Overview

In June of 2015, the March of Dimes joined with the University of Chicago, Northwestern and Duke to launch the fifth prematurity research center aimed exclusively at finding the unknown causes of premature birth. This demonstrates the commitment and enthusiasm of accomplished directors, investigators and faculty as they come together in this transdisciplinary and cross-institutional effort to solve the mysteries of premature birth. This team will collaborate with the other four centers as they pursue the challenging questions of what causes premature birth, and specifically address five interrelated transdisciplinary research themes around gene regulation.

The research team at the March of Dimes Prematurity Research Center UChicago-Northwestern-Duke includes over 30 faculty-level co-investigators and is lead by program director, Carole Ober, Ph.D., working along side participating co-investigators Marcelo Nobrega, M.D., Ph.D., Greg Crawford, Ph.D., Vincent Lynch, Ph.D., John Kessler, M.D., William Grobman, M.D., M.B.A., Amy Murtha, M.D., and Sarosh Rana, M.D.  

 

Program Director

Carole Ober, Ph.D. is the Blum-Riese Professor, Chair of the Department of Human Genetics, and a member of the Department of Obstetrics and Gynecology and the Institute of Genomics and Systems Biology at the University of Chicago. Dr. Ober has studied the genetics of human reproduction and fertility traits for over 30 years. In 1986, she initiated a prospective study of pregnancy outcomes in Hutterite couples that is still ongoing. As part of these studies, her team characterized the role of matching for classical HLA alleles between partners on reproductive outcome, elucidated the effects of maternal HLA-G genotypes on fetal loss rates, and conducted the first genome-wide association study (GWAS) of male fertility. In addition, she was principal investigator on the “Recurrent Miscarriage (REMIS) Study” from 1992–99, the only NIH-funded multicenter clinical trial to evaluate the efficacy of paternal mononuclear cell immunization as a treatment for recurrent miscarriage, and has conducted genetic studies of recurrent miscarriage and preeclampsia in Chicago area patients. Her current studies integrate gene expression and eQTL mapping in endometrial cells with genetic studies of fertility to identify functional variants that influence pregnancy outcome. She is a member of the NIH Infectious, Reproductive, Asthma, and Pulmonary Conditions (IRAP) Study Section, and is a Fellow of the American Association for the Advancement of Science. She received her M.A. and her Ph.D. from Northwestern University.

Co-Investigators

Haywood Brown, M.D., is the President-Elect to the American College of OB/GYN. He has served as the Co-Medical Director for the Indianapolis Healthy Babies Project and was active with the Indiana Perinatal Network, which is dedicated to decreasing infant mortality and the racial disparity for infant mortality. He has also chaired the steering committee for the District of Columbia National Institutes of Health Initiative on Infant Mortality Reduction. Dr. Brown is especially committed to the care of women at high risk for adverse pregnancy outcome, particularly those disadvantaged. He has served on the Board of Directors for the Society for Maternal Fetal Medicine and is past President of the Society. He is past President of the American Gynecological Obstetrical Society (AGOS). He also served as a Director of the American Board of Obstetrics and Gynecology. Dr. Brown is immediate past president of the North Carolina Obstetrical and Gynecological Society and is currently District IV Chair of ACOG.

