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Faculty Research Descriptions

The faculty research programs involve a wide variety of approaches and model systems including human, non-human, primate, laboratory animals and domestic species. Approaches include ecological, whole animal, cell biology and molecular biology. Multidisciplinary approaches are common.

While these research descriptions are provided to give applicants a general idea of potential projects, the faculty member may have additional ongoing projects in collaboration with other faculty members and departments. Appplicants are encouraged to contact indivdual faculty members during the application process.

David H. Abbott (Wisconsin National Primate Center/Obstetrics and Gynecology) - Modulation of neuroendocrine function by social status in female primates; proximate mechanisms regulating female reproductive success; ovarian dysfunction in prenatally androgenized and obese female rhesus monkeys.

Elaine Alarid (Physiology) - The endocrine system is a complex network of hormonal signals that functions to maintain homeostatic balance under varying physiological conditions. A central component in orchestrating control of endocrine function is the anterior pituitary. The anterior pituitary integrates information from the central nervous system and peripheral organs and produces regulatory hormones that control hormone production at secondary endocrine sites. How does the pituitary interpret multiple and sometimes conflicting signals? Its response is in part, controlled by cellular concentration of hormone receptors. Our current focus is to understand the control of estrogen receptor (ER) content. We have discovered that estrogen induces rapid loss of ER by invoking proteasome-mediated proteolysis. This pathway represents a non-genomic action of estrogen that differs from its classical transcriptional activation function. Furthermore, it adds an additional level of complexity to the control of estrogen responsiveness which has been previously unappreciated.

Paul J. Bertics (Biomedical Sciences) - The research program is focused on characterizing the regulation of cell proliferation and function by growth factors and toxins (i.e., endotoxin). Accordingly, this work has direct application to the understanding of the events that are involved in the development of cancer and the mechanisms associated with the toxicity of bacterial infections. The growth factor research has centered on an examination of the structure, regulation and mode of action of the epidermal growth factor (EGF) receptor, which is a ligand-activated protein-tyrosine kinase known to be of considerable importance in cell growth control. These studies also entail an analysis of systems that can serve to regulate E GF receptor function, including protein kinase C (PKC) and growth hormone receptor-mediated pathways. Because abnormal control of the EGF receptor can lead to carcinogenesis, the work has also emphasized examining how EGF receptor kinase activity can be specified/modulated by direct receptor association with the cellular cytoskeleton, the extracellular matrix (ECM), and ECM receptors.

Ian Bird (Obstetrics & Gynecology) - Control of pregnancy-induced cell expression and function of/signalling by Angiotensin II-Type1 and -Type 2 receptors in uterine artery endothelium. Cloning and sequencing/functional characterization of ovine angiotensin II Type-1 receptor gene. Control of adrenal zonation and function by Angiotensin II and integration of adrenal and gonadal steroidogenesis in higher mammals/humans. Gestational development of zonation and function of fetal adrenal gland in sheep and primate. Also as Coinvestigator (RR Magness PI): Control of pregnancy-induced expression of endothelial Nitric Oxide Synthase and Cyclooxygenase-1 in uterine artery endothelium in order to regulate uterine blood flow.

William T. K. Bosu (Medical Sciences/School of Veterinary Medicine) - Hormonal factors involved in the reinitiation of folliculogenesis in postpartum diary cows; control of corpus luteum function - relationship of intrauterine injections to the release of prostaglandins; physiological and endocrine factors responsible for cystic ovaries and abnormal luteal function in dairy cows.

Karen Downs (Anatomy) - Developmental and genetic control of fetal and extraembryonic lineage formation during mouse gastrulation, use of mammalian stem cells in gene therapy.

Theresa M. Duello (Obstetrics and Gynecology) - Regulation of pituitary receptors for gonadotropin-releasing hormone; regulatory mechanisms responsible for the differential secretion of two hormones from the same cell or syncytium; paracrine regulatory mechanisms in the placenta.

Marc Drezner (Endocrinology) My laboratory has successfuly cloned the gene for X-linked hypophospatemia and identified a new class of hormones, phosphotonins. Research methods include using transgenic, global knockouts, and cre-lox knockout murine model systems.

