The Ohio State University Medical Center 2009 Research Report

Advancing Personalized Health Care The Ohio State University Medical Center

2009 Research Report

2009 Research Report

Greetings…

Even as recently as our own medical school training, we could not have imagined that surgeries would someday be performed using robotics, that for many, many patients heart disease, cancer and HIV/AIDS would become chronic health conditions instead of the rapid killers they once were, or that a person’s genetic makeup would be a factor in planning their health future or selecting one therapy over another.

Yet, these are all standards of medical practice today, all made possible by biomedical research at The Ohio State University Medical Center and at other academic medical centers throughout the world.

This 2009 Research Report documents another year in Ohio State’s rapid growth into one of the largest research powerhouses in the nation. Our size and single-site location are together one of our greatest strengths. We have more health sciences colleges located in close proximity to one another than any other U.S. university, and our success in obtaining NIH and other grants has advanced the construction of extensive laboratory and clinical infrastructure. The National Science Foundation ranks Ohio State 10th in total research expenditures (including the health sciences) among public and private universities, seventh among public universities, and second in industry-sponsored research.

Fundamental to this progress is having a large and talented team of faculty and staff dedicated to excellence and collaboration.

This creates tremendous opportunity for making discoveries that translate directly into better health care for all.

We are embarking on one of the largest medical construction and renovation projects in the nation this year. We’re calling it ProjectONE and, over the next six years, this $1 billion project will include the construction of a new cancer hospital, critical care facility and interconnected designated areas for research, teaching, collaboration and reflection. This new facility is designed to promote personalized health care – the healthcare model of the future, which is personalized, predictive, preventive and participatory, based on each patient’s unique biology, behavior and environment.

We encourage you to follow our progress at www.medicalcenter.osu.edu.

Meanwhile, we can only imagine the advances that biomedical research will bring over the next 20 years. You can be assured, however, that Ohio State faculty and staff will focus on ”creating the future of medicine to improve people’s lives through personalized health care.”

Sincerely,

Steven G. Gabbe, MD Wiley W. ”Chip” Souba, MD, ScD Clay B. Marsh, MD Senior Vice President for Health Sciences, Vice President and Executive Dean Senior Associate Vice President for The Ohio State University for Health Sciences Health Sciences Research, OSU Medical Center Chief Executive Officer, Dean, College of Medicine Vice Dean of Research, OSU College of Medicine The Ohio State University Medical Center Executive Director, OSU Center

for Personalized Health Care

The Ohio State University Medical Center

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2009 Research Report

Achieving Personalized Health Care through Collaborative Research

Through research, we are discovering that the key to understanding disease does not rest in the information found within a single cell, but rather in multiple changes found within a larger environment, and that the symptoms of disease are often the end result of a chain of smaller events throughout the body.

We are discovering that the key to treating disease does not rest simply in a surgical procedure or medication; that good health relies on more than physiological well being. The ability for patients to properly manage stress and maintain a positive mindset before and after their treatment can have a significant impact on the success of treatment or the progression of disease.

Discoveries like these are ushering in a new era of personalized health care, of treatments as unique as each person who needs them. But, in order to move these discoveries into the clinical realm, scientists need the ability to communicate and collaborate across disciplines, to have access to resources and facilities that will help them distill their knowledge into tools that can advance patient care and improve people’s lives.

The Ohio State University Medical Center

The Ohio State University Medical Center provides an ideal atmosphere for translational research. Collaboration is in our DNA, evident in everything from our standing as one of the most comprehensive health sciences campuses in the United States, to our focus on open labs and shared services that promote work across disciplines and efficient use of research funding, to the construction of biomedical informatics data banks that help us share our discoveries across the University and the world. And, with the May 2008 awarding of a $34 million Clinical and Translational Science Award from the National Institutes of Health, Ohio State is positioned to be at the epicenter of future medical breakthroughs.

With this report, we share both a year of successes in basic, translational and clinical research and the steps we’ve taken to secure and enrich the unique collaborative atmosphere of The Ohio State University Medical Center.

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The Ohio State University Medical Center’s

NOTABLE discoveries of 2008 First Patients Enrolled in Worldwide Heart Therapy Trial A central Ohio man and woman became the first in the world to receive a heart implant in a U.S. Food and Drug Administration-approved study to determine how cardiac resynchronization therapy (CRT) affects certain heart-failure patients who are currently not considered for this treatment.

Doctors implant an EchoCRT that allows the heart chambers to work in sync, potentially increasing the heart’s efficiency and strengthening heart muscle. The device can be implanted without general anesthesia or open-heart surgery.

“We are focused on improving the survival rate for heart-failure patients and reducing the hospitalization rate for worsening heart failure,” says William Abraham, MD, national principal investigator for the trial.

The implants were performed at Ohio State’s Richard M. Ross Heart Hospital. Signature Program: Heart (p.14)

Molecular Change May Reveal Risk of Leukemia Relapse Researchers at Ohio State’s Comprehensive Cancer Center may have discovered a better way to distinguish acute leukemia patients who require aggressive treatment to prevent recurrence from those who need only standard therapy for cure. In a study published in the New England Journal of Medicine, researchers say changes in levels of microRNAs – tiny molecules used by cells to help control the kinds and amounts of proteins they make – might predict the risk of relapse in many adults diagnosed with acute myeloid leukemia (AML).

Study leader Clara D. Bloomfield, MD, says the findings, if validated in a large prospective study, could help predict individual patient outcomes, identify the most effective therapy and lead to new targeted therapies. Signature Program: Cancer (p.12)

Identifying Cell Processes that Regulate Wound Healing Scientists at Ohio State uncovered cell processes that will open new therapeutic approaches to wound healing.