Greg Crawford, Ph.D. Dr. Greg Crawford is an assistant professor in the Department of Pediatrics in the Division of Medical Genetics and a member of the Center for Genomics and Computational Biology at Duke University. Dr. Crawford specializes in mapping and characterizing active regulatory elements. He pioneered a high-throughput method (DNase-seq) to identify all DNase hypersensitive sites across the genome, which accurately mark all types of active gene regulatory elements, including promoters, enhancers, silencers, insulators, locus control regions, active histone modifications and most transcription factor binding sites. This technology is robust, highly reproducible and can be performed on any cell type from any species with a sequenced genome. Dr. Crawford was principal investigator of an ENCODE grant to map all DNase hypersensitive sites throughout the human genome from 100 diverse human cell types, including immortalized, primary, induced pluripotent stem cells, cells exposed to environmental insults and intact frozen tissues. He has extensive expertise in working with cells that are difficult to isolate, requiring optimized conditions, as well as cell types that are rare and of very low number. Dr. Crawford has participated in studies to identify DNA variants that alter chromatin accessibility (i.e., chromatin QTLs), which provides a direct mechanism to how non-coding DNA variants lead to altered gene expression. In addition, Dr. Crawford has extensive experience in performing ATAC-seq, which is an orthogonal assay to identify regulatory elements that requires as little as 10 mg. of frozen tissue. He received his Ph.D. from the University of Michigan and did his postdoctoral work at the National Human Genome Research Institute.

William Grobman, M.D., M.B.A. Dr. William Grobman is the Arthur Hale Curtis Professor and vice-chair in the Department of Obstetrics and Gynecology at Northwestern University Feinberg School of Medicine. Dr. Grobman is a maternal-fetal medicine physician whose research has focused on prediction and prevention of adverse obstetric health outcomes. His studies include evaluations of sleep abnormalities and premature birth, chronic stress and premature birth, and progesterone supplementation and premature birth. Additionally, he served as a principal investigator at Northwestern on multiple multicenter collaborations, including the Maternal-Fetal Medicine Units Network, the National Standard for Normal Fetal Growth, the nuMoM2b study, and a study of asthma in pregnancy, all of which involved the analysis of specimens collected longitudinally during pregnancy. Dr. Grobman received his M.D. from Harvard Medical School and his M.B.A. in health sciences administration and decision sciences from the Kellogg School of Management.

John “Jack” Kessler, M.D. Dr. Jack Kessler is the Ken and Ruth Davee Professor of Stem Cell Biology in the Department of Neurology at Northwestern University Feinberg School of Medicine. Dr. Kessler investigates stem cell biology and approaches to regeneration of damaged or diseased organs. He began his studies of the basic biology of neurotropic factors in both the developing and adult nervous system more than 30 years ago. He later translated this work into clinical trials of recombinant growth factors for neuropathy followed by a recent successful multicenter gene therapy trial in diabetic neuropathy. He began studying the basic biology of neural stem cells more than 25 years ago with a specific focus on defining mechanisms governing commitment of the cells to the neuronal and glial lineages. His studies of embryonic stem cells began almost 15 years ago, and he was granted one of three NIH Centers of Excellence in human embryonic stem cell research. More recently, he was granted an NIH P30 grant to support his work with induced pluripotent stem cells. He is also a co-principal investigator on an NIH Biophysical Research Partnership to utilize bionanotechnology to enhance recovery after damage to the nervous system. He was chairman of the Davee Department of Neurology for 12 years and is an active clinician as well as a stem cell biologist. He is the author of more than 270 scientific publications. He has won numerous awards, including a Peabody Award for his 2007 documentary film Terra Incognita: The Perils and Promise of Stem Cell Research. Dr. Kessler received his A.B. degree from Princeton University and his M.D. from Cornell University Medical College.

Marcelo Nobrega, M.D., Ph.D. Marcelo Nobrega, M.D., Ph.D. Dr. Marcelo Nobrega is a professor in the Department of Human Genetics and a member of the Institute of Genomics and Systems Biology at the University of Chicago. Dr. Nobrega works in understanding the mechanisms by which genetic mutations outside genes are linked to the increased risk to various diseases. These mutations, presumably affecting regulatory switches that control the function of genes, are similar to the ones we think may underlie preterm birth. Dr. Nobrega has participated in efforts to devise novel strategies and experimental assays to identify gene regulatory elements. He was a principal investigator of an ENCODE grant to devise strategies to map the binding of certain proteins to the human genome and to develop novel experimental approaches to examine specific classes of regulatory elements. Dr. Nobrega has modeled the impact of mutations implicated in various human diseases, such as congenital heart defects, heart failure, cancer, type 2 diabetes, obesity, and asthma. Using genomics approaches, Dr. Nobrega has identified the gene IRX3 as the strongest association to polygenic obesity in humans, and characterized the mechanisms by which mutations altering the expression of a gene called TCF7L2 also represent the strongest genetic link to type 2 diabetes in humans. His goal is to use the same suite of tools and approaches developed over the past decade in his lab to tackle the challenges of understanding the basis of preterm birth.

