Pathology Graduate Training Program
Name: Gina Coudriet
Cellular and Molecular Pathology (CMP) -
Undergraduate Degree: BS
Undergraduate Degree Year: 2004
Undergraduate Institution: Northeastern University
Undergraduate Major: Biology
Academic Status: 4th Year
Graduate Program: Cellular & Molecular Pathology
Thesis Advisor: Jon Piganelli, Ph.D.
Thesis Title/Research Topic:Hepatocyte Growth Factor Regulates Inflammation in Type 2 Diabetes
Current Research Description: Type 2 diabetes (T2D) is characterized by obesity and insulin resistance. Obesity elicits chronic inflammation characterized by elevated TNF-a, IL-6 and the type 1 plasminogen activator inhibitor (PAI-1). Hepatic PAI-1 is a known to prohibit the formation of biologically active hepatocyte growth factor (HGF). Hepatectomy-induced liver regeneration begins with a minor surge of hepatic HGF, followed by the early production of IL-6 and TNF-a that wanes in concert with a second, pronounced elevation of aHGF. We hypothesize that aHGF, which is PAI-1 regulated, temporally controls these pro-inflammatory cytokines. To investigate this we sought to assess the role of HGF and how it influences regulation of inflammation. We utilized a well-defined model of inflammation, lipopolysacharride (LPS)-mediated activation of bone marrow derived macrophages (BM). BM stimulated with LPS in conjunction with HGF demonstrated a 2-fold decrease in the levels of IL-6 compared to control. HGF's decrease of IL-6 was reversed with a MET-specific small molecule inhibitor (SU11274), further supporting our hypothesis that HGF is a negative regulator of IL-6 production in BM. Since the prevailing literature indicates obesity is linked to on-going inflammation in T2D-prone obese individuals, we next assessed the role of hepatic HGF in a mouse model of T2D. C57BL/6 mice were placed on a high fat diet to induce the T2D phenotype. Obese mice exhibited an increase in circulating adipokines, became glucose intolerant and hyperinsulinemic as well as steatotic. These results correlated with increased levels of PAI-1, which lead to decreased levels of aHGF, strengthening our hypothesis that aHGF temporally controls inflammation in T2D.
Undergraduate Honors: Deans List, Faculty Undergraduate Research Institute Award
American Heart Association Pre-doctoral Fellowship Award (2006-2008). Jon D. Piganelli, Mentor.
2008 BGSA Symposium. University of Pittsburgh Interdisciplinary Biomedical Graduate Program. October 22, 2008. Pittsburgh, PA. Poster Presentation.
68th Scientific Sessions. American Diabetes Association. June 6th - 10th, 2008. San Francisco, CA. Attendance and abstract publication.
2007 BGSA Symposium. University of Pittsburgh Interdisciplinary Biomedical Graduate Program. October 24, 2007. Pittsburgh, PA. Poster Presentation.
67th Scientific Sessions. American Diabetes Association. June 22nd - 26th, 2007. Chicago, IL. Attendance and abstract publication.
2007 University of Pittsburgh School of Medicine, Department of Pathology Research Day Pathology Research Day. June 1st, 2007. Pittsburgh, Pennsylvania. Attendance and poster presentation.