Wendy Mars, PhD

Wendy Mars, PhD

S407 Biomedical Science Tower
200  Lothrop Street
Pittsburgh, PA 15261


Liver-Related Work

Research Background: I obtained my BS in Medical Technology at Arizona State University and am ASCP certified, having worked in a clinical cytogenetics laboratory as a Medical Technologist. Subsequently, I obtained my PhD under 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.   My thesis work 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; subsequently that led me to discover that these innate immunity genes normally exhibit copy number variations (CNVs) in the human population. For one year following graduation, I studied breast cancer genetics at MDACC before moving to the Pittsburgh area where I have resided, since 1990, with my research focusing on the study of normal and abnormal liver regeneration. 
 
Liver Research:  In Pittsburgh I began my career as a Research Associate in the Department of Pathology under the tutelage of George K. Michalopoulos, MD, PhD, where I identified the urokinase- and tissue-type plasminogen activators (u-PA and t-PA) as two stoichiometric activators of Hepatocyte Growth Factor (HGF), with u-PA now accepted to be the prime activator of HGF during normal liver regeneration.  At the time, stoichiometric activation was considered a non-conventional function for these two proteins; previously both were considered to solely function as enzymes.  Subsequently, my work evolved into the study of other non-conventional roles for u-PA and especially t-PA in the liver such as the ability of t-PA to signal through the Lipoprotein Receptor-related Protein 1 (LRP1) as a means of regulating stellate cell differentiation.  Currently my work focuses on the role of LRP1 as it relates to hepatocyte/biliary transdifferentiation.  I also have in interest in the HGF/IL-6 axis.
 
Transgenic Animals:
I am in an ongoing collaboration with Dr. George Michalopoulos, Chair, Department of Pathology, on the factors leading to liver regeneration. In this capacity, I am responsible for oversight of the large transgenic colonies maintained by both our laboratories.  Lineages are as follows: 
  • Cre recominase under an alpha feto protein enhancer driven albumin promoter (Afp/Alb)
  • Glypican transgenic under an albumin promoter
  • HGF flox crossed with a cre recombinase under an inducible tamoxifen promoter
  • HGF transgenic under a GFAP promoter
  • Integrin Linked Kinase (ILK) flox
  • LRP1 flox crossed with the Afp/Alb cre recominase
  • Lymphocyte Specific Protein 1 (LSP1) knockout 
  • LSP1 transgenic under an albumin promoter
  • MET flox crossed with a cre recombinase under an inducible tamoxifen promoter
  • MET flox crossed with the Afp/Alb cre recominase
  • MET flox crossed with a lysZ cre recominase
  • u-PA knockout
  • u-PA receptor knockout
  • In addition, for Dr. Cary Wu I maintain the following colony: Kindlin 2 flox crossed with the Afp/Alb cre recombinase

 

Director, Pathology Graduate Program and Summer Undergraduate Research Program
Associate Professor, Department of Pathology