The findings were the first to prove that redox signaling – a process that produces oxygen derivatives that act as messengers in biological systems – is regulated by microRNA. Specifically, the research showed that microRNA can be regulated in certain blood vessel cells, influencing their ability to make the vessels regenerate tissue needed in wound healing.

The research, led by Chandan Sen, PhD, director of Ohio State’s Comprehensive Wound Center, was published in the journal Arteriosclerosis, Thrombosis and Vascular Biology.

Signature Programs: Critical Care (p.13); Heart (p.14)

Molecule Linked to Muscle Cancer Researchers at Ohio State’s Comprehensive Cancer Center have discovered that a molecule implicated in leukemia and lung cancer is also important in muscle repair and in a muscle cancer that strikes mainly children.

The study shows that immature muscle cells require a type of microRNA, called miR-29, to become mature, and that the molecule is nearly missing in cells from rhabdomyosarcoma, a cancer caused by the proliferation of immature muscle cells. Cells from human rhabdomyosarcoma tumors showed levels of the molecule that were 10 percent or less of those in normal muscle cells. Artificially raising the level of the molecule in the cancer cells cut their growth by half and caused them to begin maturing, slowing tumor growth.

The study, led by Denis Guttridge, PhD, was published in the journal Cancer Cell. Signature Program: Cancer (p.12)

The Ohio State University Medical Center

Chandan Sen, PhD

Exploring Additional Benefits of Aspirin For decades, physicians have been prescribing aspirin for patients experiencing heart attack symptoms or as a preventive measure for those at high risk for cardiovascular disease. A study at Ohio State’s Medical Center indicated that aspirin may also increase the amount and quality of high-density lipoprotein (HDL) the body produces.

This study was published in the Journal of Lipid Research.

“We were able to show that aspirin might induce production of the protein components of HDL, which takes cholesterol out of the plaque and moves it back to the liver where it can be utilized,” says Sampath Parthasarathy, PhD, director of research in the Division of Cardiothoracic Surgery.

“While aspirin has been used for its anti-inflammatory properties, we hope to create a new level of interest in its other potential benefits.” Signature Program: Heart (p.14)

Colon Cancer Linked to Unequal Gene Activity Researchers at Ohio State’s Comprehensive Cancer Center discovered that a difference in the activity of a pair of genes may be responsible for one of every 10 colon cancer cases.

The study, published in the journal Science, was the first to link the gene conclusively as a cause of colon cancer, and it may give clinicians a new way to identify people at high risk for the disease.

The gene is called transforming growth factor beta receptor 1 (TGFBR1). Everyone inherits two copies of it, and both usually produce equal amounts of the RNA needed

to make the TGFBR1 protein. But, in some people, one of these two genes produces less than the other. “That we saw this abnormal difference in at least 10 percent of the colon cancer patients and in very few people without colon cancer strongly suggests that it plays a role in this disease,” says principal investigator Albert de la Chapelle, MD, PhD, of the Center’s Molecular Biology and Cancer Genetics Program.

Signature Program: Cancer (p.12)

Intervention Program Boosts Survival in Breast Cancer Patients An Ohio State study provided the best evidence yet that a psychological intervention program designed for breast cancer patients improves their health and increases their chance of survival. “By teaching patients strategies to reduce stress, improve mood and alter health behaviors, we found that their risk of dying from breast cancer was reduced by 56 percent after an average of 11 years,” says Barbara Andersen, PhD, lead author of a study published in the journal Cancer.

“We have empirically documented that stress reduction is good for patients’ mental health and also may improve their physical health.” Signature Program: Cancer (p.12)

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NOTABLE DISCOVERIES (continued)

Novel Blood Test Detects Ovarian Cancer A pilot study by researchers at Ohio State’s Comprehensive Cancer Center found that a novel blood test that screens for microRNAs can reliably detect ovarian cancer, even among patients who test negative for the disease with the widely used CA-125 blood test.

“Too many women die from ovarian cancer because it often is detected too late,” says David Cohn, MD, a gynecologic surgical oncologist and researcher. “We are trying to use a blood test to detect it earlier, when the prognosis is better. We can clearly define the microRNA pattern in the blood of patients with this disease; these findings could have implications for other cancers as well.”

The findings were published in the journal Gynecologic Oncology. Signature Program: Cancer (p.12)

animals that consumed freeze-dried black raspberry powder during the exposure.

The findings, published in the journal Cancer Research, also helped identify 53 genes that may play a fundamental role in early cancer development. “We have shown that berries, which contain a variety of anticancer compounds, have a genome-wide effect on the expression of genes involved in cancer development,” Stoner says. Signature Program: Cancer (p.12)

Exposure to Bad Air Increases Hypertension Cardiovascular researchers at Ohio State became the first to report a direct link between air pollution and its impact on high blood pressure. If results from these animal studies hold up, they could have important implications for human health.

“We now have even more compelling evidence of the strong relationship between air pollution and cardiovascular disease,” says Sanjay Rajagopalan, MD, co-author of the most recent study, which builds on previous research that his team published in the journals Circulation, Inhalation and the Journal of the American Medical Association.

The results of the latest study, published in the journal Arteriosclerosis, Thrombosis and Vascular Biology, found that short-term exposure to air pollution over a 10-week period elevated blood pressure in those already predisposed to the condition. Signature Program: Heart (p.14)

Black Raspberries Slow Cancer by Altering Genes Research at Ohio State’s Comprehensive Cancer Center (OSUCCC) suggested that a mix of preventive agents, such as those found in concentrated black raspberries, may more effectively inhibit cancer development than single agents aimed at shutting down a particular gene.

