biology and Pediatrics

Q&A

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it requires multi-disciplinary skills. My current collabora-tions are with a chemical bioengineer at the University of Pennsylvania, a mathematician specializing in stochasticity at Rice University, a bioengineering group at Georgia Institute of Technology, a theoretical chemist at University of Chicago, and a leukemia geneticist in Cleveland. I just wish we could put together such a group here at Northwestern; I firmly be-lieve in the inverse-square law.

How is your research funded?

I have been continuously funded since 1988, mostly through the National Institutes of Health. But grants from American Heart Association, American Cancer Society, Leukemia and Lymphoma Society, Department of Defense, Howard Hughes Medical Institute, and foundations like Hyundai Hope for Wheels have sustained my research.

How did you become interested in this area of research?

Like biology, it was a little bit of determinism and stochas-ticity. I became interested in immunology during my second year of medical school, when my father died from renal cell cancer, and at that time, the one idea was to use immuno-therapy. I was able to spend three months at the NIH as a fourth year student doing immunology. But as a resident at St. Louis Children’s Hospital, I took care of a girl with severe aplastic anemia. That set off a burning interest in hematopoi-esis and related disorders. I was fortunate to be a post-doc in Boston, in labs where blood growth factors and oncogenes were being discovered.

Now, what interests me is the application of computational biology, engineering, and network analysis to solve these same biomedical challenges.

Which honors are you most proud of?

I am honored to hold an endowed professorship named after Sharon Murphy, former division chief of pediatric hematolo-gy-oncology at Lurie Children’s and past chair of the multi-institutional Pediatric Oncology Group, and Steve Rosen, the Director of the Lurie Comprehensive Cancer Center. Sharon and Steve have been major leaders in clinical oncol-ogy and have made major contributions to the treatment of lymphomas.

Corey, continued from pg. 4

Welcome New FacultyJuehua Gao, MD, PhD, joins as as-sistant professor in pathology.

Gao received her Doctor of Medicine degree from Fudan University in Shanghai, China, where she also completed her internship in internal medicine. She received her doctorate degree in immunology from University of Florida, and completed fellowships in anatomic and clinical pathology

and hematopathology from Feinberg.

Gao’s research interests are signaling and genetic abnor-malities in myeloid neoplasms, particularly in develop-ing clinical assays that provide diagnostic and prognostic value for patients with myelodysplastic syndrome and acute myeloid leukemia.

Hyewon Phee, PhD, joins as assistant professor in microbiology-immunology.

Phee received her bachelor’s de-gree in food and nutrition and her master’s degree in chemistry from Seoul National University, Korea. She then received her doctorate degree in biochemistry from Ohio State University, and completed a post-doctoral fellowship. From

Ohio, she moved to California to finish her post-doctoral work at University of California San Francisco, where she later worked as an instructor and most recently as an as-sistant adjunt professor of medicine-rheumatology.

Phee’s research focuses on signal transduction path-ways in T cell migration, activation, and autoimmunity. Her long-term research goal is to define signal transduc-tion pathways that integrate cytoskeleton and signaling network during immune cell migration and activation in normal and pathological conditions.

Did you know the Keratinocyte Core, part of the Skin Disease Research Center, is offering free services for the summer?

Interested users can download this free coupon to take advantage of limit-ed-time offers, such as free primary keratinocyte cultures.

For more information about the Core’s services, contact Paul Hoover at paul-hoover@northwestern.edu.

Core Fact

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When Theresa Sukal Moulton, DPT, PhD, ar-rived at Northwestern University to pursue her master’s degree in the fall of 2003, the doctor in physical therapy-doctor of philosophy in engineering dual-degree program, of which she would become the first graduate, didn’t even exist.

But while working in the lab of Jules Dewald, PT, PhD, chair of the Department of Physical Therapy and Human Movement Sciences

(DPTHMS), as a biomedical engineering graduate student, Sukal Moulton realized a stark interest in understanding what happens in adults following a stroke.

Her pursuit coincided with Dewald’s drive to begin offering a first-of-its kind program meshing the distinct intellect of an engineer with the applied science skills of a physical thera-pist. So in 2006, she began physical therapy (PT) school to help gain a bigger-picture vantage point.

“I think that having clinical experience really improved the research questions I was asking and my ability to carry out successful experiments with young people,” said Sukal Moulton, who decided to focus on pediatrics for her PhD research. “It was a very natural flow to start the DPT-PhD program because it was around the time when I was trying to figure out how I could gain practical, hands-on experi-ence in the clinic.”

