Curt D. Sigmund, PhD
James J. Smith & Catherine Welsch Smith Professor and Chair, Department of Physiology
Associate Director, Cardiovascular Center
Medical College of Wisconsin
Dr. Sigmund’s major areas of research focus on central nervous system and vascular mechanisms of blood pressure regulation by the renin-angiotensin system, the transcription factor PPAR-gamma, and its downstream effectors Cullin-3/RhoBTB1, investigating these using a combination of molecular biological, genetic and physiological approaches including the generation of unique transgenic and knockout models. Dr. Sigmund’s laboratory is located within the Cardiovascular Center in the Health Research Center and Medical Education buildings.
Mark Santillan, MD, PhD, FACOG, FAHA
Assistant Professor of Obstetrics and Gynecology – Maternal Fetal Medicine
Faculty, Molecular and Cellular Biology
Clinical Research Director, Maternal Fetal Tissue Bank
Co-Director, OB/GYN Residency Research
Carver College of Medicine
The Santillan lab is particularly interested in the relationship between maternal health during pregnancy and the short and long-term health effects to the mother and child. Specifically, our current work focuses on the early mechanisms involved in the development of preeclampsia, including immunological and vascular function changes during pregnancy. A central focus in the lab is investigating the predictive, preventative, therapeutic and curative potential of the arginine vasopressin pathway in preeclampsia. Leveraging the group’s novel discovery of a very early biomarker for preeclampsia and a novel mouse model for preeclampsia, our lab works to investigate the mechanistic underpinnings of the predictive and therapeutic potential of vasopressin in the management of preeclampsia in a translational manner. As a practicing academic high-risk obstetrician, Dr. Santillan is very qualified in caring for women with high risk pregnancies, in understanding their clinical management, and in conducting clinical/translational research in perinatal biology. He has been successful in conducting studies in both murine and human pregnancies. As the clinical research director and co-founder of the Maternal Fetal Tissue Bank, Dr. Santillan has significant experience in clinical data acquisition, management, and analysis as well as molecular biology techniques needed for translational studies. Furthermore, as the Principal Investigator of the Population project of the University of Iowa American Heart Association Strategically Focused Research Network in Hypertension, Dr. Santillan has developed the PREDICTV network of prenatal providers around the state of Iowa to collect samples and clinical information from a diverse cohort of pregnant women.
Manish Patankar, PhD
Professor, Obstetrics & Gynecology, Division of Reproductive Sciences
Associate Director, Endocrine and Reproductive Physiology (ERP) Program
University of Wisconsin-Madison, School of Medicine and Public Health
Dr. Manish Patankar is a Professor in the Division of Reproductive Sciences. Dr. Patankar grew up in Thane, India, a city that borders Mumbai (Bombay). His wife is a physical therapist at the American Family Children’s Hospital and they have a 7 year old daughter who is in first grade at Glenn Stephens Elementary.
Dr. Patankar graduated from the University of Bombay, India with a B.S. in Chemistry in 1987. Subsequently, he received his Masters of Science in Organic Chemistry from the University of Bombay in 1990, and his Masters of Chemistry from Old Dominion University in Norfolk, Virginia in 1993. Dr. Patankar then completed his PhD in Biomedical Sciences at Eastern Virginia Medical School/Old Dominion University in 1998.
Dr. Patankar was an instructor and Research Professor at Eastern Virginia Medical School until 2004 when he joined the department as Professor and also became a member of the UW-Madison Carbone Cancer Center. His current research includes developing diagnostic tests for ovarian cancer and preeclampsia and strategies for treating ovarian cancer.
Collaborations at UW-Madison include: Drs. Joseph Connor, David Abbott, Paul Sondel, David Beebe, Ralph Albrecht, Mark Cook, Sean Fain, Ian Rowland, Hirak Basu and and Lingjun Li. Non UW-Madison collaborations include: Drs. Mitchell Ho and Ira Pastan (National Cancer Institute), Dr. Jennifer Gubbels (Augustana College, SD), Rebecca Whelan (Oberlin College, OH), Biotech Industry: Neoclone Biotechnology (Madison), and Gentel Biosciences (Fitchburg).