Investigators led by Gary Stoner, PhD, of the OSUCCC’s Molecular Carcinogenesis and Chemoprevention Program, examined the effect of freeze-dried black raspberries on genes altered by a chemical carcinogen in an animal model of esophageal cancer. The carcinogen affected the activity of some 2,200 genes in the animals’ esophagus in only a week, but 460 of those genes were restored to normal activity in

Mini Regulatory Molecules Found in Circulating Blood Researchers at Ohio State identified for the first time microRNAs in the circulating blood of healthy human volunteers.

A study published in Public Library of Science (PloS One) found the mini-regulatory molecules inside tiny sacs, or microvesicles, circulating in the bloodstream. Their function isn’t yet known, but principal investigator Clay Marsh, MD, says their discovery there is the first step in determining their role in the blood and whether they might be used to predict the presence of disease.

“These microRNAs and microvesicles flowing in the blood may be a system used by our bodies to communicate between distant organ sites,” says Marsh. “Our findings strongly suggest that they are actively packaged and processed by cells.”

Altered microRNA levels are associated with a variety of diseases, including cancer. The researchers also speculate that microRNAs may control production of bone marrow cells.

Signature Programs: Critical Care (p.13); Cancer (p.12)

Potential Link Found Between Sleep Apnea, Heart Disease Sleep medicine and cardiovascular experts at Ohio State discovered a possible link between sleep apnea and heart disease.

The researchers wanted to see what would happen to fat cell secretion of certain substances when sleep apnea was simulated. While most substances secreted by fat cells have

The Ohio State University Medical Center

undesirable effects, others, such as adiponectin, may have beneficial effects and even prevent artherosclerosis. The findings, published in the journal Experimental and Clinical Endocrinology & Diabetes, showed that when fat cells were exposed to repetitive dipping of oxygen levels, similar to that found in patients with sleep apnea, the secretion of adiponectin decreased.

“Since adiponectin appears to prevent artherosclerosis, this could explain why patients with obstructive sleep apnea are predisposed to develop heart disease,” says principal investigator Ulysses Magalang, MD. Signature Programs: Critical Care (p.13); Heart (p.14)

Critical Care Doctors Use Strength Test to Predict Outcomes A multicenter study led by Ohio State showed that using a simple bedside handgrip test may help diagnose a complication of critical illness often associated with an increased risk of death.

Researchers used handgrip tests to gauge the strength of critically ill patients in intensive care units at five academic medical centers. The patients were on a ventilator for at least five days and had no evidence of pre-existing neuromuscular disease. Researchers found that handgrip strength was lower in patients with intensive care unit-acquired weakness and that those patients had good test performance for diagnosis.

These patients also had longer hospital stays and required a ventilator for a longer time.

“Handgrip strength is also independently associated with poor hospital outcomes and may serve as a simple test that can readily identify weakness,” says study leader Naeem Ali, PhD. The study was published in the American Journal of Respiratory and Critical Care Medicine. Signature Program: Critical Care (p.13)

Location Important for Genes To better understand how cells become cancerous after losing control of their growth, scientists at Ohio State’s Comprehensive Cancer Center examined four genes that help regulate cell growth in embryos and contribute to cancer in adults.

The genes – E2f1, E2f2, E2f3a and E2f3b – are generally believed to work together to help control cell proliferation, based on experiments using only cells. But researchers led

by Gustavo Leone, PhD, carried out several studies in an animal model to learn if it is also true in the body during development. The scientists also hoped to learn why many organisms, including humans, have multiple E2F genes of this type, while other animals have just one copy.

“We found that if E2f3a is present, the animals can develop normally through adulthood, even when all the other genes are absent,” says Leone.

The study was published in the journal Nature. Signature Program: Cancer (p.12)

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A blueprint for collaboration: Ohio State’s Center for Clinical and Translational Science

“One of our main drives is rethinking our social responsibility and translating our greatest ideas from basic science discovery to better clinical practices in a collaborative fashion,” says Rebecca Jackson, MD, associate dean for clinical research in Ohio States’ College of Medicine, of the exploratory spirit that propels the dedicated basic, clinical and translational researchers working within Ohio State’s Medical Center.

It was this drive for discovery that helped The Ohio State University Medical Center land a $34.1 million Clinical and Translational Science Award (CTSA) from the National Institutes of Health. The award places the Medical Center in a national consortium of elite institutions charged with the same mission: to improve health care by creating a clinical and translational science discipline that brings new treatments to patients more efficiently and quickly.

The Ohio State University, in partnership with Nationwide Children’s Hospital (NCH), has developed the Center for Clinical and Translational Science (CCTS) to help achieve this mission, and Jackson, principal investigator for the CCTS, says that important strides made in the development of the Center have encouraged and engaged faculty, students and staff alike.

In its first year alone, the CCTS has redefined the traditional boundaries of clinical and translational research, demonstrating its importance not only to the colleges of Medicine and Public Health, but also in fostering collaboration among other University research areas. To date, CCTS resources have been utilized by faculty, students and trainees from nine Ohio State University colleges and NCH, representing more than 65 areas of expertise. Faculty and students from three additional colleges have participated in one or more CCTSsponsored activities, such as workflow-analysis, educational programming or the development of the CCTS Web portal.

Graduate students from the Department of Industrial,

Rebecca Jackson, MD

Interior and Visual Communication Design in the College of the Arts designed the CCTS public Web portal. The College uses the site as a laboratory to analyze strategies for disseminating scientific information and developing teams.

It is the well-crafted organizational infrastructure of the CCTS that has made possible the wide use of CTSA and institutional resources in clinical and translational research.

The Center is fully prepared to support Ohio State’s highperformance research culture. This administrative core also enables the CCTS to advocate for the needs of the research community with senior University officials.