Her doctoral dissertation focused on the use of engineering tools to quantify the expression of upper-extremity weak-ness, loss of independent joint control, and loss of indepen-dent limb control in childhood hemiparesis, or weakness affecting one side of the body. The results of her research are noted for illustrating that the timing of brain injuries in infants and young children affect the movement disorders observed and measured in adolescence.

She started by identifying children as having brain inju-ries during three distinct time periods. The first was pre-natal injury, often occurring in babies born prematurely, between the second and early third trimester of gestation.

The second was perinatal injury, occurring at full-term birth, possibly due to a difficult delivery. The last group consisted of those who suffered a post-natal injury, occurring some-time after six months of age.

Sukal Moulton used three different arm strength and coordi-nation experiments to test her hypothesis that the timing of injury mattered with regard to normal development. The first looked at strength, comparing the hemiparetic, or weaker, arm with the stronger arm. The results conveyed that indi-viduals with hemiparesis were weaker on their paretic side, but that the time of the injury affected how much weaker they were. The later the injury, the more weakness was found. And with regard to joint weakness, the further the joint is from the body, comparing the shoulder to the wrist for instance, the greater the weakness.

“We think that part of the reason for that weakness is the neural tissue that’s available at the different time periods of development,” Sukal Moulton said.

The second experiment was based around Dewald’s research in individuals with stroke in adulthood. It looked at move-ment interactions in an isometric setup.

“We used a light weight cast to connect someone to a six-degree-of-freedom load cell. This provided a way for us to very specifically measure the efforts they were making. As we asked them to do a movement exercise in one direction, we looked at what happened with the other joints in their arm.”

She found that while people can normally lift up at the shoulder without other joint involvement, people with hemi-paresis demonstrate different patterns of activation, espe-cially in the post-natal group. When asked to lift up at the shoulder, they also flexed and bent in at their elbow, and flexed and bent their wrist and fingers.

The early injury groups did not have this same loss of in-dependent joint control. If asked to lift their shoulder, they had a normal response, but if asked to lift their wrist as hard as they could, they would also flex their elbow.

“If you look at a lot of the childhood hemiparesis research, anyone with cerebral palsy or hemiplegic cerebral palsy is grouped into one category. Researchers asked individuals to do tasks and generalized by saying ‘kids with cerebral palsy do this, and typically developing kids do this,’ ” Sukal Moulton said. “What my work showed is that maybe you need to look at kids with cerebral palsy in more than one pool, and that the timing of

Student Profile: Theresa Sukal Moulton, DPT, PhD Feinberg’s First DPT-PhD(Eng) Graduate

For Theresa Sukal Moulton, DPT/PhD (Eng) ’12, life is all about timing.

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Peter Penzes, PhD Associate Professor in Physiology and Psychiatry and Behavioral Sciences

Project title: Molecular Mechanisms of Abnormal Dendritic Spine Plasticity in Schizophrenia

Sponsor: National Institute of Mental Health

Schizophrenia is a serious mental disorder which affects approximately 0.5 percent of the population. Strong evidence supports a key role for abnormal synaptic connectivity in schizophrenia, but the molecular mechanisms underlying its pathogenesis are not known. Understanding these mechanisms will allow us to identify new targets for therapeutic intervention, especially early in the course of illness.

Several schizophrenia susceptibility genes regulate synapses and many regulators of synapses are implicated in schizo-phrenia. However, the mechanisms through which mutations in these genes underlie specific neurobiological pheno-types related to schizophrenia are not known. Based on our preliminary data, we hypothesized that rare coding vari-ants in genes that control synapses, cumulatively enriched in subjects with schizophrenia, disrupt brain connectivity, and impact neuromorphological and cognitive measures in patients.

In the proposed work, we will use a multidisciplinary trans-lational approach that combines human genetics, molecu-lar and electrophysiological studies in cellular models,

functional validation in mice, and cognitive assessment and structural brain imaging in patients. Data generated will pro-vide new mechanistic insights into pathways that underlie abnormal brain connectivity in schizophrenia that will allow us to identify therapeutic targets.

Brian Mustanski, PhD Associate Professor in Medical Social Sciences

Project title: Gene-Environment Interactions Effects on HIV Risk (GENI)

Sponsor: National Institute on Drug Abuse

Risky behaviors, specifi-cally substance use, con-duct problems, and sexual risk-taking, are the primary

direct and indirect causes of morbidity and mortality among adolescents. Although these behaviors are often studied individually, research indicates that they frequently occur together, although more information is needed regarding the relationships among and development of these behaviors over time in different populations.

