INDIANAPOLIS — After two years of investment by the Indiana University School of Medicine-IU Health Strategic Research Initiative, patients are reaping the benefits of new genetic testing systems, neuroscience specialists are creating new tools to battle concussions, and top scientists have been recruited to IU to join the medical school’s research and patient care team.
With each contributing $75 million, the IU School of Medicine and IU Health created the five-year initiative in 2012 to strengthen resources and produce innovative treatments from research in neuroscience, cancer and cardiovascular disease.
“In a little more than two years, we’re already seeing important research discoveries and transformation in patient care as a result of the SRI investments,” said Jay L. Hess, M.D., Ph.D., dean of the IU School of Medicine and IU vice president for university clinical affairs.
“In each of the SRI research areas, we’re targeting our strengths to ensure that the initiative results in discoveries that will both advance science and transform how we deliver care,” Dr. Hess said.
“Our goals with the SRI were to continue developing the School of Medicine’s research enterprise and leverage that development into better patient care,” said David S. Wilkes, M.D., executive associate dean for research affairs. “I’m pleased that we’re making progress on both goals.”
Cardiovascular disease
Heart patients at IU Health quickly began seeing changes when physician-scientists in the summer of 2012 began the state’s first comprehensive program to implement genetic testing in research and clinical care in heart disease.
Research into the genetic underpinnings of heart disease has developed to the point that many cardiovascular patients — and their families — will benefit from the tests, said Peng-Sheng Chen, M.D., the Medtronic Zipes Chair in Cardiology and director of the Krannert Institute of Cardiology at the IU School of Medicine.
With Strategic Research Initiative funding, the cardiovascular program has developed the laboratory expertise and received regulatory approval to use the results of genetic tests for patient care as well as research purposes. As a result, IU Health is the first health system in the state that can do such testing without sending samples to an outside testing company, Dr. Chen said.
More than 128 patients have received genetic counseling at the cardiovascular program’s genetic clinic. In another cardiovascular program, more than 1,100 patients at the IU Health cardiac catheterization lab have agreed to provide samples for research into the relationships between genetics and the effectiveness and safety of heart drugs.
Strategic Research Initiative funding is also supporting basic science research in heart disease. One early result was a recent paper in the respected journal Nature by Ching-Pin Chang, M.D., Ph.D., associate professor of medicine, identifying a new molecule that could prove key in treating heart failure.
Neurosciences
In the neurosciences, efforts are underway to build on the IU School of Medicine’s growing expertise in concussion and other neuroscience research with Strategic Research Initiative investments. Projects underway include:
- Creating a sports-related “complex concussion” clinic at the IU Health Neuroscience Center. This project, led by Thomas McAllister, M.D., chairman of the Department of Psychiatry and a nationally recognized expert in concussions, will focus on patients whose symptoms haven’t improved as expected or are worse several weeks after their injury. Clinic patients will have the opportunity to participate in future research projects, with the goal “to better understand why some get better and some don’t after similar injuries,” Dr. McAllister said.
- Assembling a traumatic brain injury patient database. Led by Richard Rodgers, M.D., assistant professor of neurological surgery and a surgeon at Goodman Campbell Brain and Spine, specialists are collecting standardized data about each patient for which the neurological surgery group provides a consultation. Information about more than 500 patients has been collected since the project started a year ago. For now, the data can be used for quality improvement purposes such as monitoring lengths of hospital stays or infection problems. The goal is to convert it to a true research database to look at such questions as whether patient outcomes differ depending on whether they have a history of alcohol abuse, Dr. Rodgers said.
- Initiation of a cerebrovascular outcomes center, which was created as part of IU Health’s successful application for Methodist Hospital to be designated a comprehensive stroke center, the first in Indiana. The outcomes center has been capturing information on all types of stroke patients at Methodist, providing data to improve treatment and, in time, provide a resource for research, said Jason Mackey, M.D., assistant professor of neurology and director of the center. For example, in the past year, the average length of time from a stroke patient’s arrival in the emergency department until receiving a standard clot-dissolving drug was cut nearly in half.
Cancer
At the Indiana University Melvin and Bren Simon Cancer Center, a $1.4 million Strategic Research Initiative investment helped create a new precision genomics program that will conduct genetic analyses of breast cancer patients to personalize their treatments.
A team led by Bryan Schneider, M.D., associate professor of medicine, and Milan Radovich, Ph.D., assistant professor of surgery and of medical and molecular genetics, is using targeted DNA sequencing in a new clinical trial for women with triple negative breast cancer, to test whether certain treatment choices improve survival rates. Following chemotherapy and surgery, patients who are at high risk for relapse will be eligible to participate in the trial.
Those selected for the targeted DNA sequencing portion of the trial will receive individualized treatments based on the results of the analysis of their genetic makeup. The analyses will be conducted by the cancer center physicians in partnership with Paradigm, a nonprofit genomic sequencing and molecular information company. This research project has formed the platform for a clinical precision therapeutics program using genetic profiling to link novel treatments to patients with rare tumors and tumors that are resistant to treatment.