The CCTS has created research training programs that enable teams to pursue pressing issues in translational science. The CCTS supported the development of interdisciplinary teams, including efforts in drug discovery and target validation in infectious disease, where expertise and experimental methods from the colleges of Medicine, Pharmacy, Public Health, Agriculture and Veterinary Medicine came together to address a global health issue.

The CCTS has offered its resources and funds to help several clinical and translational researchers, granting 10 trainee and six junior faculty scholar awards.

In addition, the CCTS has transformed three degreegranting programs to support its education and careerdevelopment mission. This includes developing a new PhD in Implementation Science that focuses on practice-based research skills.

The Ohio State University Medical Center

One of the most successful ways that CCTS resources have driven innovation and team science is through pilot funding. The Center issued six pilot-funding application requests and received more than 150 submissions. Senior scientists in the CCTS will mentor the new teams funded by the pilot studies program.

The CCTS also has progressed toward greater community engagement at the medical, University and community levels. This expanded engagement has integrated childhealth investigators and trainees from Nationwide Children’s Hospital in every aspect of CCTS programming. NCH faculty play lead roles as co-principal investigators or co-leads for the Regulatory, Participant and Clinical Interactions Resources and Community Engagement programs.

Due to a lack of awareness and interest in the clinical and translational sciences among younger audiences, the CCTS is striving to increase community and student involvement by including future students who are interested in these disciplines. The Community Engagement program has worked with the Clinical Research Center to create a half-day experimental field trip for middle school students wishing to learn about clinical research.

Jackson hopes CCTS research continues to promote “community engagement [that can] actually bring [researchers] back into the clinical setting or out into the community so that practitioners, consumers and others can use the best information to make their own healthcare decisions.”

In what has been a highly successful and eventful first year, the CCTS has expanded the University’s interdisciplinary translational focus to include representation from colleges across the academic spectrum. By developing a forum to share curriculum, address the early stages of career development, and promote retention, Ohio State’s Center for Clinical and Translational Science hopes to cultivate collaboration across the entire Ohio State community.

CCTS Programs: Biomedical Informatics Community Engagement Design, Biostatistics and Ethics Support and Training Novel Clinical and Translational Methodologies Participant and Clinical Interactions Resources Pilot and Collaborative Translational and Clinical Studies Regulatory Knowledge and Support Research Education, Training and Career Development Tracking and Evaluation Translational Technologies and Core Resources

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Featured programs

As both discoveries in the lab and the delivery of medicine continue to shift toward personalized health care, we have selected these three areas of research as “featured programs” for their significant accomplishments in 2008.

Personalized Health Care PHC is the use of genetic, environmental and behavioral information to determine each patient’s unique disease prevention needs and individually tailored medical therapies. Ohio State created the Center for Personalized Health Care (CPHC) in 2005 to incorporate PHC initiatives into clinical care, research and training programs and to advance PHC globally. Clay Marsh, MD, was named CPHC director in June 2009. This year, the CPHC has: • Led an initiative to devise a patient informed-consent process to accelerate the development of a centralized biorepository for personalized medicine research.

• Developed and implemented a grant program to support PHC research at Ohio State. The first grant went to an AASK ACE1 clinical genotyping study.

• Evaluated and validated genomic/genetic biomarker tests, such as the Warfarin DNA sensitivity test, for clinical use at Ohio State.

Women’s Health Women’s health research at Ohio State examines the role gender plays in disease, specifically in diseases that disproportionately affect women biologically, psychosocially or behaviorally. Exploring these variables across the lifespan is a fundamental goal of research in Ohio State’s Center for

Women’s Health (CWH), led by Rebecca Jackson, MD. This year, the CWH has: • Renewed NIH funding for efforts to determine genetic associations for hip fracture (Rebecca Jackson, MD).

• Studied microRNA patterns and exhaled gases to determine the role they play in premenstrual asthma (Jennifer McCallister, MD).

• Examined the role of iron balance in the development and progression of atherosclerosis in perimenopausal women.

(Subha Raman, MD).

Perinatal Research Ohio State’s Maternal Fetal Medicine (MFM) program is a national leader in perinatology care. It is similarly renowned for its basic and clinical research in preterm birth, diabetes in pregnancy and the in utero treatment of fetal disease. The Laboratory of Perinatal Research (LPR), led by Douglas Kniss, PhD, was established in 1988. This year, the LPR: • Explored the causal connections between inflammation and preterm birth (Douglas Kniss, PhD, and William Ackerman, PhD).

• Used nanotechnology to model topography and geometry in tissue development for potential application in tissue engineering and regeneration (collaboration with John Lannutti, PhD, of Ohio State’s College of Engineering).

• Completed its 16th year of participation in the 14-center Maternal-Fetal Medicine Units (MFMU) Network, whose landmark clinical trial on treating mild gestational diabetes mellitus has shown the benefits of treating mild carbohydrate intolerance during pregnancy (Jay Iams, MD, and Mark Landon, MD).

The Ohio State University Medical Center

Ohio State University Medical Center’s

Signature Programs

To optimize the resources and strengths of the Medical Center in our pursuit of distinction in research, education and patient care, Ohio State has identified six specialties as Signature Programs – Cancer, Critical Care, Heart, Imaging, Neurosciences and Transplantation. These programs are characterized by demonstrated leadership, national reputation and potential for growth.

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Michael A. Caligiuri, MD

Cancer Led by Michael A. Caligiuri, MD, the Cancer Signature Program is embodied in The Ohio State University Comprehensive Cancer Center (OSUCCC), one of only 40 National Cancer Institute (NCI)-designated comprehensive cancer centers in the nation. The OSUCCC is a network of six interdisciplinary, cancer-related research programs that collectively comprise more than 250 investigators whose work encompasses the entire cancer continuum – from identifying biological causes of the disease to applying these discoveries to innovative strategies in prevention, diagnosis, treatment and survivorship.