GENI focused on the clustering of these three types of risky behaviors in a very low-income African-American popula-tion of adolescents in the southern U.S. This population is at an increased risk compared to other ethnic, geographic, and income groups for several types of negative mental and physical health outcomes, including victimization due to

injury really makes a difference.”

In front of an audience of friends, family, peers, and profes-sionals, Sukal Moulton defended her dissertation in January, outlining the research that also showed that in terms of controlling a single arm, the later the injury, the harder it became, but when it came to controlling both arms in an in-dependent, non-mirrored fashion, the earlier the injury, the harder that task became.

“We identified two specific areas of movement impair-ment and discovered that it truly depended on the timing of injury,” she said. “It was a really awesome opportunity to open up a new facet of investigation within Dewald’s lab. I

think everybody does that in their own way, but when you work with a totally different population it is very obvious. It was a great experience because I had to convince all of these people working on research with adults that we cannot expect the same from kids and that we need to approach this differently, even if we are using similar techniques to measure them.”

Sukal Moulton, who had been working as a pediatric PT at the Rehabilitation Institute of Chicago, is now headed to Washington, D.C., to begin a post-doctoral fellowship in the lab of Diane Damiano, PT, PhD, at the National Institutes of Health. There she will investigate the coordination of lower extremities in children with cerebral palsy using non-inva-sive brain imaging.

Sukal Moulton, continued from pg. 6

Sponsored Research

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violence, HIV infection, incarceration, and death at an early age. This analysis draws on bioecological theory and prob-lem behavior theory to explain the clustering of substance use, conduct problems, and risky sex behaviors from early to late adolescence.

GENI is led by Mustanski and involves collaborations with Danielle Dick, PhD, Virginia Commonwealth University, and John Bolland, PhD, University of Alabama. In addition to ex-amining the development of a cluster of health issues facing urban African-American youth living in poverty, this study capitalizes on a natural experiment in which federal hous-ing funds were used to relocate a sample of predominantly African-American families living in impoverished public housing to more advantaged neighborhoods. In addition to this “treatment condition,” two natural control groups ex-ist: youth living in other public housing neighborhoods that are equivalent on census measures of poverty and youth self-reported HIV risk behaviors; and youth that relocated to similarly disadvantaged neighborhoods.

What makes this natural experiment particularly exceptional is that all of these adolescents (592 adolescents between the ages of 13 and 18) were participants in the Mobile Youth Survey (MYS), which provides multiple waves of pre-relocation youth self-report data on HIV risk behaviors and neighborhood quality. Along with census data, the MYS data allows for statistical control for baseline differences between groups. To extend the MYS data, detailed assessments of sexual risk taking, substance use, externalizing behaviors, neighborhood risks and resources, family factors, and per-sonality were obtained from youth and their primary caregiv-ers. DNA samples for genotyping were also collected.

To help assure that we were addressing concerns and needs of the community participating in the project, we conducted focus groups with neighborhood residents and held a forum with community leaders. Consultation with community advi-sors occurred throughout the project. As a benefit to par-ticipants, a brief HIV education session was provided to the participant family at the completion of their interviews.

Once data collection was complete, Mustanski and the Mobile project team met with community leaders and orga-nization representatives to discuss preliminary analyses and data availability to the community to assist with current and future program planning and grant writing in such areas as teen pregnancy, HIV/AIDS prevention, and mental health.

Analyses are ongoing to identify gene-environment interplay related to this cluster of outcomes. Specifically Mustanski’s team is using caregiver report of neighborhoods, interview assessments, and administrative data to characterize neigh-borhood environments. Neurotransmitter genes and those related to stress response are serving as initial candidate genes.

Sponsored Research, continued from pg. 7 Research in the NewsChicago Tribune July 24 Length of Sleep Varies by Race, Study Shows Mercedes Carnethon’s research was featured.

NBC News (National) July 23 Transplanted Lungs Didn’t Come from Colo. Victims, Despite Reports John Friedewald was quoted.

The New York Times July 19 The New Old Age Lee Ann Lindquist was quoted.

► Lindquist was also quoted in U.S. News & World Report, ABC News (National), and UPI

ABC News (National) July 18 Prostate Cancer: Surgery Rarely Best, Researcher Suggests William Catalona was quoted.

WTTW-Chicago (PBS) July 17 A Condition of Doubt Catherine Belling was interviewed.

