School of Medicine

Wayne State University School of Medicine

Research Faculty

My research deals with 1) the history, epidemiology and public policy issues relating to fetal alcohol syndrome; 2) the role of emotions on longevity (a recent study considered the relationship of smiling to longevity); 3) the relationship between facial features as a proxy for early testosterone exposure, and correlates with behavior, 4) the impact of names on career choices and longevity.
 
  1. Structure-function studies of the three isoforms of nitric oxide synthase and their regulation in vivo;
  2. The role of mammalian peroxidases and nitric oxide synthases in promoting oxidative stress and their potential involvement in the disease state;
  3. Identification of potent inhibitors for mammalian peroxidases and scavenger to their final products
  4. The role of reactive oxygen and nitrogen species on oocyte aging.

These projects involve the utilization of state of the art analytical methods which include enzyme purification, expression cloning, site-directed mutagenesis, and methods to study protein spectroscopy including EPR, HPLC, stopped-flow and rapid quench.

Phone: 313-577-1748
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Our laboratory investigates signaling pathways that regulate cell invasion, proliferation and aptosis during early mammalian development. Studies of pre- and peri-implantation development using cultured rodent and non-human primate embryos, as well as human trophoblast and stem cell lines, address health issues related to infertility and obstetrical pathologies. In addition to receiving extramural research support from the National Institutes of Health (NIH), we operate within the NIH Division of Intramural Research and serve as the Peri-Implantation Development Laboratory for the NICHD Program in Reproductive and Adult Endocrinology.

Ongoing investigations examine how extracellular matrices, growth factors and oxygen concentrations unique to the mammalian conceptus regulate trophoblast survival and differentiation during blastocyst implantation and placentation. Much of the work has centered on intracellular signaling mediated by members of the epidermal growth factor (EGF) signaling system. For example, heparin-binding EGF-like growth factor is drastically reduced in preeclampsia, a disorder characterized by poor trophoblast survival and decreased invasion of maternal tissues. As key mechanisms regulating the EGF signaling system and trophoblast functions are resolved, they can be examined for possible roles in pregnancy failure or obstetrical disorders.
 

Kang Chen, Ph.D,
Assistant Professor
Obstetrics-Gynecology
Email: kchen@med.wayne.edu
Phone: 313-577-8910
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Our group seeks to understand the regulation of systemic and reproductive mucosal immunity during pregnancy, which is instrumental to maternal, fetal and child health. Specifically, we investigate the functions of adaptive and innate immune cells and the mechanisms of maternal immune tolerance to the fetus during pregnancy. By harnessing the knowledge gained from our discoveries, we aim to develop diagnostic, therapeutic and preventive strategies to reduce adverse pregnancy outcomes, infant mortality and disability. Immunological concepts and technologies are central to our scientific program. We adopt a comprehensive approach encompassing molecular, cellular, histological and immunological methods, and the use of animal models and human samples, and collaborate with leading scientists and clinicians on campus and across the country.

 
Jing Dai, Ph.D.
Research Associate - Biostatistician
Email: jdai@med.wayne.edu
Phone: 313-577-1797
 
My research focuses on the assessment and development of biostatistical methods to better facilitate reproductive science projects. Through collaborations in grant proposal and manuscript writing, I support the clinical and research faculty in the department by providing biostatistical and epidemiological services including study design, protocol development, data analysis, and sample size/power calculations. I also teach OBG7500 (Applied Statistics, Epidemiology, and Study Design) for the fellows in MFM, REI, and GO.

View full list of publications.

 
Susan Dombrowski, Ph.D.
Adjunct Assistant Professor
Email: sdombrow@med.wayne.edu
Phone: 734-205-5992
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Dr. Dombrowski is a Senior Field Applications Scientist with Genomatix Software, Inc. and has been providing software application and IT support, training, User Group meetings, and next generation sequencing (NGS) and microarray data analysis since 2009. Dr. Dombrowski specializes in teaching courses on workflows and solutions for the analysis of NGS and microarray data.  Prior to joining Genomatix and WSU, Susan worked under contract at the National Center for Biotechnology Information (NCBI, at the National Institutes of Health [NIH]), where she provided bioinformatics support and training to the NCBI user community for 7 years.
 