Oliver J. Ginther (Animal Health and Biomedical Sciences) - Reproductive physiology of the mare including most aspects of anestrus, estrus, diestrus and pregnancy; physical interactions between the embryo and uterus in horses and cattle; basic and applied aspects of regression of the corpus luteum by prostaglandins and the uterus.

Thaddeus Golos (Wisconsin National Primate Center/Obstetrics and Gynecology) - My laboratory examines questions of placental biology relevant to human health and disease. We use both nonhuman primate models as well as human clinical materials in our studies. Under this broad focus, research areas include the transcriptional control of the specification of the trophoblast lineage (of particular interest are basic helix-loop-helix and homeobox transcription factors); maternal-fetal immune tolerance (nonpolymorphic MHC class I molecules on a subset of placental cells and their interactions with the maternal immune system), placental development and function in the clinical setting of maternal diabetes, particularly the influences of glucose and oxygen on placental vascular development, and gene therapy and gene transfer at the primate maternal-fetal interface to develop experimental and therapeutic models of utero-placental function and dysfunction.

Colin Jefcoate (Pharmacology) P450 cytochromes catalyze reactions involving transfer of oxygen atoms, usually from molecular oxygen, to a substrate. They participate in a non-specific manner in xenobiotic metabolism, including drug clearance, but also bioactive carcinogens. Other family members catalyze specific biosynthetic reactions in pathways, such as steroid synthesis.

This laboratory has recently cloned P450 (CYP1B1), which is present in steroid-regulated tissues, steroid-synthesizing tissues, and embryos. It is postulated that this gene participates in developmental regulations, confirmed by recent linkage of BYP1B1 to congenital glaucoma. This laboratory has characterized the gene and 5'-flanking sequence and study gene regulation and function in mammary and fetal cells, notably by processes in involving the Ah receptor. The laboratory studies regulation of cholesterol conversion to pregnenolone, which takes place in specialized mitochondria and initiates all steroid synthesis. The project examines how the peripheral benzodiazepine receptor and StAR protein may act to regulate this process.

Pamela Kling (Pediatrics) Current research projects are focused in the following areas: 1) Roles of Enteral Hematopoietic Growth factors in Early Development; 2) Vaculogenic Effects of Erythropoietin in the Immature Gastrointestinal Tract; 3) The Effects of Chronic Hypoxia on Erythropoiesis and Iron Metabolism in the Fetus; 4) Anemia and Iron Metabolism in the Fetus and Premature Newborn; and 5) Role of Pancrine Production of Erythropoietin in Placental Angiogenesis.

Ronald Magness (Obstetrics and Gynecology) - The direction of the Perinatal Research Laboratories and its areas of major funding include: 1) Endothelial-derived vasodilators in pregnancy: expression and signaling mechanisms; 2) Estrogen and progesterone regulation of endothelial nitric oxide and prostacyclin production as it affects uterine and systemic blood flow; 3) Uterine and placental angiogenesis, and how angiogenic factors affect uterine and placental blood flow; 4) the regulation of endothelial nitric oxide production in uterine and placental vasculature at the maternal fetal interface in both the human and ovine models; and most recently 5) the role of shear stress in modulating uterine and placental endothelial vasodilator production.

Thomas F. J. Martin (Biochemistry) - Peptide hormones and neurotransmitters mediate intercellular communication in the endocrine and nervous systems. These signaling molecules are secreted by the fusion of secretory vesicles with the plasma membrane in exocytosis, a process that is highly regulated. Two distinct secretory pathways, one involving synaptic vesicles (SVs) and the other employing dense-core vesicles (DCVs), mediate the release of fast-acting synaptic transmitters or peptide hormone and modulatory transmitters, respectively. Exocytosis of both DCVs and SVs is dependent upon and activated by increases in cytoplasmic Ca2+. Our current research is directed at elucidating the molecular machinery responsible for Ca2+-dependent DCV exocytosis. These studies are of potential relevance for understanding the molecular basis for peptide hormone, neuropeptide and modulatory transmitter secretion.