The patient-care component of the OSUCCC is the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

• The OSUCCC-James enrolled 1,025 patients onto therapeutic trials, a single-year record for Ohio State. In August 2009, the OSUCCC–James achieved ahead of schedule the goal for its “2010 by 2010” campaign, an initiative launched in November 2007 that sought to enroll 2,010 patients onto therapeutic clinical trials by March 2010. By the end of September 2009, the campaign had accrued 2,129 patients.

• The NCI awarded the OSUCCC a five-year, $3.8 million grant for conducting phase I clinical trials to assess toxicity and safe dosage levels of promising anticancer agents.

• Ohio State is one of only 14 institutions selected by the NCI to receive a grant contract specifically for conducting phase I studies, and one of only five in the nation to hold NCI contracts for conducting both phase I and phase II clinical trials on new anticancer agents.

Cancer Program Steering Committee: Clara D. Bloomfield, MD John Byrd, MD Michael A. Caligiuri, MD William Carson III, MD Scott Jewell, PhD Michael Lairmore, DVM, PhD Electra Paskett, PhD

Cancer Signature Program highlights of 2008 • The OSUCCC maintained $38 million in National Cancer Institute (NCI)-funding for cancer research, ranking 16th among all NCI-funded institutions for the year.

When Derrick Dozier discovered he had prostate cancer, the options available to him would give anyone information overload. At Ohio State, The James brings experts from all specialties together in a single clinic, developing personalized treatment plans for each patient. Derrick chose robotic prostatectomy and is back on the links. Learn more at http://medicalcenter.osu.edu/go/phcstories

The Ohio State University Medical Center

Critical Care

Clay Marsh, MD

Under the leadership of Clay Marsh, MD, Ohio State’s Critical Care Signature Program includes the Medical Intensive Care Unit, Surgical Intensive Care Unit, University Hospital East ICU, Cardiac ICU at the Ross Heart Hospital, Blood and Marrow Transplant at the OSUCCC-James, Ohio State’s Burn Center, Level 1 Trauma Center, Comprehensive Wound Center and Respiratory program. By tracking patient outcomes and studying the molecular networks that determine patient outcomes, the program hopes to change current practice from disease management to prediction and prevention of disease.

Critical Care Signature Program highlights of 2008 • The Center for Critical Care saw strong growth in clinical research, conducting 52 active clinical trials that enrolled more than 500 people in 2008 and 2,500 over the past five years.

• The Center renewed a T32 training grant in pulmonary medicine and had eight new investigators funded by external agencies, including NIH, American Thoracic Society and Flight Attendant Medical Research Institute.

Overall research funding exceeded $12 million.

• The Center is planning its first MATCH (Multidisciplinary Advances in the Treatment of the Critically ill Hospitalized patient) conference, an event focused on evidence-based practices in treating patients with critical care disease.

• The Center for Critical Care improved focus on safety and quality and realized a 50-percent reduction in ventilatorassociated pneumonia.

• Ohio State’s Burn Program achieved Burn Center verification by the American Burn Association, and the Trauma Program achieved re-verification as a Level 1 Trauma Center.

• The Center trained 146 individuals through systematic application of the Society of Critical Care Medicine’s Fundamentals of Critical Care Support Course.

Critical Care Program Steering Committee: Lori Abshire Stephen Hoffmann, MD Naeem Ali, MD David Lindsey, MD Larry Anstine Clay Marsh, MD Jessica Backer Armin Rahmanian Charles Cook, MD Thomas Reilley, MD Elliott Crouser, MD Chandan Sen, PhD Leroy Essig, MD Beth Steinberg, RN Molly Fontana Henry Zheng, PhD, MBA Terri Gillenwater

Charlie Billingsley, Ohio State varsity lacrosse player, would get tightness in his chest that kept him from playing as hard as he wanted Researchers at Ohio State discovered he had exercise-induced asthma, common among competitive athletes.

Now, through personalized education and treatment, Charlie’s back on the field. Learn more at http://medicalcenter.osu.edu/go/phcstories

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Heart Translational research occurs across all aspects of the Heart Signature Program, led by Thomas Ryan, MD. Areas of study include heart failure, ischemic disease, transplantation, arrhythmias/electrophysiology and vascular disease.

Patient care is provided at the Richard M. Ross Heart Hospital, University Hospital, University Hospital East, and at local and regional outpatient clinics associated with Ohio State. Educational opportunities within the program include fellowship training in cardiovascular medicine, cardiac surgery and vascular surgery, along with doctoral, postdoctoral and continuing medical education programs.

Heart Signature Program highlights of 2008 • Scientists in this program maintained $19.63 million in research funding and were involved with 141 active clinical trials.

• The program received NIH funding to research mechanisms by which aspirin might protect against atherosclerosis.

• Recent bioinformatic annotation has established that human chromosome 21 harbors five microRNA genes that are overexpressed in heart samples from individuals with Down syndrome, which may contribute to congenital heart defects in Down syndrome infants.

• Researchers continue to delineate mechanisms responsible for abnormal calcium handling in hereditary cardiac diseases and in acquired conditions such as heart failure and postinfarction sudden cardiac death syndrome.

Thomas Ryan, MD

• Heart Program research continues to develop innovations in cardiovascular imaging that provide earlier detection, more accurate diagnosis and personalized treatment of heart and vascular disease – work that led to 17 peerreviewed publications in 2008.

