Hong Gao, PhD

Advisor: Dr. Myron Jacobson
While at the University of Arizona, my research focused on the effects of poly (ADP-ribose) glycohydrolase on cellular responses to genotoxic stress. Poly (ADP-ribosyl)ation, one of the most rapid cellular responses to genotoxic stress, plays an important role in cell fate determination, promoting cell survival following limited DNA damage and increasing cell death following more extensive injury. In contrast to many genes synthesizing poly(ADP-ribose), PARG is the only well-defined enzyme to degrade this important polymer. My research has shown that alteration of PARG activity impairs DNA repair following mild genotoxic stress and increases cell death following severe genotoxic stress. Many pathological processes such as cancer, cardiovascular diseases and diabetes are related to impaired cellular responses to genotoxic stress. The role of poly(ADP-ribose) metabolism has been clearly shown in the occurrence of these diseases. Therefore, my research showing the essential role of PARG in cellular responses to genotoxic stress provides the mechanistic basis for targeting PARG as a new therapeutic strategy for multiple pathological conditions mentioned above. I am working on two projects at Louisville. One project is about the role of osteopontin in the phenotype switch of vascular smooth muscle cells (vSMC). This process is related to the pathogenesis of atherosclerosis. In the early stage of atherosclerosis, highly differentiated vSMC gain the ability to proliferate and migrate, which consequently contributes to the plaque formation. Both osteopontin protein and mRNA levels increases in the proliferative vSMC induced by allylamine. Anti-osteopontin antibody has been shown to inhibit allylamine-induced vSMC proliferation. These data strongly suggest the causative correlation between osteopontin and phenotype switch of vSMC. However, the role of osteopontin in phenotype switch of vSMC is not clear. I am working on the establishment of the specific osteopontin research tools and investigation of the role of osteopontin in the phenotype switch of vSMC using these tools. Another project is about the mechanism of selenium induced apoptosis in lung cancer cell A549. I am currently investigating the alteration of gene transcription using RT-PCR array following selenium treatment in A549 cells.
Pharmaceutical Sciences
Drug Discovery and Development
Dissertation Title: 
“Effect of Partial Poly (ADP-ribose) Glycohydrolase Gene Deletion on Cellular Responses to Genotoxic Stress”
1. Gao H, Coyle DL, Meyer-Ficca ML, Meyer RG, Jacobson EL, Wang ZQ, Jacobson MK. Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase. Exp Cell Res. 2007 Mar 10;313(5):984-96. Epub 2007 Jan 10.
Alumna or Alumnus: 
Alumni Title/Position/Employer: 
Postdoctoral Fellow, University of Louisville, KY
Career Type: