A key component of our Program is the integration of both research and clinical activities throughout all years of training. This integration is made possible by the extensive interactions between the faculty and students in the areas of research excellence and areas of clinical excellence. Some examples of these areas include:
Stem Cell Biology, Hematopoiesis, and Hematologic Malignancies
The School of Medicine has had a distinguished scientific and training history in this area for many years. Dr. Hal Broxmeyer, former Chair of Microbiology and Immunology, was the co-discoverer of the concept of using umbilical cord blood as an alternative source of hematopoietic stem cells and pioneered its use in stem cell transplantation in humans. Dr. Broxmeyer and colleagues further pioneered the concept of inhibiting dipeptidylpeptidase 4 to enhance stem cell engraftment in adults receiving umbilical cord blood transplantation, which led to an ongoing multicenter Phase II clinical trial (NCT01720264).
Dr. Mervin Yoder, Director of the Wells Center for Pediatric Research, has made the seminal observation that the embryonic yolk sac possesses definitive hematopoietic and lymphopoietic activity that is independent of the embryo proper, in distinction to the conventional stem cell theory of hematopoiesis. These results directly bear on assays used to derive hematopoietic stem and progenitor cells from human induced pluripotent stem cells (iPSC) and embryonic stem cells (ESC), and redefine the potential origin of leukemia initiating cells in neonatal leukemias.
Dr. Reuben Kapur leads the Hematologic Malignancies and Stem Cell Biology research group within the Wells Center for Pediatric Research, and has developed a collaborative and interactive group of investigators that study oncogene-induced hematologic malignancies including FLT3-ITD-induced AML, gain-of-function KIT-induced systemic mastocytosis, oncogenic Notch-induced T-ALL, and gain-of-function SHP2-induced juvenile myelomonocytic leukemia (JMML).
The research training activities of this multidisciplinary and complementary group of basic and physician-scientists include: cellular and molecular biology of hematopoiesis, transcription factors, intracellular signals, developmental hematology, and experimental therapeutics. Faculty in this group are members of an NIH-designated Center of Excellence in Molecular Hematology (P30 grant that provides access to cutting edge technologies such as intra-vital imaging, and hematopoietic and stem cell engraftment analysis) and are strongly supported via the R01 and PO1 mechanisms. T32 awards focused on hematopoiesis (year 30 of funding currently) and gene transfer (year 16 of funding currently) exist for the support of graduate students in these areas of research. With the support of a 60 million dollar matching award from the Lilly Endowment to recruit physician scientists to IUSM, a number of new faculty have been recruited including Dr. Sophie Paczesny, who focuses on Graft-Versus-Host-Disease (GVHD) biomarker discovery and validation research.
Immunology and Infectious Disease
There was a major expansion of Immunology faculty in the mid 1990’s and with further recruitment of faculty working on infectious disease since 2006 leading to the current program in immunology and infectious disease. Like other areas of training discussed in this application, research efforts in immunology and infectious disease cross-departmental boundaries and include established investigators in Microbiology and Immunology, Biochemistry and Molecular Biology, Internal Medicine, and Pediatrics. Faculty research efforts are focused on acquired and innate immunity, inflammation, bacterial and viral pathogenesis, autoimmunity, biodefense, tumor immunology, histocompatability gene function, transformation of immune cells, and virology. The broad programmatic interactions are exemplified by the number of co-authored papers of the various faculty, and their interactions on program projects including programs focused on viral immune evasion (Blum, overall PI), and pulmonary immunity (Wilkes, overall PI). Faculty from this group oversee a number of successful discipline specific training grants on campus including programs to support research in Sexually Transmitted Disease and Pulmonary Biology as well as 2 NIH-sponsored research training grants for under-represented minority trainees. The Center for Immunobiology is an interdisciplinary center focused on understanding basic questions of autoimmunity, lung transplantation, viral immunity and tumor immunology and translating these discoveries into providing new therapies to patients. The Center is directed by Dr. David Wilkes and co-directed by Dr. Janice Blum. A Center for Pulmonary Inflammation, Asthma and Allergic Diseases Directed by Dr. Mark Kaplan also brings together faculty and trainees interested in basic and translational research related to allergy and inflammation.