Heart Program Steering Committee: Thomas Ryan, MD Benjamin Sun, MD William Abraham, MD Patrick Vaccaro, MD Jay Kasey Terry Elton, PhD Vanessa Moses Linda Paxton Charles Bush, MD Lorri Sayre-Fowler Randy Allen Periannan Kuppusamy, PhD

Joe Heskett was a likely candidate for the 2008 Olympic wrestling team when an undetected genetic heart disorder nearly ended his life. After examining his family history, doctors at Ohio State selected an implanted defibrillator and personalized heart care plan that keeps Joe in the wrestling game… coaching for Ohio State. Learn more at http://medicalcenter.osu.edu/go/phcstories

The Ohio State University Medical Center

Imaging Ohio State’s Department of Radiology has been a pacesetter in biomedical imaging research that translates to innovative clinical applications. The research backbone of the Imaging Signature Program, led by Michael Knopp, MD, PhD, is the Wright Center of Innovation in Biomedical Imaging.

The Center advances magnetic resonance imaging (MRI), positron emission tomography (PET) and mobile imaging technologies while creating an extensive imaging and bioinformatics structure. Transinstitutional efforts have involved the Ohio Supercomputer Center, Ohio State Computer Science and Engineering, and Ohio State’s College of Veterinary Medicine.

Imaging Signature Program highlights of 2008 • The Ohio Research Scholar program awarded more than $24.9 million to establish the Ohio Imaging Research and Innovation Network, which will build upon the Wright Center to establish a statewide cluster in imaging technology with 26 other academic and industrial organizations.

• Imaging progress was demonstrated in the use of a global positioning system (GPS) in the operating room and in MRI technologies that allow surgeons to make smaller scalp incisions and remove smaller segments of the skull during procedures.

• Imaging research activities included work describing new dimensions in the regulation of DNA damage processing; DNA repair protein trafficking in cells and targeting to

Michael Knopp, MD, PhD

damage in chromatin; and the role of protein ubiquitination and proteasomal degradation in transcription and genomic repair.

Imaging Program Steering Committee: Nate Hall, MD, PhD Kent Hess Michael Knopp, MD, PhD Adele Lipari, MD Rob McKenney, PhD Michael Tweedle, PhD Joseph Yu, MD William Yuh, MD

When a heart CT scan revealed a spot on her pancreas, llama breeder Donna Stephens thought she would need surgery to diagnose the problem.

But, through Ohio State’s use of endoscopic ultrasound, which offers evaluation, diagnosis and staging in a few hours, Donna discovered she required only periodic monitoring. No surgery. Learn more at http://medicalcenter.osu.edu/go/phcstories

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E. Antonio Chiocca, MD, PhD

Neurosciences Led by E. Antonio Chiocca, MD, PhD, the Neurosciences Signature Program involves multidisciplinary research in neurological surgery, neurology, neurosciences, molecular neurobiology, pharmacology, psychiatry, psychology, ENT (ear, nose and throat), the Center for Brain and Spine Injury, and the Center for Molecular Neurobiology. Clinical research occurs in the Cognitive Neuroscience Laboratory, the Dardinger Laboratory for Neuro-Oncology and Neuroscience Research, the departments of Neurology, Neurological Surgery, and Physical Medicine and Rehabilitation, and in the School of Allied Medical Professions. Basic research is conducted in the Neurobiology of Disease Institute, the Center for Molecular Neurobiology, the Department of Neuroscience, the Department of Pharmacology and in the Division of Neuropathology.

Neurosciences Signature Program highlights of 2008 • Researchers received a $5.5 million U01 grant from the National Institute of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) for a project titled “Preclinical Toxicity Evaluation of a Potent Oncolytic Virus.”

• Investigators received two NIH/NINDS contracts totaling $5 million to perform replication studies and training in traumatic spinal cord injury.

• The National Institute on Disability and Rehabilitation Research, U.S. Department of Education, awarded a fiveyear, $4.2 million grant for a project titled “Individualized Planning for the First Year Following Acute Rehabilitation.”

• The National Institute for Mental Health awarded program scientists a $1.5 million grant for a project titled “Photoperiod, Brain and Behavior.”

Neurosciences Program Steering Committee: Lori Abshire Melinda Akins David Bertsch Leigh Briggs E. Antonio Chiocca, MD, PhD Melanie Dheel James King, PhD William Pease, MD Wendy Pestrue Phillip Popovich, PhD Michael Racke, MD Radu Saveanu, MD Kyle Sharp Bradley Welling, MD, PhD Karen Wiles Anthony Young, PhD

Even though Tricia Smith moved to St. Louis, she still makes the seven-hour trip to Ohio State’s Multiple Sclerosis Center for her care. The Center considers each person’s health, medical history and tolerance for specific therapies in the development of personalized treatment plans, symptom management strategies and support. Learn more at http://medicalcenter.osu.edu/go/phcstories

The Ohio State University Medical Center

Michael Grever, MD

Transplantation The Transplantation Signature Program, led by Michael Grever, MD, coordinates the clinical care of patients needing kidney, liver, pancreas, heart or lung transplants.

This program also interfaces with the Cancer Signature Program (blood and marrow transplantation) and the Cornea Transplant Program. Transplantation expertise is consolidated in Ohio State’s Comprehensive Transplant Center (CTC), which was established in 2005 as the only comprehensive adult transplant program in central Ohio.

By creating a forum for collaboration among experts from multiple transplantation disciplines, the CTC team transfers best practices across specialties to enhance care.

Transplantation Signature Program highlights of 2008 • 259 patients received solid organ transplants at Ohio State’s Medical Center, including 194 kidney, 17 liver, 29 kidney/pancreas, six pancreas, one lung and 14 heart transplants.

• CTC investigators initiated or maintained 18 separate clinical trials of innovative immunosuppressive strategies in organ-transplant recipients.

• A surgery resident received the 2009 American Society of Transplant Surgeons – National Kidney Foundation Folkert Belzer, MD Research Award, which will support research in transplantation/transplant immunobiology.