Susan’s extensive and diverse research experience, coupled with her 12-year history in providing informatics support, consulting and training to a wide variety of scientists, numbering in the thousands (most of whom are at the NIH), and across many disciplines, has enabled her to be on the cutting edge of the latest technological and scientific advances. Her education, research and professional life have allowed her to seamlessly transition from biotechnology, gene therapy, the human genome project, next generation sequencing, and now the field of personalized medicine. 

 
Phone: 313-577-6853
Email: sorin@wayne.edu
Lab: http://isbl-413.cs.wayne.edu/
 
Research Interests: Dr. Draghici currently holds the Robert J. Sokol, MD Endowed Chair in Systems Biology, as well as appointments as full professor in the Department of Computer Science and the Department of Obstetrics and Gynecology, Wayne State University. He is also the head of the Intelligent Systems and Bioinformatics (ISBL) in the Department of Computer Science and the head of the Systems Biology in the Perinatology Research Branch,  Eunice Kennedy Shriver National Institute for Child Health and Human Development. Professor Draghici's work is focused on research in artificial intelligence, machine learning and data mining techniques applied to bioinformatics and computational biology. He has published two best-selling books on data analysis of high throughput genomics data, 8 book chapters and over 160 peer-reviewed journal and conference papers. His research laboratory has a strong track record in developing tools for data analysis of high throughput data. His laboratory has developed 8 analysis tools in this area, tools that have been made available over the web for over 10 years to over 11,000 scientists from 5 continents. He has also co-authored 3 analysis packages in Bioconductor. His top 4 papers in this area have over 2,000 total citations, while this entire work gathered over 6,600 citations. During his 16 year appointments as faculty, he was able to attract $8,262,283 as PI and $27,418,291 as co-PI in NIH and NSF grants.
 
Phone: 313-577-1158
 
Severe early preeclampsia is a hypertensive disorder in pregnancy and the major contributor to fetal and maternal morbidity. The molecular mechanisms are widely unknown and the only cure is removal of the placenta and child delivery. Our research is focused on placental development and the underlying molecular mechanisms of disease. We develop cell and tissue based in vitro model of disease to search for novel biomarkers and potential intervention strategies using a variety of drugs and technologies to ultimately improve fetal and maternal health.
 
Phone: 313-577-1857
 
The Behavioral Medicine Laboratory was founded in 1977 by Dr. Freedman and has been continuously funded by NIH since 1979. The mission of the laboratory is to study the pathophysiology of thermoregulatory disorders to determine the influence gender upon them, and to develop behavioral and pharmacologic treatments for them. The initial studies were on Raynaud’s disease and have since grown to include the physiology of menopause, the effects of menopause upon sleep, and the pathophysiology of vascular disorders. Techniques employed by the laboratory range from molecular biology, to whole animal studies in primates, to human in vivo studies in all areas.
 
Phone: 850-745-5011
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Dr. Richard Gordon is a theoretical biologist who recently established Embryogenesis Center at the Gulf Specimen Marine Laboratory in Panacea, Florida.  He has had an extensive and prominent academic career at the University of Manitoba with leadership positions in the areas of iosystems engineering, botany, computer science, electrical and computer engineering, obstetrics and gynecology, pathology, physics, radiology and zoology.
 