James Ntambi (Biochemistry & Nutritional Sciences) - Cellular differentiation and hormonal and dietary regulation of gene expression.

Jon S. Odorico (Surgery) - Our laboratory is interested in using embryonic stem (ES) cells to study pancreatic islet development. Despite advances in our understanding of islet ontogeny, there are still significant gaps in our knowledge. Specifically, we do not yet understand precisely how insulin secreting beta cells and other endocrine cell types within mammalian pancreatic Islets of Langerhans are specified from embryonic foregut endoderm, or what complement of transcription factors direct this fate choice. Furthermore, what is the exact phenotype of islet progenitor cells, and what are the critical epithelial - mesenchymal interactions that guide this developmental process, are important questions that have not been answered. We have recently described the derivation of islet progenitor cells and mature islet cell types expressing insulin, glucagon, somatostatin, and pancreatic polypeptide from murine ES cells induced to differentiate in culture. In this in vitro differentiation system many aspects of normal islet development are reproduced, thus offering a simple, controllable culture model in which to study islet ontogeny.

David Olive (Obstetrics and Gyecology) - My research in reproductive endocrinology has covered a variety of areas, all tied together by the common thread of understanding disease processes that alter normal hypothalamic-pituitary-ovarian-uterine functions. The disorders of primary focus have been endometriosis and uterine fibroids, with some work also in polycystic ovarian syndrome. Methodology has ranged from basic bench research to clinical trials and, recently, epidemiologic investigation. The philosophical base is to not simply report phenomenology, but rather to carefully formulate hypotheses, design experiments to test those hypotheses, and finally refine the "big picture" based upon the results of the studies. This systematic, stepwise approach to investigation is one I believe is often neglected in practice, and to this end I have written frequently about the importance of quality research as a tool for understanding disease processes.

John J. Parrish (Animal Science) - The biochemical basis and regulation of sperm capacitation; the factors responsible for male fertility both in vivo and in vitro; control and regulation of the cytoplasmic environment in sperm, eggs and embryos.

Manish Patankar (Obstetrics & Gynecology) The primary focus of my research is to devise specific methods for early diagnosis of epithelial ovarian cancer (EOC) and to understand the effect of factors produced by ovarian tumors on the functional capacity of tumor infiltrating lymphocytes. This research involves extensive utilization of glycoproteomic analysis in conjunction with cellular immunology, molecular biology and glycobiology. These studies are supported by grants from the Department of Defense and the Elsa U. Pardee Foundation. 

Richard Peterson (Pharmacology) - The goal is to determine consequences of perinatal TCDD exposure on prostate development in the C57BL/6 mouse and elucidate mechanisms involved. Specific aims. are to identify aberrant effects of TCDD on development of ventral (VP), dorsolateral (DLP), and anterior (AP) prostate, determine using AhR knockout (AhRKO) mice if these effects require AhR, determine critical periods for producing them, elucidate androgen dependent mechanisms for causing them, determine if TCDD acts directly on urogenital sinus (UGS) or prostate to inhibit development, determine if co-exposure to a natural AhR antagonist in human food, resveratrol, ameliorates TCDD disruption of prostate development, identify during the critical period TCDD responsive genes in UGS, determine using a dose response approach TCDD responsive genes in UGS that may be involved in TCDD inhibition of prostatic budding, and determine long-term consequences of perinatal TCDD exposure on prostate size, histology, and growth in senescence.

Jack Rutlledge (Animal Sciences) - Current research interests are in applications of in vitro bovine embryo production and allied technologies to animal breeding and animal production systems. I also have interests in improving the technologies; for example one of my current students (Men) has worked on vitrification of cattle oocytes. Another (Fischer-Brown) is working on dynamics of embryonic growth and development as it relates to culture medium.