Dr. Patankar teaches Endocrine Physiology, Biology 151, and lectures on immunology in several different courses on campus.
What does he do in this spare time? He loves music and watching SpongeBob with his daughter.
One of the most interesting places that Dr. Patankar has visited is Bergen, Norway.
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.
Stephanie Olivier-Van Stichelen, PhD
Assistant Professor, Biochemistry
Medical College of Wisconsin
Dr. Olivier-Van Stichelen received her PhD degree in Biochemistry from the University of Lille, France in 2012. Her work was focused on the understanding of the nutrient-sensing O-GlcNAcylation in colorectal cancer development with a special interest in diet-dependent modification of the oncogene beta-catenin.
After completion of her degree, she was appointed as a post-doctoral Fellow in the Laboratory of Cellular and Molecular Biology at the National Institute of Health, Bethesda, MD, USA. In this lab, Dr. Olivier-Van Stichelen worked on different aspects of O-GlcNAcylation during development including X-inactivation of the O-GlcNAc Transferase gene. She also developed a brain O-GlcNAcase knockout model and studied the impact of sugar consumption during pregnancy on O-GlcNAc-dependent development of metabolic homeostasis. More recently, she developed interests in understanding the importance of artificial sweeteners for offspring’s metabolism and microbiome.
Dr. Olivier-Van Stichelen established her lab at the Medical College of Wisconsin at the crossroad of sweeteners, pregnancy, development and metabolism.
Due to the global trend of growing sweetener consumption, determining the interplay between diet and pre- and post-natal development is emerging as a critical area for research. Currently, the average American eats around 22 teaspoons of added sugar every day (30 sugar cubes/day hidden in foods). This modern glucose-rich diet correlates with an increase in the prevalence of obesity, diabetes and others metabolic syndromes. Moreover, the effort to reduce sugar consumption has led people to consume more non-caloric sweeteners (Aspartame, Sucralose, Acesulfame-K…). While they appear healthier for glucose homeostasis than a high carbohydrate diet, recent studies have shown that artificial sweeteners impact glucose metabolism as well as gut microbiota, rising questions about their excessive use.
Therefore, understanding what happens when caloric and non-caloric sweeteners are metabolized is of utmost importance for public health and the focus of my research group.
O-GlcNAcylation is one of the key components of diet-responsive signaling. This unique glucose rheostat is a ubiquitous and dynamic glycosylation of intracellular proteins with approximately 1000 modified proteins described to date. Two key enzymes drive O-GlcNAc cycling: The O-GlcNAc transferase (OGT) adds the modification and the O-GlcNAcase (OGA) removes it. Although many studies have focused on the decrease or complete absence of O-GlcNAc cycling by modulating the expression or activity of OGT, only a few studies have targeted hyper-O-GlcNAcylation by disturbing OGA. Because this post-translational modification is directly dependent on glucose input, depleting OGA creates an artificial and constant hyperglycemia-induced O-GlcNAcylation state. Using Oga and Ogt knockout (KO) cellular and mouse models, we can decipher the impact of high carbohydrate diet on embryonic development.
Part of my lab is interested in understanding the impact of Non-Nutritive Sweetener (NNS) consumption through pregnancy and lactation. Although, NNS have been found in mother’s milk and in placental blood circulation, no study has focused on the fundamental effect of those non-caloric sweeteners on the developing organism.
Among the impacts described in adults are changes in intestinal hormonal secretion, glucose metabolism and most fascinating, re- duction of the gut microbiota. Nevertheless, the fundamental mechanisms of those changes are far from understood. Glycoproteins found on the surface of the intestinal epithelium define the glycocalyx and are an essential mammalian mechanism of communication with the gut microbiome. Their reciprocal relationship with the gut microbiome regulates not only nutrient breakdown, and food absorption, but also infection. We are convinced that by altering both microbiome and the detoxification process, NNS exposure in early life will impact metabolic homeostasis later in life.