► Belling was also quoted in U.S. News & World Report, Huffington Post, and Chicago Tribune

UPI July 13 Reducing Stress Reduced MS Development David Mohr’s research was featured.

► Mohr was also quoted in U.S. News & World Report, WebMD, FOX News National, and UPI

National Public Radio July 11 Gene Mutation Offers Clue For Drugs To Stave Off Alzheimer’s Robert Vassar’s research was featured.

Chicago Tribune July 8 Early Birth Linked to an Increase in Psychiatric Illness Ann Borders’ research was featured.

ABC News (National) July 3 Gene-Altering Lotion May Treat Skin Diseases Amy Paller’s research was featured.

More headlines

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High Impact Factor Research May and June 2012Bankston JR, Camp SS, Dimaio F, Lewis AS, Chetkovich DM, Zagotta WN. Structure and stoichiometry of an accessory sub-unit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels. Proceedings of the National Academy of Sciences U S A. 2012 May 15;109(20):7899-904.

Eisenberg DT, Hayes MG, Kuzawa CW. Delayed paternal age of reproduction in humans is associated with longer telo-meres across two generations of descendants. Proceedings of the National Academy of Sciences U S A. 2012 Jun 26;109(26):10251-6.

Ethier C, Oby ER, Bauman MJ, Miller LE. Restoration of grasp following paralysis through brain-controlled stimulation of muscles. Nature. 2012 May 17;485(7398):368-71.

Hauner KK, Mineka S, Voss JL, Paller KA. Exposure therapy triggers lasting reorganization of neural fear processing. Proceedings of the National Academy of Sciences U S A. 2012 Jun 5;109(23):9203-8.

Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, Creasy HH, Earl AM, FitzGerald MG, Fulton RS, Giglio MG, Hallsworth-Pepin K, Lobos EA, Madupu R, Magrini V, Martin JC, Mitreva M, Muzny DM, Sodergren EJ, Versalovic J, Wollam AM, Worley KC, Wortman JR, Young SK, Zeng Q, Aagaard KM, Abolude OO, Allen-Vercoe E, Alm EJ, Alvarado L, Andersen GL, Anderson S, Appelbaum E, Arachchi HM, Armitage G, Arze CA, Ayvaz T, Baker CC, Begg L, Belachew T, Bhonagiri V, Bihan M, Blaser MJ, Bloom T, Bonazzi V, Brooks J, Buck GA, Buhay CJ, Busam DA, Campbell JL, Canon SR, Cantarel BL, Chain PS, Chen IM, Chen L, Chhibba S, Chu K, Ciulla DM, Clemente JC, Clifton SW, Conlan S, Crabtree J, Cutting MA, Davidovics NJ, Davis CC, DeSantis TZ, Deal C, Delehaunty KD, Dewhirst FE, Deych E, Ding Y, Dooling DJ, Dugan SP, Dunne WM, Durkin A, Edgar RC, Erlich RL, Farmer CN, Farrell RM, Faust K, Feldgarden M, Felix VM, Fisher S, Fodor AA, Forney LJ, Foster L, Di Francesco V, Friedman J, Friedrich DC, Fronick CC, Fulton LL, Gao H, Garcia N, Giannoukos G, Giblin C, Giovanni MY, Goldberg JM, Goll J, Gonzalez A, Griggs A, Gujja S, Haake SK, Haas BJ, Hamilton HA, Harris EL, Hepburn TA, Herter B, Hoffmann DE, Holder ME, Howarth C, Huang KH, Huse SM, Izard J, Jansson JK, Jiang H, Jordan C, Joshi V, Katancik JA, Keitel WA, Kelley ST, Kells C, King NB, Knights D, Kong HH, Koren O, Koren S, Kota KC, Kovar CL, Kyrpides NC, La Rosa PS, Lee SL, Lemon KP, Lennon N, Lewis CM, Lewis L, Ley RE, Li K, Liolios K, Liu B, Liu Y, Lo CC, Lozupone CA, Lunsford R, Madden T, Mahurkar AA, Mannon PJ, Mardis ER, Markowitz VM, Mavromatis K, McCorrison JM, McDonald D, McEwen J, McGuire AL, McInnes P, Mehta T, Mihindukulasuriya KA, Miller JR, Minx PJ, Newsham I, Nusbaum C, O’Laughlin M, Orvis J, Pagani I, Palaniappan K, Patel SM, Pearson M, Peterson J, Podar M, Pohl C, Pollard KS, Pop M, Priest ME, Proctor LM, Qin X, Raes J, Ravel J, Reid JG, Rho M, Rhodes R, Riehle KP, Rivera MC, Rodriguez-Mueller B, Rogers YH, Ross MC, Russ C, Sanka RK, Sankar P, Sathirapongsasuti J, Schloss JA, Schloss PD, Schmidt TM, Scholz M, Schriml L, Schubert AM, Segata N, Segre JA, Shannon WD, Sharp RR, Sharpton TJ, Shenoy N, Sheth NU, Simone GA, Singh I, Smillie CS, Sobel JD, Sommer DD, Spicer P, Sutton GG, Sykes SM, Tabbaa DG, Thiagarajan M, Tomlinson CM, Torralba M, Treangen TJ, Truty RM, Vishnivetskaya TA, Walker J, Wang L, Wang Z, Ward DV, Warren W, Watson MA, Wellington C, Wetterstrand KA, White JR, Wilczek-Boney K, Wu Y, Wylie KM, Wylie T, Yandava C, Ye L, Ye Y, Yooseph S, Youmans BP, Zhang L, Zhou Y, Zhu Y, Zoloth L, Zucker JD, Birren BW, Gibbs RA, Highlander SK, Methé BA, Nelson KE, Petrosino JF, Weinstock GM, Wilson RK, White O. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14.