Funding from the Strategic Research Initiative and The Neurosurgery Foundation at Goodman Campbell (associated with the IU Department of Neurological Surgery) has supported a collaborative cancer and neuroscience initiative, the Brain Tumor Working Group. Led by Karen Pollok, Ph.D., associate professor of pediatrics, and Aaron Cohen-Gadol, M.D., associate professor of neurological surgery, the basic science and clinical research initiative resulted in a $300,000 IUPUI Signature Center grant to Dr. Cohen-Gadol and Dr. Pollok for the Center for the Cure of Glioblastoma.
Pilot projects
With about $5.3 million from the Strategic Research Initiative, 69 early-stage research projects have been funded at the IU School of Medicine, many of them focusing on cancer. These pilot projects are designed to develop new ideas and generate preliminary data that can then be used to seek funding from agencies such as the National Institutes of Health for full research projects. Although often key to future success, funding for such pilot work is often difficult to find.
- Strategic Research Initiative pilot projects include research on:
- Potential molecules to block the viruses that cause cervical and other cancers.
- Several types of childhood leukemia and potential new treatments.
- Several aspects of pancreatic cancer, such as identifying targets to block its spread to the liver.
- Synthesizing compounds that could improve treatment of brain cancer.
- Several issues related to heart disease and heart failure in both children and adults.
Personalized medicine
The Strategic Research Initiative also invested $504,000 to support new personalized medicine initiatives. Using a customized “laboratory on a chip” designed by the IU School of Medicine, physicians and researchers will be able to test patients for genetic differences that affect how they respond to common medications. For example, about 7 percent of all people lack the necessary enzymes to metabolize codeine properly. As a result, they get no pain relief.
The personalized medicine initiative includes plans for a long-term study of the benefits of the personalized medicine test among patients at Eskenazi Health and payment for initial use of the tests in 3,000 cardiovascular, neuroscience and cancer patients at IU Health.
Top talent
One of the important goals of the Strategic Research Initiative is to add to the IU School of Medicine’s research capabilities. Thus far, 17 accomplished new faculty members have been recruited with initiative funding assistance from well-respected universities as well as internally from IU. They are:
- Costantine Albany, M.D., assistant professor of clinical medicine, specializing in genitourinary malignancies, from the Indiana University fellowship program.
- Ching-Pin Chang, M.D., Ph.D., associate professor of medicine and a specialist in cardiac development. Formerly at Stanford University.
- Thomas Everett, Ph.D., associate research professor of medicine and a biomedical engineer with expertise in optical mapping and electrical mapping of cardiac arrhythmias. Formerly at the University of California San Francisco.
- J. Emanuel Finet, M.D., assistant professor of clinical medicine and a specialist in the genetic basis of heart failure. Formerly at Duke University.
- Jiali Han, Ph.D., chairman of the Department of Epidemiology, School of Public Health. Formerly at Harvard University.
- Steven Johnson, Ph.D., assistant professor of biochemistry and molecular biology and head of the cancer initiative’s Chemical Biology and Drug Discovery program. Formerly at the University of Washington.
- W. Aaron Kay, M.D., assistant professor of clinical medicine and head of the adult congenital heart disease program. Formerly at the Ohio State University.
- Leonidas Koniaris, M.D., professor of surgery and a specialist in the relationships between cancer and other diseases in order to improve cancer treatment outcomes. Formerly at Thomas Jefferson University.
- Bert O’Neil, M.D., the Joseph W. and Jackie J. Cusick Professor of Oncology and director of the IU Simon Cancer Phase 1 and GI programs. Formerly at the University of North Carolina.
- Hongmei Nan M.D., Ph.D., associate research professor of epidemiology and director of the epidemiology core. Formerly at the University of Maryland.
- Sophie Paczesny, M.D., Ph.D., associate professor of pediatrics and a specialist in cancer and stem cell transplants. Formerly at the University of Michigan.
- Victoria Pratt, Ph.D., associate professor of clinical medical and molecular genetics and director of the pharmacogenomics clinical diagnostic laboratory. Formerly at Quest Diagnostics.
- Safi Shahda, M.D., assistant professor of medicine and a specialist in gastrointestinal cancer, from the Indiana University fellowship program.
- Yiquing Song, M.D., Sc.D., associate professor of epidemiology in the Fairbanks School of Public Health. Formerly at Harvard University.
- Matteo Vatta, Ph.D., associate professor of medical and molecular genetics and director of the cardiovascular genetic testing laboratory. Formerly at the Baylor College of Medicine.
- Stephanie Ware, M.D., Ph.D., professor of pediatrics and a specialist in cardiac development and genetics of congenital heart disease and heart failure. Formerly at Cincinnati Children’s Hospital.
- Teresa Zimmers, Ph.D., associate professor of surgery who specializes in the muscle-wasting associated with cancer. Formerly at Thomas Jefferson University.
Clinical trials
The Strategic Research Initiative also has provided $750,000 to an initiative to link computer systems at IU and IU Health that track participants in clinical trials of new therapies. The initiative will link a system implemented by the Indiana Clinical and Translational Sciences Institute at IU, Purdue and Notre Dame for clinical trials work to its electronic counterpart at IU Health.
Combining the system will provide important benefits for patient safety because physicians will be able to quickly see whether a patient is participating in a clinical trial. The combined system will also help researchers seeking potential participants for the research trials as well as people searching for trials in which they want to participate.