With the advances brought about by the Human Genome Project, we are now approaching a new era of precision in biological science as we realize the reality of personalized medicine and are in a position to consider the physics within biology.  As biology and medicine move from a descriptive to quantitative science, it is essential that we prepare our students for the future.  Dr. Gordon, has created a novel interactive state-of-the-art, internet-based graduate course dedicated to the physics of the embryo
 
John H. Hannigan, Ph.D.
Professor
Deputy Director, Merrill Palmer Skillman Institute
Professor, Psychology and Obstetrics & Gynecology
Email: j.hannigan@wayne.edu
Phone: 313-664 -2503
 
Dr. Hannigan’s interdisciplinary and multidisciplinary research assesses the effects of prenatal exposures to drugs, especially alcohol, cocaine and toluene. See http://myprofile.cos.com/jhannig for details. This research involves studies on neurobehavioral outcomes and diagnosis, mechanisms and risk factors (e.g., socioeconomic status & maternal nutrition), and interventions aimed at ameliorating and preventing life-long consequences of prenatal drugs and alcohol. Dr. Hannigan’s current research projects focus on human/clinical studies, although he is also engaged in collaborations in basic/animal research. In both animals and children, assessments of gross morphology, neuroanatomy, neurochemistry, various function measures – especially neurobehavioral and cognitive outcomes – after prenatal alcohol or drug exposure are key.
 
The important “translational” aspects of his work have implications for clinic diagnosis and interventions, and for community outreach. Examples of recent projects are studies of the neurobehavioral assessments of children, interactions between maternal alcohol intake and poor nutrition, brain imaging studies of children involving MR spectroscopy, and devising efficient clinical screens for risk drinking during pregnancy. Dr. Hannigan’s current clinical research involves collaborators from various departments in the WSU Medical School, College of Nursing, Psychology Department, and the Merrill Palmer Skillman Institute. Dr. Hannigan has considerable experience as a successful mentor at the undergraduate, graduate and post-doctoral levels and has served on graduate committees in several interdisciplinary programs. He teaches a core course on birth defects in the Reproductive Sciences graduate program, Reproductive Sciences: Teratology (PSL7730).
 
Nardhy Gomez-Lopez, Ph.D.
Assistant Professor
Email: ngomezlo@med.wayne.edu
Phone: 313-577-8904
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Our laboratory investigates immunological pathways in normal and preterm birth in both human and animal models. Our objective is to develop novel diagnostic, therapeutic and preventive strategies to reduce adverse pregnancy outcomes, such as preterm birth. Current work focuses on the role of regulatory and effector T cells and the effect of the paternal fetal antigen during pregnancy and preterm birth. This work is carried out by using animal models (transgenic and knockout mice) and molecular biology techniques such as flow cytometry, microscopy, RT-PCR. These approaches allow the identification of phenotypes and intracellular components, such as DNA, messenger RNA for particular genes, specific surface receptors, intracellular proteins, and transient signaling events in living cells. The combination of these approaches allows the identification of etiological factors of preterm birth and other related pregnancy pathologies in humans, develop novel diagnostic, therapeutic and preventive strategies to reduce adverse pregnancy outcomes.

 

Research Goal:
To achieve a Systems Biology level understanding of the genetic mechanism(s) that controls the selection of genes for development and differentiation.

Current Research Program:
We have directed our studies toward defining how gene loci are selected for expression by the mechanism termed potentiation, i.e., the opening of chromatin domains. Understanding the selective expression of our genome is fundamental to achieving the ability to reprogram our genome, the ultimate self-help therapeutic. My laboratory is using the endogenous and transgenic human and mouse protamine gene clusters as model systems of chromatin mediated differentiation. The epigenetic studies that we are pursuing extend from nuclear structure-histone modification to the role of non-coding RNAs as modulators of gene expression. Determining how these multiple levels of control interact and feedback to the genome to modulate chromatin structure and thus transcription is explored at the genome-wide systems level. We are currently extending these analyses to the level of the single cell. This data rich environment requires us to continually develop novel analysis tools while extending our computational capacity. The use of pipelining-grid computing and other strategies for high throughput bioinformatic analyses will help draw together our understanding of gene expression, chromatin structure and nuclear architect. We are beginning to uncover the complex set of processes that lead to successful conception and a healthy child. These incorporate both the genetic and epigenetic impactors of the fetal onset of adult disease, including the delivery of spermatozoon RNAs at fertilization. This population of RNAs may provide an essential component of early paternal genome reprogramming. By understanding the architectural system that regulates this mechanism we will have opened the door to using one’s own genome as a source of self-help therapeutics.