Jeon SM, Chandel NS, Hay N. AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature. 2012 May 9;485(7400):661-5.

Kaur S, Sassano A, Majchrzak-Kita B, Baker DP, Su B, Fish EN, Platanias LC. Regulatory effects of mTORC2 complexes in type I IFN signaling and in the generation of IFN responses. Proceedings of the National Academy of Sciences U S A. 2012 May 15;109(20):7723-8.

Khazaie K, Zadeh M, Khan MW, Bere P, Gounari F, Dennis K, Blatner NR, Owen JL, Klaenhammer TR, Mohamadzadeh M. Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proceedings of the National Academy of Sciences U S A. 2012 Jun 26;109(26):10462-7. Continued on pg. 10

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Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, Fontana GP, Dewey TM, Thourani VH, Pichard AD, Fischbein M, Szeto WY, Lim S, Greason KL, Teirstein PS, Malaisrie SC, Douglas PS, Hahn RT, Whisenant B, Zajarias A, Wang D, Akin JJ, Anderson WN, Leon MB; PARTNER Trial Investigators. Two-year outcomes after transcatheter or surgical aortic-valve replacement. New England Journal of Medicine. 2012 May 3;366(18):1686-95.

Laurie CC, Laurie CA, Rice K, Doheny KF, Zelnick LR, McHugh CP, Ling H, Hetrick KN, Pugh EW, Amos C, Wei Q, Wang LE, Lee JE, Barnes KC, Hansel NN, Mathias R, Daley D, Beaty TH, Scott AF, Ruczinski I, Scharpf RB, Bierut LJ, Hartz SM, Landi MT, Freedman ND, Goldin LR, Ginsburg D, Li J, Desch KC, Strom SS, Blot WJ, Signorello LB, Ingles SA, Chanock SJ, Berndt SI, Le Marchand L, Henderson BE, Monroe KR, Heit JA, de Andrade M, Armasu SM, Regnier C, Lowe WL, Hayes MG, Marazita ML, Feingold E, Murray JC, Melbye M, Feenstra B, Kang JH, Wiggs JL, Jarvik GP, McDavid AN, Seshan VE, Mirel DB, Crenshaw A, Sharopova N, Wise A, Shen J, Crosslin DR, Levine DM, Zheng X, Udren JI, Bennett S, Nelson SC, Gogarten SM, Conomos MP, Heagerty P, Manolio T, Pasquale LR, Haiman CA, Caporaso N, Weir BS. Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nature Genetics. 2012 June;44(6):642-50.

Lin Z, Yang H, Kong Q, Li J, Lee SM, Gao B, Dong H, Wei J, Song J, Zhang DD, Fang D. USP22 Antagonizes p53 Transcriptional Activation by Deubiquitinating Sirt1 to Suppress Cell Apoptosis and Is Required for Mouse Embryonic Development. Molecular Cell. 2012 May 25;46(4):484-94.

Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu CT, Bielak LF, Prokopenko I, Amin N, Barnes D, Cadby G, Hottenga JJ, Ingelsson E, Jackson AU, Johnson T, Kanoni S, Ladenvall C, Lagou V, Lahti J, Lecoeur C, Liu Y, Martinez-Larrad MT, Montasser ME, Navarro P, Perry JR, Rasmussen-Torvik LJ, Salo P, Sattar N, Shungin D, Strawbridge RJ, Tanaka T, van Duijn CM, An P, de Andrade M, Andrews JS, Aspelund T, Atalay M, Aulchenko Y, Balkau B, Bandinelli S, Beckmann JS, Beilby JP, Bellis C, Bergman RN, Blangero J, Boban M, Boehnke M, Boerwinkle E, Bonnycastle LL, Boomsma DI, Borecki IB, Böttcher Y, Bouchard C, Brunner E, Budimir D, Campbell H, Carlson O, Chines PS, Clarke R, Collins FS, Corbatón-Anchuelo A, Couper D, de Faire U, Dedoussis GV, Deloukas P, Dimitriou M, Egan JM, Eiriksdottir G, Erdos MR, Eriksson JG, Eury E, Ferrucci L, Ford I, Forouhi NG, Fox CS, Franzosi MG, Franks PW, Frayling TM, Froguel P, Galan P, de Geus E, Gigante B, Glazer NL, Goel A, Groop L, Gudnason V, Hallmans G, Hamsten A, Hansson O, Harris TB, Hayward C, Heath S, Hercberg S, Hicks AA, Hingorani A, Hofman A, Hui J, Hung J, Jarvelin MR, Jhun MA, Johnson PC, Jukema JW, Jula A, Kao WH, Kaprio J, Kardia SL, Keinanen-Kiukaanniemi S, Kivimaki M, Kolcic I, Kovacs P, Kumari M, Kuusisto J, Kyvik KO, Laakso M, Lakka T, Lannfelt L, Lathrop GM, Launer LJ, Leander K, Li G, Lind L, Lindstrom J, Lobbens S, Loos RJ, Luan J, Lyssenko V, Mägi R, Magnusson PK, Marmot M, Meneton P, Mohlke KL, Mooser V, Morken MA, Miljkovic I, Narisu N, O’Connell J, Ong KK, Oostra BA, Palmer LJ, Palotie A, Pankow JS, Peden JF, Pedersen NL, Pehlic M, Peltonen L, Penninx B, Pericic M, Perola M, Perusse L, Peyser PA, Polasek O, Pramstaller PP, Province MA, Räikkönen K, Rauramaa R, Rehnberg E, Rice K, Rotter JI, Rudan I, Ruokonen A, Saaristo T, Sabater-Lleal M, Salomaa V, Savage DB, Saxena R, Schwarz P, Seedorf U, Sennblad B, Serrano-Rios M, Shuldiner AR, Sijbrands EJ, Siscovick DS, Smit JH, Small KS, Smith NL, Smith AV, Stančáková A, Stirrups K, Stumvoll M, Sun YV, Swift AJ, Tönjes A, Tuomilehto J, Trompet S, Uitterlinden AG, Uusitupa M, Vikström M, Vitart V, Vohl MC, Voight BF, Vollenweider P, Waeber G, Waterworth DM, Watkins H, Wheeler E, Widen E, Wild SH, Willems SM, Willemsen G, Wilson JF, Witteman JC, Wright AF, Yaghootkar H, Zelenika D, Zemunik T, Zgaga L; DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; The Multiple Tissue Human Expression Resource (MUTHER) Consortium, Wareham NJ, McCarthy MI, Barroso I, Watanabe RM, Florez JC, Dupuis J, Meigs JB, Langenberg C. A genome-wide approach accounting for body mass index identifies ge-netic variants influencing fasting glycemic traits and insulin resistance. Nature Genetics. 2012 June;44(6):659-669.