• Veterinary Medicine researchers received a University Clinical and Translational Science Award training grant to support collaboration with transplantation and immunology research groups in the CTC. Transplantation Program Steering Committee: Ken Andreoni, MD John Davis, MD, PhD Michael Grever, MD Gregg Hadley, PhD Mitch Henry, MD Susan Moffatt-Bruce, MD, PhD Todd Pesavento, MD

Carl Durrenberg spent 20 hours a week for nine years tethered to a dialysis machine.

High levels of antibodies in his blood made a kidney transplant impossible. But, through personalized desensitization therapy at Ohio State, he not only received a new kidney, but a new lease on life. Learn more http://medicalcenter.osu.edu/go/ phcstories

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Key research Programs: Notable Discoveries of 2008

In addition to our six Signature Programs, Ohio State has identified three areas of research that are instrumental to the success of the Signature Programs and the Medical Center overall. These are the top discoveries for the year in our Key Research Programs: Behavioral Medicine, Biomedical Informatics, and Genetics.

Behavioral Medicine Led by Ronald Glaser, PhD, the Institute for Behavioral Medicine Research (IBMR) houses Ohio State’s multidisciplinary program in psychoneuroimmunology, the study of social and behavioral influences on stress hormones and the immune response, which involves five colleges, seven academic departments and two other Health Sciences centers at Ohio State. Researchers at the IBMR: • Discovered connections between psychosocial stress and perinatal health outcomes (Lisa Christian, PhD).

• Devised a psychological intervention that improved mental health and potentially biological outcomes in cancer patients (Barbara Andersen, PhD) • Developed an animal model to show that positive social interaction improves stroke recovery (Courtney DeVries, PhD).

• Published a paper in the journal Psychoneuroendocrinology indicating that, despite the popularity of aromatherapy, data show no positive immune or endocrine changes from the tested pupported stimulant or relaxant. (Janice KiecoltGlaser, PhD; William Malarkey, MD; Ronald Glaser, PhD)

Biomedical Informatics With scientists and clinicians generating data in unprecedented amounts, health professionals need new and better ways to make use of that information. Led by Jeffrey Parvin, MD, PhD, the Department of Biomedical Informatics plays a critical role in initiatives to translate, integrate,

share and analyze information that will facilitate scientific discovery and improve medical diagnosis, treatment and patient outcomes. Researchers in the Department of Biomedical Informatics: • Developed a series of analysis algorithms and datavisualization tools for processing massive parallelsequencing data for studying the epigenetic changes associated with drug resistance in breast cancer (Kun Huang, PhD, Computational Biology).

• Conceived Supramap (http://supramap.osu.edu), an easy-to-use Web application that tracks the evolution of pathogenic viruses (H1N1, SARS) over time, space and various hosts (Daniel Janies, PhD, Genomics).

• Built a national-scale grid-computing infrastructure for translational research (Philip Payne, PhD, Center for Translational Research Computing).

Genetics Ohio State’s Human Cancer Genetics Program is aligned with the Medical Center’s Department of Molecular Virology, Immunology and Medical Genetics (MVIMG), both led by Carlo Croce, MD. Researchers in MVIMG study molecular genetics of human disease and disease-causing organisms. Their expertise ranges from basic biophysical analysis to clinical translation in molecular genetics of cancer, immunology and immunogenetics, and bacterial and viral pathogenesis. Researchers in the Genetics Program: • Discovered a new molecular basis for the development of hormone-resistant breast cancer • Found genetic alterations that convert an indolent chronic lymphocytic leukemia to an aggressive form of the disease • Discovered that miR-29 loss is the major alteration in rhabdomyosarcoma, a malignant soft-tissue tumor found most often in children.

The Ohio State University Medical Center

Major Research centers affiliated with the Ohio STate University Medical Center

Several interdisciplinary health sciences programs at Ohio State have become so prominent that they attract significant external funding and merit their own administrative structure.

Here is a synopsis of Ohio State’s major research centers, the work they do, and the talented researchers and clinicians that lead them.

CENTER FOR ADVANCED ROBOTIC SURGERY Ronney Abaza, MD, Co-Director Jeffrey Fowler, MD, Co-Director The Center explores the expanded use of robotic surgical technology in fields such as cardiothoracic surgery, gynecology (benign), ear-nose-throat, and general surgery.

CENTER FOR BIOSTATISTICS David Jarjoura, PhD, Director The Center for Biostatistics provides expertise in study design, data management and statistical analysis for clinical, epidemiological, public health and laboratory research.

CENTER FOR CLINICAL AND TRANSLATIONAL SCIENCE (CCTS) Rebecca Jackson, MD, Director Established in 2008 through a $34 million Clinical and Translational Science Award from the NIH, Ohio State’s CCTS is one of only 38 such centers in the United States.

The CCTS supports the development of improved methods for analyzing research data and managing clinical trials in an effort to accelerate the translation of laboratory discoveries into better patient care. Read more on page 8.

CENTER FOR EDUCATION AND SCHOLARSHIP (CES) Carol Hasbrouck, MA, Director The CES supports research and scholarship in teaching and learning to enhance the quality of health sciences education for faculty, staff and trainees.

CENTER FOR IT INNOVATION IN HEALTH CARE (CITIH) Herb Smaltz, PhD, Co-Executive Director Jeffrey Parvin, MD, PhD, Co-Executive Director The CITIH produces innovative IT informatics platforms for use by the healthcare and biomedical sciences community.

CENTER FOR MICROBIAL INTERFACE BIOLOGY (CMIB) Larry Schlesinger, MD, Director The CMIB promotes and coordinates interdisciplinary research and training opportunities in infectious diseases, microbial pathogenesis and biodefense.