Vincent J. Lynch, Ph.D. Dr. Vincent Lynch is an assistant professor in the Department of Human Genetics and a member of the Institute of Genomics and Systems Biology at the University of Chicago. Dr. Lynch is a developmental and evolutionary biologist, specializing in determining the causal mechanisms that underlie the evolution of uniquely mammalian traits. He has a longstanding interest in developmental evolution, particularly the evolution of pregnancy in mammals. During both his doctoral and postdoctoral work, he studied the evolution of endometrial stromal cells, including both the evolutionary origin of novel regulatory elements that direct the progesterone response of stromal cells and the evolution of transcription factor functions important for directing the progesterone response. He has also detailed knowledge of endometrial biology and the biology of pregnancy in mammals and other vertebrates. This expertise is demonstrated through currently active research projects in the Lynch lab and through recent publications on endometrial biology and evolution. He received his M.S., Ph.D. and postdoctoral degrees in evolutionary biology from Yale University.

Amy Murtha, M.D. Dr. Amy Murtha is Interim Chair of OB/GYN and vice chair for research in the Department of Obstetrics and Gynecology and an associated professor in the Department of Pediatrics at Duke University Medical Center. Dr. Murtha’s research interests focus on premature birth, an area in which she has performed both clinical and bench research. Specifically, Dr. Murtha has led an ongoing effort to recruit pregnant subjects into blood and tissue repository from complicated and uncomplicated pregnancies. This data set of blood samples, DNA, and placental tissues offers tremendous opportunities to improve understanding of the molecular and biologic changes that occur in pathologic pregnancies. Dr. Murtha has served as the maternal-fetal medicine fellowship director as well as the obstetrics and gynecology resident research program director and has successfully mentored residents, fellows and junior faculty in the pursuit of academic careers. Dr. Murtha is the course director for a two-credit molecular technique workshop designed to train clinical fellows in basic laboratory techniques. This workshop, which Dr. Murtha developed over ten years ago, attracts participants from around the country and is now part of the Duke Clinical Research Training Master’s Program. She received her M.D. from Medical College of Pennsylvania and went on to a residency in obstetrics and gynecology and a fellowship in maternal-fetal medicine at Duke University Medical Center.

Sarosh Rana, M.D. is an associate professor in the Department of Obstetrics and Gynecology and chief of maternal-fetal medicine at the University of Chicago. Dr. Rana has worked for the past eight years with Dr. Ananth Karumanchi, a leading expert in the field of preeclampsia, at the Beth Israel Deaconess Medical Center in Boston. The main focus of Dr. Rana’s research is the use of angiogenic biomarkers for prediction of preeclampsia-related adverse maternal and fetal outcomes and possible use of biomarkers for risk stratification of patients with hypertensive disorders of pregnancy. Dr. Rana was the principal investigator of a recent clinical study evaluating over 2,000 patients on the utility of angiogenic factors in aiding clinicians to differentiate preeclampsia from other hypertensive disorders. As principal investigator of another recent study, she collected plasma samples and clinical data on pregnant patients, evaluating the role of angiogenic factors for patients with postpartum hypertension. As a maternal-fetal medicine specialist dealing with high risk pregnancies, Dr. Rana will have full access to patients during pregnancy and delivery and will be able to enroll a substantial number of patients for clinical pilot projects. Her undergraduate and graduate degrees are from Aligarh University in Aligarh, India. She interned at the Mayo Clinic in general surgery and followed with a residency in obstetrics and gynecology at the University of Chicago. From there, she went on to a fellowship in maternal-fetal medicine at Brown University and Women & Infants Hospital.