Indiana University School of Medicine has a strong history of accomplishments in experimental cancer therapeutics development from the 1970s, including strategies that revolutionized the survival for testicular cancer by Larry Einhorn, a member of the Institute of Medicine and the National Academy of Sciences. The School of Medicine is an established NCI Cancer Center. Cancer Biology faculty have complementary areas of research interest with faculty in the Hematopoiesis and Gene Transfer as well as the Immunology and Infectious Disease. With the support of the Lilly Endowment physician-scientist initiative to increase the number of physician scientists at IUSM, the Cancer Center has been able to recruit multiple new outstanding training faculty including leading experts in the skeletal complications of cancer and cancer therapy (Theresa Guise, MD and David Roodman. MD, PhD) and Eliot Androphy, the Chair of Dermatology who was the former Director of the University of Massachusetts MD-PhD program). Dr. Androphy is a leader in developing experimental therapeutics for the human papilloma virus. Areas of particular focus in this area of training include: tumor angiogenesis, tumor microenvironment, identification of molecular targets for the treatment of tumors, gene delivery for the treatment of malignancies, genetic basis of malignancies, and interactions between viral pathogenesis and malignancy.
The School of Medicine has a long and distinguished history of diabetes research and training. Our researchers developed the Zucker fatty diabetic rat (which continues to be an important model for research in type 2 diabetes and obesity), have played critical roles in measuring and quantifying insulin antibodies in the worldwide human insulin clinical trials, and have made pioneering strides in the relationship between chromatin structure of β cell genes and insulin secretion in type 2 diabetes. An institution-wide effort led by the Dean has resulted in dramatic growth of diabetes research at IUSM in recent years. This effort has seen the establishment of the Center for Diabetes Research (directed by Peter Roach), and the recruitments of Michael Sturek (Chair of Cellular and Integrative Physiology), Zhong-Yin Zhang (Chair of Biochemistry and Molecular Biology), and Raghu Mirmira (director of the Wells Pediatric Diabetes Research Group, and Co-Director of the MSTP). Areas of research now include Islet Biology, Adipose Tissue Biology, Obesity Research, and Insulin signaling pathways. NIH-funded researchers in all these areas have been appointed as faculty on this MSTP training grant. The goal of the integrated diabetes program at the School of Medicine is to promote research on the molecular, biochemical and cellular basis for diabetes, obesity and related metabolic disorders in the basic science environment. Another goal is to increase the exposure of students in the basic sciences to diabetes related research, through the development of graduate programs in diabetes, obesity and related metabolic diseases (this includes a Diabetes T32 that supports pre- and post-doctoral trainees).
Neuroscience and Alcohol
Neuroscience has a long and distinguished history at IUSM exemplified by the discovery of the neurotransmitter glycine by Dr. Morris Aprison in the 1960s and the pioneering work of Dr. Sidney Ochs on axonal transport. The neurosciences are undergoing a major expansion in the school beginning with the creation of the endowed Stark Neurosciences Research Institute (SNRI). Dr. Gerry Oxford is the Director of this new institute. The mission of the SNRI is to coordinate, expand, and enhance neuroscience research and training. SNRI has 44 investigators in 6 research focus groups in pain, spinal cord injury and development, substance abuse, affective disorders, neurodegenerative disorders, and metabolic regulation. In addition, a new IU Health Neuroscience Center of Excellence facility is under construction, consisting of adjoining outpatient clinic and research buildings. The new clinic will house faculty from neurology, neurosurgery, psychiatry, physical medicine and rehabilitation, and some ENT faculty, while the new basic research building, an extension of the SNRI, is organized by clinical themes (e.g. neurotrauma, addiction, mood disorders, neurodegenerative disorders, epilepsy) rather than by departments. This new complex will dramatically facilitate translational research and training in the neurosciences when completed in 2013. One area of prominent neuroscience specialization is alcohol and drug addiction. The Indiana Alcohol Research Center (IARC), in its 24th year of continuous NIH funding, and the cadre of alcohol researchers affiliated with the center, representing one of the most successful research groups with both Indiana University and Purdue University Biomedical Engineering faculty. The research activities of the IARC are quite broad and range from studies on the molecular basis of fetal alcohol syndrome and studies on alcohol pharmacodynamics and alcoholism risk in alcoholic populations, to the role of genetic factors in brain neurochemical responses to alcohol in animal models of alcohol abuse and alcoholism. IARC investigators are structural biologists, geneticists, biomedical engineers, psychiatrists, and. The Center provides unparalleled training opportunities for students and fellows and has had a T32 award for training pre- and postdoctoral fellows for the past 20 years.