 
Phone: 313-577-9605
 
The Applied Genomics Technology Center (AGTC) is a state-of-the-art facility encompassing a wide range of genomic technologies and the expertise and track record to work with research scientists and physicians. Services include DNA isolation, DNA sequencing, next generation sequencing, genotyping, RNA isolation, and expression analysis. The facility has both low throughput and high throughput technologies to accommodate investigators’ needs, e.g. expression analysis options include: Applied Biosystems TagMan assays, Illumina BeadArrays, Affymetrix GeneChips, and digital gene expression on the Illumina Genome Analyzer IIx.
 
Phone: 313-577-1228
 
Our lab’s focus is on intracellular communication during high-risk time periods of human embryonic development. One such period occurs as the embryo prepares to implant into the uterus and embryonic and placental trophoblast stem cells expand their populations. Soon after implantation subpopulations of stem cells normally undergo differentiation essential to survival. When insufficient stem cell proliferation occurs a proportional increase in differentiation occurs, we call this “compensatory” differentiation. At low doses of stress where no significant decrease in stem cell proliferation occurs there is no regulation of factors mediating differentiation, but at doses of stress where proliferation decreases, stress enzymes shift from stem cell survival mechanisms to organismal survival mechanisms that mediate differentiation. One example is the inactivation of an anabolic enzyme by AMP-activated protein kinase (AMPK) at low stress doses (shifting from anabolic to catabolic processes) and the AMPK-mediated loss of the potency factor, inhibitor of differentiation (ID)2 at higher stress doses (Zhong et al, 2010, Reproduction, Xie et al, 2010, Mol Repro Dev). Although stress activated protein kinase (SAPK) has no role in stress-induced ID2 loss (Zhong et al, 2010, Reproduction) required to induce placental lactogen (PL)1 hormone, SAPK does mediate stress-induced upregulation of the transcription factors that ID2 blocks that is necessary for PL1 induction (Awonuga et al, 2011).

Interestingly SAPK upregulates the first essential trophoblast stem cell lineage, but blocks a later essential trophoblast lineage (Xie et al, manuscript in preparation). Similarly, stress induces an early essential lineage in embryonic stem cell differentiation and blocks a later essential lineage (Slater et al, manuscript in preparation). We call this “prioritized” differentiation and have observed that it occurs in progeny of both stem lineages in the implanting embryo (placental and embryonic stem cell lineages). The work has significant and profound implications for the mechanisms leading to the normal high loss of embryos soon after implantation and should lead to improvements in human in vitro fertilization and assisted reproductive technologies and to isolation and maintenance of higher quality embryonic stem cells. Knowledge of compensatory and prioritized differentiation will provide alternate high throughput toxicology tests that replace or reduce the need for gestational animal testing. Prioritized differentiation should provide biomarkers (Liu et al, 2009, Placenta, Xie et al., 2011, Int Rev Cell and Molec Biol) predicted by the enhanced ratio of early to late differentiated lineages during the adaptation to stress.
 
Phone: 313-577-6688
 
Douglas Ruden is interested in how early exposures to environmental toxins such as lead affect genome-wide DNA methylation and histone modifications. He collaborates on projects on several model organisms, from the fruit fly Drosophilia melanogaster, the water flea Daphnia, honey bees and killer bees, to human neonatal dried blood spots and embryonic stem cells

Laboratory techniques include: DNA methylation analyses (BS-Seq and Infinium) and histone modification analyses (ChIP-Seq and mDIP-Seq). His laboratory collaborates with the Applied Technology Genomics Core (ATGC) which has both low throughput and high throughput technologies to accommodate investigators needs, e.g. Solexa next-generation sequencing and Illumina Bead Arrays.
 