University of Chicago, Northwestern and Duke Theme Leaders and Co-Investigators

Research Theme 1:  Regulatory Systems Across Reproductive Tissues

Theme Leaders

Greg Crawford, Ph.D. Assistant Professor, Department of Pediatrics, Division of Medical Genetics; Member of the Center for Genomics and Computational Biology, Duke University

Marcelo Nobrega, M.D., Ph.D. Associate Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago.

Co-Investigators

Jorge Andrade, Ph.D. Director of Bioinformatics at the Center for Research Informatics (CRI), University of Chicago

Charlie Gersbach, Ph.D. Assistant Professor, Department of Biomedical Engineering; Member of the Center for Genomics and Computational Biology, Duke University

William Grobman, M.D., M.B.A. Arthur Hale Curtis Professor and Vice-Chair, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine

Chuan He, Ph.D. Professor, Department of Chemistry, Director of the Institute of Biophysical Dynamics, University of Chicago

Carole Ober, Ph.D. Blum-Riese Professor and Chair, Department of Human Genetics, Department of Obstetrics and Gynecology; Member of the Institute of Genomics and Systems Biology, University of Chicago

Tim Reddy, Ph.D. Assistant Professor, Department of Biostatistics and Bioinformatics; Member of the Center for Genomics and Computational Biology, Duke University

Sam Volchenboum, M.D., Ph.D., M.S. Assistant Professor, Department of Pediatrics; Director of the Center for Research Informatics; Associate Chief of Research Informatics Officer; Associate Director of the Institute for Translational Medicine; Member of the Institute of Genomics and Systems Biology, University of Chicago

 

Research Theme 2:  Evolutionary Systems Genetics

Theme Leader

Vincent Lynch, Ph.D. Assistant Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Co-Investigators

Greg Crawford, Ph.D. Assistant Professor, Department of Pediatrics, Division of Medical Genetics; Member of the Center for Genomics and Computational Biology, Duke University

John Kessler, M.D. Ken and Ruth Davee Professor, Department of Neurology, Northwestern University Feinberg School of Medicine

Marcelo Nobrega, M.D., Ph.D. Associate Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Tim Reddy, Ph.D. Assistant Professor, Department of Biostatistics and Bioinformatics; Member of the Center for Genomics and Computational Biology, Duke University

 

Research Theme 3:  Regulatory Variation and Networks in Premature Birth

Theme Leader

Carole Ober, Ph.D. Blum-Riese Professor and Chair, Department of Human Genetics, Department of Obstetrics and Gynecology; Member of the Institute of Genomics and Systems Biology, University of Chicago

Co-Leaders

Barbara Engelhardt, Ph.D. Assistant Professor, Department of Computer Science, Princeton University

Xin He, Ph.D. Assistant Professor, Department of Human Genetics, Member of the Institute of Genomics and Systems Biology, University of Chicago

Matthew Stephens, Ph.D. Professor, Department of Statistics, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Co-Investigators

Haywood Brown, M.D. Professor and Chair, Department of Obstetrics and Gynecology, Duke University Medical Center

Greg Crawford, Ph.D. Assistant Professor, Department of Pediatrics, Division of Medical Genetics; Member of the Center for Genomics and Computational Biology, Duke University

William Grobman, M.D., M.B.A. Arthur Hale Curtis Professor and Vice-Chair, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine

Chad Grotegut, M.D. Assistant Professor, Department of Obstetrics and Gynecology, Duke University School of Medicine

Amy Murtha, M.D. Professor and Vice Chair for Research in the Department of Obstetrics and Gynecology. Associate Professor in the Department of Pediatrics Duke University Medical Center