Biomolecular Imaging and Structural Biology
Imaging plays a central role in advancing modern biomedical and biophysical research. The interdisciplinary Program in Biomolecular Imaging and Biophysics offers graduate research training leading to a PhD and is designed to train talented students in the use of imaging techniques to study biological processes from the molecular to the cellular level. Core courses in the fundamentals of biomedical science are complemented by courses teaching specialized knowledge in the physical basis of cell and molecular imaging. Imaging methods studied by program faculty include: Single molecule fluorescence microscopy, confocal fluorescence correlation spectroscopy and fluorescence lifetime imaging, 2-photon fluorescence microscopy, live cell and live animal fluorescence imaging, quantum dot imaging, x-ray crystallography, visualization, computer graphics and geometric modeling. The interdisciplinary nature of the program allows students to choose from faculty in a variety of departments who have a wide range of expertise in biomedical and physical science, particularly in specialized research centers focused on alcoholism, cancer, diabetes, neuroscience, and vascular biology which further broadens the academic training of participants in our program. The program takes advantage of the NIH sponsored O’Brien Center for cellular imaging, as well as IU School of Medicine research cores in biological microscopy and in vivo imaging. Dr. Andrew Saykin, Beeler Professor of Radiology, a world leader in fMRI imaging, directs the IU Cancer Center for Neuroimaging.
The diversity of faculty in the Weldon School of Biomedical Engineering provide a wealth of research opportunities spanning the field of modern biomedical engineering. Areas of Excellence include: biomaterials and tissue engineering, biomedical imaging and optics, bio-nanotechnology and biosensors, neural engineering, orthopedic biomechanics and implants, and computational and systems biology. Contributions to the field by Purdue BME investigators include the development of the first energy-efficient implantable cardiac defibrillator, a significant commercial success; the discovery of a xenogeneic biomaterial scaffold for the repair and regeneration of human tissues that is in widespread clinical use; the invention of acoustic guidance systems for endotracheal tubes that has recently been FDA-approved; the design and synthesis of novel controlled release devices for the localized delivery of drugs, peptides, and proteins; and the development of the first fully experimental techniques to design, test, and improve artificial knee joints in concert with regional industrial partners. These contributions reflect major research strengths of the two institutions in intelligent biomaterials, orthopedic biomechanics, medical imaging, implantable devices, and tissue engineering. MSTP students in the Biomedical Engineering program are encouraged to choose a highly interdisciplinary plan of study and perform research that extends beyond traditional engineering lines into the biological and medical fields. Training in this area is integrated both horizontally (cross-disciplinary) with a range of basic scientists, engineers, and physician scientists in medicine, genetics, and orthopedics. The graduate training program of the Weldon School of BME is highly interdisciplinary. Students enrolled in the doctoral programs are encouraged to take courses and have research experiences on both the West Lafayette and Indianapolis campuses, including a required experience in clinical medicine in either the Indiana University School of Medicine or Dentistry, or the Purdue College of Veterinary Medicine. MD-PhD students who pursue research rotations at West Lafayette between year 1 and 2 of medical school receive a special stipend to cover costs associated with living in two cities.
Computational Biology and Bioinformatics
The Center for Computational Biology and Bioinformatics (CCBB) is a cross-school research center, which was established in 2003. It integrates talented faculty, diverse training programs, and strong research areas from School of Medicine, School of Public Health, School of Informatics and Computing, and School of Science. The CCBB is under the directorship of Dr. Lang Li, the T.K. Li Professor of Medical and Molecular Genetics. Together with fourteen other Center faculty members, broad computational biology research areas are covered, including genomics, system biology and system pharmacology, imaging, and structure biology. The CCBB has experienced a great deal of success in many translational research areas, such as personalized medicine, drug interaction, and drug discovery. These research areas have been and continue to be funded through numerous computational biology and bioinformatics RO1 grants and collaborative program projects (UO1 and U54) awarded to CCBB faculty members. Dr. Li’s system pharmacology research in drug interaction has brought together both molecular pharmacology mechanisms and their clinical outcomes. Having been funded by three RO1 grants, Dr. Li’s research exemplifies the success and impact of the computational biology and bioinformatics research. The CCBB faculty are mentoring a number of Ph.D. students from four different schools and almost all of the students are funded through the active grants.