Phone: 313-577-5433
 
Our research focuses on molecular mechanisms involved in the pathogenesis of tissue fibrosis, specifically postoperative adhesions. This involves the utilization of modern state of the art molecular biology and cell culture techniques as well as animal models. The major outcome of this work, in addition to the development of the ex-vivo model for adhesions, was the development and characterization of the adhesion phenotype in cell culture. Additionally, this cell culture system was used to test the hypothesis that hypoxia is the trigger for the development of postoperative adhesions. Parallel studies investigating the role of oxidative stress in the pathogenesis of ovarian cancer are also a major focus of our laboratory. The idea of studying ovarian cancer arose from the need to compare the effects of oxidative stress on the pathogenesis of a malignant overgrowth versus a benign overgrowth, such as postoperative adhesions. These studies resulted in the identification of biomarkers for progression and metastasis of ovarian cancer. We are currently funded through NIH.
Phone: 313-577-1337
 
Research Areas: Long-term neurobehavioral sequelae of perinatal risks, including alcohol (FAS, ARBD & ARND), cocaine, tobacco and other exposures; prevention strategies; lupus; HPV and Neoplasia; fetal growth; computer applications in perinatal medicine; medical education. Techniques and Methods: Perinatal database design and management; prenatal maternal recruitment and interviewing; management of long-term longitudinal developmental follow up studies (now out to 18 years); multivariate statistical modeling and analysis; interdisciplinary.

 

Professor Emeritus Faculty
 

  1. The effects of prenatal exposure to abused drugs (cocaine, alcohol) and the benefit/harm of perinatal treatments for preterm infants (repeated antenatal corticosteroid, omega-3 fatty acids, aggressive phototherapy) using various neurological/sensory assessment tools in human infants and animal models;
  2. The effects of cancer chemotherapy drugs and chemoprotective agents on neurological/sensory function and development; and
  3. Hearing, neurological and MRI findings in craniosynostosis children (Apert, Crouzon, Pfeiffer syndromes)
Techniques & Methods:
Diagnostic auditory brainstem responses (ABRs) in neonates, children and animal models; prenatal/neonatal/postnatal database design and management; prenatal maternal recruitment and interviewing; neurodevelopmental toxicology and teratology assessments, multivariate statistical analyses; human and animal studies.
 

Dr. Sacco is a Professor Emeritus in the Department of Obstetrics and Gynecology. He received a B.A. degree with a major in Biology from the University of Rochester (1966) and received his M.S. (1968) and Ph.D. (1971) degrees in Zoology (Reproductive Biology) from the University of Tennessee. He served as a post-doctoral fellow at the Institute for Cancer Research in Philadelphia (1971-1974) and has served on the faculty of Wayne State University School of Medicine from 1974- 2011.

His primary area of research centered on the field of immunocontraception and specifically, with target antigens associated with the zona pellucida. His early publications in this area were the first to attract interest in this particular approach to contraception vaccine development. In 1983, he became Director of the Assisted Reproductive Technologies (ART) Laboratories (In Vitro Fertilization Laboratory [IVF] and Andrology Laboratory) in the Department of Obstetrics and Gynecology where he oversaw the original construction and operation of these facilities for over 19 years. Other areas of research interest include fertilization, sperm-egg interactions and the assisted reproductive technologies.

Phone: 313-577-6853
 
My research focuses on alcohol’s effect on reproduction and lactation. During the past several years, I studied alcohol’s effect on prolactin physiology employing a lactating rat model. Using this model, studies on alcohol’s effect on oxytocin secretion were also conducted. Another area of research involves developing a clamp model in humans for alcohol infusion and use of this model for endocrine and behavioral studies.