CENTER FOR MINIMALLY INVASIVE SURGERY (CMIS) W. Scott Melvin, MD, Director The CMIS focuses on clinical training, research and outcomes studies pertaining to the techniques and technology of minimally invasive surgery.

CENTER FOR MOLECULAR NEUROBIOLOGY Anthony Young, PhD, Director The Center for Molecular Neurobiology performs basic research and provides training in developmental, cellular and molecular neuroscience.

CENTER FOR WOMEN’S HEALTH Rebecca Jackson, MD, Director The Center is committed to meeting the health and wellness needs of women through comprehensive clinical care, clinical and translational research, and public education.

CLINICAL DIABETES RESEARCH CENTER (DRC) Kwame Osei, MD, Director The DRC is an interdisciplinary entity that serves as a forum for investigating new ideas, disseminating knowledge and discussing innovations in diabetes care.

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CLINICAL SKILLS EDUCATION AND ASSESSMENT CENTER Carol Hasbrouck, MA, Director The Center uses state-of-the-art technology, low- to highfidelity simulators, and actors to simulate patient-care experiences, exposing medical students to a range of procedures.

COMPREHENSIVE CANCER CENTER (OSUCCC) Michael Caligiuri, MD, Director The OSUCCC focuses on all aspects of cancer care: prevention, diagnosis, treatment, control, rehabilitation and education.

COMPREHENSIVE TRANSPLANT CENTER (CTC) Michael Grever, MD, Interim Director The CTC encompasses all solid organ and cellular transplantation programs at Ohio State, involving faculty from a wide cross-section of clinical and research programs COMPREHENSIVE WOUND CENTER (CWC) Chandan Sen, PhD, Executive Director The CWC is a hub for wound sciences and care, a researchand evidence-based center that treats patients with chronic, non-healing wounds.

DARDINGER NEURO-ONCOLOGY CENTER E. Antonio Chiocca, MD, PhD, Co-Director Herbert Newton, MD, Co-Director The Center conducts neuroscience and neuro-oncological research and focuses on the treatment of neurological diseases and the advancement of neurosurgical procedures.

DOROTHY M. DAVIS HEART AND LUNG RESEARCH INSTITUTE (DHLRI) Terry Elton, PhD, Interim Director The DHLRI is devoted entirely to studying diseases affecting the heart, lungs and blood vessels.

HEALTH SCIENCES CENTER FOR GLOBAL HEALTH (HSCGH) Daniel Sedmak, MD, Co-Director Mary Ellen Wewers, PhD, MPH, Co-Director The Center works with the University’s health sciences colleges, other campus colleges and Metro High School to build student interest in global health careers.

INSTITUTE FOR BEHAVIORAL MEDICINE RESEARCH (IBMR) Ronald Glaser, PhD, Director The IBMR conducts research in psychoneuroimmunology, the study of social and behavioral influences on stress hormones and the immune response.

JOHN A. PRIOR HEALTH SCIENCES LIBRARY AND CENTER FOR KNOWLEDGE MANAGEMENT (CKM) Pamela Bradigan, PhD, Director The Prior Library and CKM provide cost-effective access to biomedical knowledge and develop customized instructional resources for faculty, staff and students.

THE NISONGER CENTER Marc Tassé, PhD, Director The Nisonger Center works with communities to support the meaningful participation of people with disabilities of all ages through education, service and research.

OFFICE OF GERIATRICS AND GERONTOLOGY Catherine Lucey, MD, Interim Director Through teaching, research and consultation, the Office assists in the cost-effective delivery of high-quality health and social services to meet the needs of older citizens.

PRIMARY CARE RESEARCH INSTITUTE (PCRI) Larry Gabel, PhD, Director The PCRI supports interdisciplinary research in its efforts to optimize health through the development of professional literature, public policy and improved patient outcomes.

SPORTS MEDICINE CENTER Thomas Best, MD, PhD, Co-Director Christopher Kaeding, MD, Co-Director In addition to multidisciplinary research- and evidencebased activities, Center faculty serve as team physicians for the Buckeyes in all 36 varsity sports.

read more

Living up to our mission to improve people’s lives through innovation in research, education and patient care is a task we take seriously, and what you’ve read here is only the tip of the iceberg. You can read our unabridged 2009 Medical Center Research Report online at medicalcenter.osu.edu/ research, which features: • Complete details, in-depth data and investigator listings on hundreds of completed and ongoing Medical Center research programs and clinical trials.

• Descriptions of dozens of top research discoveries in multiple disciplines.

• News of recruitment successes and recent promotions within the Medical Center research community • Updates on grant awards and renewals of external funding, and the development of endowed chairs and professorships At medicalcenter.osu.edu/research, you’ll also find news from sites for all of the departments, programs and major research centers mentioned in this report, along with volumes of information about our state-of-the-art facilities, funding sources, external partnerships, educational programs, and plans for the future, as well as news and stories about the people who make Ohio State a world leader in research and a great place to work. You can also learn more about opportunities to join our team of dedicated researchers, educators and clinicians as we work together to discover and deliver personalized health care.

The DNA-inspired helix in our logo illustrates how we at The Ohio State University Medical Center translate the latest scientific discoveries into the best and most effective care for you based on your unique genetics, behavior and environment. We call it personalized health care. The logo’s abstract human form signifies our commitment to improving people’s lives, one person at a time. The red square shows our pride as part of The Ohio State University.

The vibrant colors represent the diversity of our staff, their ideas and the community we serve.

Office of Health Sciences Associate Vice President for Research The Ohio State University Medical Center 260 Meiling Hall 370 W. 9th Ave. Columbus, OH 43210 (614) 292.2595 medicalcenter.osu.edu

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