Marcelo Nobrega, M.D., Ph.D. Associate Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Alan Peaceman, M. D. Professor, Department of Obstetrics and Gynecology; Chief, Division of Maternal-Fetal Medicine, Northwestern University Feinberg School of Medicine

Sarosh Rana, M. D. Associate Professor, Department of Obstetrics and Gynecology; Chief, Maternal-Fetal Medicine, University of Chicago

Tim Reddy, Ph.D. Assistant Professor, Department of Biostatistics and Bioinformatics; Member of the Center for Genomics and Computational Biology, Duke University

 

Research Theme 4:  Transcriptional and Epigenetic Responses to Maternal Stress

Theme Leader

Carole Ober, Ph.D. Blum-Riese Professor and Chair, Department of Human Genetics, Department of Obstetrics and Gynecology; Member of the Institute of Genomics and Systems Biology, University of Chicago

Co-Leaders

James Collins, M.D., M.P.H. Professor, Department of Pediatrics-Neonatology, Northwestern University Feinberg School of Medicine; Medical Director, NICU, Ann & Robert H. Lurie Children’s Hospital of Chicago

Barbara Engelhardt, Ph.D. Assistant Professor, Department of Computer Science, Princeton University

Xin He, Ph.D. Assistant Professor, Department of Human Genetics, Member of the Institute of Genomics and Systems Biology, University of Chicago

Matthew Stephens, Ph.D. Professor, Department of Statistics, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Rosalind Wright, M.D., M.P.H. Horace W. Goldsmith Professorship in Children’s Health Research; Professor, Department of Pediatrics, Icahn School of Medicine at Mount Sinai

Co-Investigators

Greg Crawford, Ph.D. Assistant Professor, Department of Pediatrics, Division of Medical Genetics; Member of the Center for Genomics and Computational Biology, Duke University

William Grobman, M.D., M.B.A. Arthur Hale Curtis Professor and Vice-Chair, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine

Chad Grotegut, M.D. Assistant Professor, Department of Obstetrics and Gynecology, Duke University School of Medicine

Chuan He, Ph.D. Professor, Department of Chemistry, Director of the Institute of Biophysical Dynamics, University of Chicago

Amy Murtha, M.D. Associate Professor, Department of Obstetrics and Gynecology; Vice Chair for Research, Department of Pediatrics, Duke University Medical Center

Marcelo Nobrega, M.D., Ph.D. Associate Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Sarosh Rana, M.D. Associate Professor, Department of Obstetrics and Gynecology; Chief, Maternal-Fetal Medicine, University of Chicago

Tim Reddy, Ph.D. Assistant Professor, Department of Biostatistics and Bioinformatics; Member of the Center for Genomics and Computational Biology, Duke University

 

Research Theme 5:  Novel Cell Models of Pregnancy

Theme Leader

John Kessler, M.D. Ken and Ruth Davee Professor, Department of Neurology, Northwestern University Feinberg School of Medicine

Co-Investigators

Serdar Bulun, M.D. John J. Sciarra Professor and Chair, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine

Greg Crawford, Ph.D. Assistant Professor, Department of Pediatrics, Division of Medical Genetics; Member of the Center for Genomics and Computational Biology, Duke University

Vincent Lynch, Ph.D. Assistant Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Marcelo Nobrega, M.D., Ph.D. Associate Professor, Department of Human Genetics; Member of the Institute of Genomics and Systems Biology, University of Chicago

Chian-Yu Peng, Ph.D. Assistant Research Professor of Neurology, Ken and Ruth Davee Department, Northwestern University Feinberg School of Medicine

Tim Reddy, Ph.D. Assistant Professor, Department of Biostatistics and Bioinformatics; Member of the Center for Genomics and Computational Biology, Duke University

Teresa Woodruff, Ph.D. Thomas J. Watkins Memorial Professor of Obstetrics and Gynecology; Director of Women’s Health Research Institute; Chief, Division of Obstetrics and Genecology-Fertility Preservation, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine