Medical Student Research Fellowship for Summer 2010
Mentor: Andrew Y. Koh, M.D.
Room number: H3.104
Mail Code: 9063
Phone number: 648-8802
Project title: Effect of Fibroblast Growth Factors on the Virulence of Candida albicans
Human subjects IRB approved project number (where applicable):
Animal subjects IRB approved project number (where applicable): 2009-0243
Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic and Animal-based
Brief Description of Project:
C. albicans fungemia is a major cause of morbidity and mortality in cancer patients. Both neutropenia and GI mucosal disruption are necessary to produce a fatal disseminated infection in mice. In response to mucosal damage, the host releases growth factors (FGF-7, FGF10) that are responsible for epithelial cell regeneration. Surprisingly, we have preliminary data revealing that FGF-7 binds/attaches to C. albicans, increases C. albicans's ability to transmigrate through a GI epithelia, and augments C. albicans's cytotoxic activity on human GI cells. Furthermore, KGF appears to activate a C. albicans MAPK pathway that is critical for controlling virulence factors such as morphogenesis, invasion, and response to oxidative stress. Therefore, we now hypothesize that when epithelial mucosal tissue is damaged (i.e., chemotherapy, surgery), endogenous KGF is released by the host in order to repair these tissues. Endogenous KGF activates C. albicans virulence pathways that allow the fungus to cause severe disseminated disease.
The project will involve basic microbiological techniques (growing and culturing C. albicans, methods of documenting enumeration by spectroscopy and/or use of hemacytometer, etc.), mouse work (utilizing a murine model of C. albicans GI colonization and immunosuppression-induced dissemination), making of solutions and buffers, recombinant protein synthesis and purification via affinity chromatography), and some molecular biology methods (RNA/DNA extraction, PCR).
Previous Research Activities or Publications with Medical Students:
1. Koh AY, Priebe GP, Pier GB. A murine model of gastrointestinal colonization and dissemination during neutropenia for studying virulence of Pseudomonas aeruginosa. Infection and Immunity 2005; 73(4):2262-2272.
2. Koh AY, Köhler JR, Coggshall KT, Van Rooijen N, Pier GB. Mucosal damage and neutropenia are required for Candida albicans dissemination. PLoS Pathogens 2008; 4(2):e35.