Linda A. Schuler (Comparative Biosciences/School of Veterinary Medicine) - The Schuler laboratory is interested in the interactions of prolactin and related hormones with other growth factors and hormones at fetal and maternal targets during pregnancy. They have extended studies on the actions of prolactin in mammary alveolar development during pregnancy to its role in the development and progression of mammary cancer. Using a variety of in vitro models, they examine control of receptor expression including receptor internalization and linkage to signal transduction, cell specific target genes, and signaling pathways employed. They have developed transgenic mouse models using a non-hormonally responsive, mammary specific promoter in order to examine
interactions on preneoplastic processes in vivo.

Lewis G. Sheffield (Dairy Science) - Cellular and molecular regulation of mammary gland growth; mechanisms by which estrogens, progesterone and prolactin modulate EGF signaling systems; role of growth factors in modulating cell stress.

Ei Terasawa (Pediatrics, Primate Center) - Research of my laboratory focuses on the study of the hypothalamic neuroendocrine system, the luteinizing hormone releasing hormone (LHRH) neurons. The aims of the current studies are: 1) to determine the regulation of the LHRH neurosecretory system in controlling the onset of puberty; 2) to determine the mechanism of oscillatory activity of LHRH neurons; 3) to study the differentiation, development, and migration of LHRH neurons; 4) to investigate ovarian steroid action on pulsatile LHRH release; and 5) the role of the hypothalamus in menopause.

Jamie Thomson (Anatomy, Primate Center) My laboratory uses Embryonic Stem (ES) cells derived from non-human primates and humans as an in vitro model for understanding human development. Our primary focus currently is on understanding how ES cells choose between self-renewal, differentiation and apoptosis. Because of the potential applications of human ES cell-derived tissues for transplantation therapies, we also have collaborative projects on ES cell differentiation to neural, pancreatic, cardiac, and hematopoietic lineages. Our long term goal is to use non-human primate ES cells and non-human primates as a preclinical model to demonstrated the safety and efficacy of ES cell-based therapies.

Jyoti Watters (Comparative Biosciences) - My research interests are thus centered around the molecular mechanisms employed by microglia that result in the gender-specific production of pro- and anti-inflammatory cytokines/agents that are ultimately involved inthe inflammation and neurotoxicity associated with diseases and disorders of the CNS. Because women often have a higher incidence or predisposition to certain immune and neurodegenerative disorders than men, I have particular interest in investigating the role of estrogens in microglial cell production of inflammatory mediators. The focus of my studies will thus revolve around investigating the effects that adenine nucleotides and estrogens exert on microglial cell MAPK activation (e.g. p38, JNKs, ERKs) which ultimately ntrolsmicroglial cell activity and their production of inflammatory mediators. My initial studies will utilize the microglial cell lines BV-2 and N9, to identify molecular targets of estrogen and nucleotide action. Subsequent studies will involve the use of primary microglial cells derived from estrogen receptor knockout mice as well as mice possessing genetic aberrations in nucleotide receptors important for microglial cell function (i.e P2X7).

Milo C. Wiltbank (Dairy Science) - Hormonal interaction between the maternal and fetal systems during early pregnancy; intracellular regulation of cell death and steroidogenesis in the corpus luteum; regulation of ovarian function in dairy cattle.

Jing Zheng (Obstetrics & Gynecology) - My long-term goals are to determine cellular and molecular mechanisms that regulate angiogenesis and endothelial cell function, which ultimately control blood flow. My current research interests are to study effects of nitric oxide and angiotensin II on placental angiogenesis using human and ovine endothelial cell models, and signaling pathways. Specific research project include 1) determining whether in the fetoplacenta bFGF- & VEGF-induced angiogenesis is modulated in part via an increase in production of nitric oxide which in turn activates MAPK signal pathway and increases expression of bFGF & VEGF as well as their receptors; 2) determining whether newly identified VEGF receptor, neuropilin-1 and -2, are expressed in endothelial cells and their roles in placental angiogenesis and vasodilators; and 3) exploring roles of angiotensin II in regulation of angiogenesis and vasodilation. These studies, therefore, will glean important information on the mechanisms that regulate placental angiogenesis during late pregnancy and define the underlying molecular interactions of vasodilation and angiogenesis.