Xiaowen Bai, MD, PhD
Associate Professor, Cell Biology, Neurobiology & Anatomy
Medical College of Wisconsin
Dr. Bai’s research interests are centered on the application of stem cells on disease modeling and tissue regeneration. The current major focus of the laboratory is to utilize gain- and loss-of-function approaches to examine the novel molecular mechanisms underlying the roles of non-coding RNAs, mitochondria, and genetic factors in neurodegeneration and cardiotoxicity in mice, and translate the findings to humans using stem cell-derived brain cells, heart cells, three-dimensional mini brains, and heart organoids.
Non-coding RNAs, mitochondria, and cell stress-related genes in neurodegeneration:
Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Many drugs (e.g., anesthetics), environmental factors (e.g., alcohol), diseases, and genetic risks are related to neurodegeneration. We examine the novel molecular mechanisms underlying the roles of microRNAs, long non-coding RNAs, mitochondria, immediate early and other cell stress-related genes in neurodegeneration using both mouse, and human stem cell-derived brain cell and three-dimensional mini brain models
Stem cell-mediated myocardial regeneration
Myocardial infarction is one of the major causes of death throughout the world. Currently, there is not a highly effective approach for treatment. Stem cells hold promise in repairing injured cardiac tissue. Our lab is involved in studying the effect of the transplantation of adipose tissue-derived stem cells and induced pluripotent stem cell-derived cardiomyocytes on myocardial regeneration following ischemia injury. A molecular imaging method has been developed to investigate the molecular mechanisms controlling homing, engraftment, and survival of injected cells in vivo.
The mechanisms of impaired cardioprotection under diabetic conditions
Hyperglycemia has been shown to be particularly detrimental to the cardioprotective effects, with the underlying mechanisms remaining largely unknown. We have developed and validated a clinically relevant model of functional human cardiomyocytes derived from both normal induced pluripotent stem cells (iPSCs) and diabetes mellitus iPSCs. This in vitro model of human disease will enable developmental and comparative studies of normal and diabetic cardiomyocytes to address genetic and environmental mechanisms responsible for attenuation of cardioprotection signaling in diabetics.
Paul Campagnola, PhD
Professor, Biomedical Engineering
University of Wisconsin-Madison
Campagnola’s research is directed toward developing high resolution imaging modalities. The technologies his group has developed can readily be applied to problems in eye and vision research. For example, the technique of Second Harmonic Generation (SHG) to image collagen fibrillar structure has been used by other labs to image the corneal structure. Expanding into eye research is a natural direction for the Campagnola Laboratory.
Alterations to the extracellular matrix (ECM) composition and structure are thought to be critical for tumor initiation and progression for several epithelial carcinomas, including those of the ovary and breast. Our lab develops Second Harmonic Generation (SHG) microscopy tools to quantitative assess these alterations in the stroma where we correlate the optical signatures with structural changes in the fibrillar assembly between normal and diseased tissues. This physical approach provides objective measurements that may be used to understand disease progression. To further investigate how remodeling enables invasion and metastasis in vivo we use multiphoton excited (MPE) photochemistry to fabricate biomimetic in vitro models of the ovarian ECM. The nano/microstructured models simulate the crosslinked fibrillar structure of the native ECM.
Tissue engineering has vast potential to improve human health by repair and maintenance of existing tissue or generation of replacement of tissues and organs. A major limitation has been an incomplete understanding of the underlying cell-ECM interactions that govern cell adhesion which will ultimately affect downstream functions. Our approach to this problem utilizes MPE photochemistry to create 3D biomimetic scaffolds directly from crosslinked proteins. Beginning with bio-inspired designs we will seek to achieve improved function.