Dr. Wendy M. Mars

Dr. Mars obtained her BS in Medical Technology at Arizona State University and she is ASCP certified, having worked in a clinical cytogenetics laboratory as a Medical Technologist. Subsequently, she obtained her PhD working with Grady F. Saunders, PhD, at the MD Anderson Cancer Center (MDACC) studying the “Molecular Genetics of Cancer,” using Chronic Myelogenous Leukemia (CML) as a model. Her dissertation research identified the alpha-defensins DEFA1 and DEFA3 (formerly known as HP-1 and HP-3) as the most abundantly expressed genes in the chronic phase of CML. This observation led Dr. Mars to discover that these innate immunity genes normally exhibit copy number variations (CNVs) in the human population. For one year following graduation, she studied breast cancer genetics at MDACC before moving to the Pittsburgh area where she has resided, since 1990, with her research focusing on the study of normal and abnormal liver regeneration.

The main focus of Dr. Mars’ research has been to understand the roles of the urokinase- and tissue-type plasminogen activators (u-PA and t-PA) in liver regeneration, particularly with regard to their interactions with their stoichiometric target, Hepatocyte Growth Factor (HGF). Although u-PA and t-PA are best known for their enzymatic roles in fibrinolysis and cancer metastases, in the early 1990’s Dr. Mars’ research group (and others) demonstrated that u-PA and t-PA are also capable of activating latent HGF to its active form, suggesting non-canonical roles for these two proteins. Stoichiometric activation of HGF by u-PA is of particular importance during liver generation/regeneration, where HGF serves as an essential molecule for liver growth. HGF and u-PA, the u-PA inhibitor (PAI-1), and their receptors MET (for HGF), u-PAR (for u-PA), and LRP1 (for u-PA and/or t-PA), are either made or utilized by multiple liver cell types, including hepatocytes, Kupffer cells (hepatic macrophages), stellate cells, and sinusoidal endothelial cells. This poses a problem in fully understanding exactly how u-PA, HGF, and PAI-1 contribute to liver regeneration since it is difficult to discern which cell types participate in the growth/regenerative process at what times. In order to explore this area of research more fully, Dr. Mars’ research group initially developed a fluorescent in situ hybridization (FISH) technique for detection of cellular mRNAs that can be used in conjunction with protein immunofluorescence (IF). By simultaneously utilizing FISH and IF, they were able to definitively demonstrate which cell types produce particular mRNAs and proteins at any particular time during liver growth and regeneration. In addition, Dr. Mar’s research group discovered that the u-PA/HGF axis interacts with interleukin-6 (IL-6), a crucial cytokine controlling various liver responses, including the acute phase response. More recent studies have focused on investigating novel interactions between these proteins (u-PA, u-PAR, HGF, PAI-1, MET, t-PA, LRP1) and other pathways known to be important in liver homeostasis. Using a cell-specific targeted cre/loxp approach (LysZ for macrophages, albumin for hepatocytes, tamoxifen for all cell types) Dr. Mars’ group demonstrated that constitutive activation of MET in bone marrow-derived macrophages leads to suppressed IL-6 production in response to LPS stimulation. In contrast, in hepatocytes HGF acts as a direct stimulus for IL-6 production. In other investigations Dr. Mars showed that t-PA-mediated signaling through LRP1 in stellate cells reverses their activation. In kidney, t-PA actually pushes a fibrotic response through the same receptor. The implication of these latter findings is that t-PA, an FDA-approved drug, may ultimately be of value in hepatic fibrosis/cirrhosis. However, due to the potential for inducing kidney fibrosis, a way of specifically targeting treatment to the liver will be essential.

Dr. Mars is an Associate Professor in the Department of Pathology at the University of Pittsburgh, Director of the Cellular and Molecular Pathology (CMP) graduate program, and a member of the Pittsburgh Liver Research Center. She also serves as Assistant Dean for the Learning Environment and Associate Director of the Summer Undergraduate Research Program. The Cellular and Molecular Pathology (CMP) graduate program is one of 11 PhD-granting programs in the University of Pittsburgh School of Medicine. The CMP Graduate Program typically has around 25 students and Dr. Mars is responsible for oversight of the curriculum, faculty, and student affairs. As the Assistant Dean for the Learning Environment, Dr. Mars has responsibility for all graduate student learning experiences (good and bad) in the University of Pittsburgh School of Medicine. Many of these learning experiences correspond to relationships between mentors/teachers and students, and issues of equity, diversity, and inclusion. This oversight role covers around 450 graduate students at any given time. Dr. Mars is a long-time member of the ASIP and currently serves on the Program Committee and the Education Committee. 

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