Methé BA, Nelson KE, Pop M, Creasy HH, Giglio MG, Huttenhower C, Gevers D, Petrosino JF, Abubucker S, Badger JH, Chinwalla AT, Earl AM, FitzGerald MG, Fulton RS, Hallsworth-Pepin K, Lobos EA, Madupu R, Magrini V, Martin JC, Mitreva M, Muzny DM, Sodergren EJ, Versalovic J, Wollam AM, Worley KC, Wortman JR, Young SK, Zeng Q, Aagaard KM, Abolude OO, Allen-Vercoe E, Alm EJ, Alvarado L, Andersen GL, Anderson S, Appelbaum E, Arachchi HM, Armitage G, Arze CA, Ayvaz T, Baker CC, Begg L, Belachew T, Bhonagiri V, Bihan M, Blaser MJ, Bloom T, Bonazzi VR, Brooks P, Buck GA, Buhay CJ, Busam DA, Campbell JL, Canon SR, Cantarel BL, Chain PS, Chen IM, Chen L, Chhibba S, Chu K, Ciulla DM, Clemente JC, Clifton SW, Conlan S, Crabtree J, Cutting MA, Davidovics NJ, Davis CC, DeSantis TZ, Deal C, Delehaunty KD, Dewhirst FE, Deych E, Ding Y, Dooling DJ, Dugan SP, Dunne W Jr, Durkin A, Edgar RC, Erlich RL, Farmer CN, Farrell RM, Faust K, Feldgarden M, Felix VM, Fisher S, Fodor AA, Forney L, Foster L, Di Francesco V, Friedman J, Friedrich DC, Fronick CC, Fulton LL, Gao H, Garcia N, Giannoukos G, Giblin C, Giovanni MY,

High Impact Research, continued from pg. 9

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Goldberg JM, Goll J, Gonzalez A, Griggs A, Gujja S, Haas BJ, Hamilton HA, Harris EL, Hepburn TA, Herter B, Hoffmann DE, Holder ME, Howarth C, Huang KH, Huse SM, Izard J, Jansson JK, Jiang H, Jordan C, Joshi V, Katancik JA, Keitel WA, Kelley ST, Kells C, Kinder-Haake S, King NB, Knight R, Knights D, Kong HH, Koren O, Koren S, Kota KC, Kovar CL, Kyrpides NC, La Rosa PS, Lee SL, Lemon KP, Lennon N, Lewis CM, Lewis L, Ley RE, Li K, Liolios K, Liu B, Liu Y, Lo CC, Lozupone CA, Lunsford R, Madden T, Mahurkar AA, Mannon PJ, Mardis ER, Markowitz VM, Mavrommatis K, McCorrison JM, McDonald D, McEwen J, McGuire AL, McInnes P, Mehta T, Mihindukulasuriya KA, Miller JR, Minx PJ, Newsham I, Nusbaum C, O’Laughlin M, Orvis J, Pagani I, Palaniappan K, Patel SM, Pearson M, Peterson J, Podar M, Pohl C, Pollard KS, Priest ME, Proctor LM, Qin X, Raes J, Ravel J, Reid JG, Rho M, Rhodes R, Riehle KP, Rivera MC, Rodriguez-Mueller B, Rogers YH, Ross MC, Russ C, Sanka RK, Sankar P, Sathirapongsasuti J, Schloss JA, Schloss PD, Schmidt TM, Scholz M, Schriml L, Schubert AM, Segata N, Segre JA, Shannon WD, Sharp RR, Sharpton TJ, Shenoy N, Sheth NU, Simone GA, Singh I, Smillie CS, Sobel JD, Sommer DD, Spicer P, Sutton GG, Sykes SM, Tabbaa DG, Thiagarajan M, Tomlinson CM, Torralba M, Treangen TJ, Truty RM, Vishnivetskaya TA, Walker J, Wang L, Wang Z, Ward DV, Warren W, Watson MA, Wellington C, Wetterstrand KA, White JR, Wilczek-Boney K, Wu YQ, Wylie KM, Wylie T, Yandava C, Ye L, Ye Y, Yooseph S, Youmans BP, Zhang L, Zhou Y, Zhu Y, Zoloth L, Zucker JD, Birren BW, Gibbs RA, Highlander SK, Weinstock GM, Wilson RK, White O. A framework for human microbiome research. Nature. 2012 Jun 13;486(7402):215-21.

Mohr DC, Ho J, Duffecy J, Reifler D, Sokol L, Burns MN, Jin L, Siddique J. Effect of telephone-administered vs face-to-face cognitive behavioral therapy on adherence to therapy and depression outcomes among primary care patients: a randomized trial. JAMA- Journal of the American Medical Association. 2012 Jun 6;307(21):2278-85.

Radulovic J, Tronson NC. Preso1, mGluR5 and the machinery of pain. Nature Neuroscience. 2012 May 25;15(6):805-7.

Serebrennikova OB, Tsatsanis C, Mao C, Gounaris E, Ren W, Siracusa LD, Eliopoulos AG, Khazaie K, Tsichlis PN. Tpl2 abla-tion promotes intestinal inflammation and tumorigenesis in Apcmin mice by inhibiting IL-10 secretion and regulatory T-cell generation. Proceedings of the National Academy of Sciences U S A. 2012 May 1;109(18):E1082-91.

Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, Solomon JA, Yoo S, Arron ST, Friedlander PA, Marmur E, Rudin CM, Chang AL, Low JA, Mackey HM, Yauch RL, Graham RA, Reddy JC, Hauschild A. Efficacy and safety of vismo-degib in advanced basal-cell carcinoma. New England Journal of Medicine. 2012 Jun 7;366(23):2171-9.

Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN. Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature. 2012 May 13;485(7400):599-604.

Srivastava DP, Woolfrey KM, Jones KA, Anderson CT, Smith KR, Russell TA, Lee H, Yasvoina MV, Wokosin DL, Ozdinler PH, Shepherd GM, Penzes P. An autism-associated variant of epac2 reveals a role for ras/epac2 signaling in controlling Basal dendrite maintenance in mice. PLoS Biology. 2012 Jun;10(6):e1001350.

High Impact Research, continued from pg. 10

Help Feinberg Track JournalsThe Feinberg Research Office regularly tracks research published by Feinberg investigators. The citations are used on web pages, in newsletters and social media, for internal reporting, and more. To more accurately track these journals, the Research Office asks that Feinberg investigators use the following institution name in the address field when pub-lishing in peer-reviewed journals: “Northwestern University Feinberg School of Medicine.”

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Funding OpportunitiesSpecialized Programs of Research Excellence (SPOREs) in Human Cancer for Years 2010, 2011 and 2012 (P50)More information

Sponsors: Department of Health and Human Services (HHS), National Institutes of Health (NIH) Submission Deadline: September 20 (LOI August 20) Upper Amount: $12.5 million

Synopsis: The National Cancer Institute (NCI), the National Institute of Dental and Craniofacial Research (NIDCR), and the National Institute of Neurological Dis-orders and Stroke (NINDS) invite new or renewal (com-peting) applications for P50 Research Center Grants for Specialized Programs of Research Excellence (SPOREs). The program will fund five-year P50 SPORE grants to support state-of-the-art investigator-initiated research that will contribute to improved detection, diagnosis, treatment, and prevention of an organ-specific cancer (or a related group of cancers). SPOREs are expected not only to conduct a wide spectrum of research activities, but also to contribute significantly to the development of specialized research COREs, improved research model systems, and collaborative research projects with other institutions. The research supported through this program must be translational in nature and must be based upon knowledge of human biology stemming from research us-ing cellular, molecular, structural, biochemical, or genetic experimental approaches.

Translational Programs in Lung Diseases (P01) More information

Sponsor: United States Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI) Submission Deadline: September 26 (LOI August 26) Upper Amount: $8.75 million

Synopsis: This opportunity solicits Program Project Grant (P01) applications from institutions and organizations that will perform collaborative, translational research that moves mechanistic research to clinical applications to improve prevention, diagnosis, or treatment of lung diseases and sleep disorders.

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3rd Annual Prostate Cancer Public Education Forum This is a free forum intended for patients, spouses, advocates, and healthcare professionals.Date: Saturday, September 8, 8 a.m. to 3 p.m.Location: Lurie Research Center — Hughes 303 E. Superior St. (Chicago campus)Contact: cancer@northwestern.edu More information

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8/13 Myron & Muriel S. Bender Distinguished Lecture Series in Organic Chemistry Presented by Tom W. Muir, PhD, Princeton UniversityDate: Monday, August 13, 4 to 5 p.m. Lecture: “Protein ligation: Organic chemistry on big proteins”

Location: Technological Institute – Tech L211 2145 Sheridan Road (Evanston campus)

Date: Tuesday, August 14, 4 to 5 p.m.Lecture: “Chromatin: An expansive canvas for chemical biology”Location: Technological Institute – Tech L211 2145 Sheridan Road (Evanston campus)

Date: Wednesday, August 15, 11 a.m. to noon Lecture: “When bugs talk: Virulence regulation in Staphylococci”Location: Ryan Hall 4003 2190 Campus Drive (Evanston campus)

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Pediatric Grand Rounds “Guidelines for management of severe pediat-ric traumatic brain injury: progress, pitfalls and a dearth of data,” presented by Mark Wainright, MD, PhD, FeinbergDate: Friday, August 17, 8 to 9 a.m.Location: Lurie Children’s Hospital 11th Floor Conference Center 225 E. Chicago Ave. (Chicago campus)Contact: BVonRueden@luriechildrens.org More information

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