About Us
Michael D. George, Ph.D.
University of California, Davis One Shields Avenue
Rm 5212 Genome and Biomedical Sciences Building
Davis, California 95616
Tel: (530) 530-754- 7242
Lab: (530) 752-3542
FAX: (530) 754-7240
mdgeorge@ucdavis.edu
Rm 5212 Genome and Biomedical Sciences Building
Davis, California 95616
Tel: (530) 530-754- 7242
Lab: (530) 752-3542
FAX: (530) 754-7240
mdgeorge@ucdavis.edu
Education
University of California, Davis B.S. Biology
California State University , Sacramento Teaching Credential
University of California, Davis Ph.D. Microbiology
California State University , Sacramento Teaching Credential
University of California, Davis Ph.D. Microbiology
Research Interest
HIV/SIV pathogenesis, mucosal immune system
Current Program
* Expression analysis of host innate and acquired anti-HIV/SIV responses
* Effects of antiretroviral therapeutic regimes on mucosal microenvironment
* Analysis of SIV pathogenesis in the oral cavity
* HIV and SIV associated enteropathy and regeneration of mucosal immune system
Studies in our lab are focused on understanding the molecular mechanisms that characterize host response to HIV infection in humans and SIV infection in the rhesus macaque primate model. Unlike the peripheral blood compartment, dramatic changes in T cell homeostasis and epithelial barrier function occur in gut-associated lymphoid tissue (GALT) early during primary HIV/SIV infection. In both humans and macaques, a combination of massive CD4+ T cell depletion and CD8+ T cell expansion has been demonstrated in GALT within the first few weeks of infection. We hypothesize that the degree of disruption in mucosal T cell homeostasis is correlated to the level of dysfuntion within the epithelium, and ultimately, the severity of disease progression. We are utilizing high throughput technologies such as DNA microarray and proteomic analyses to determine, at the whole genome level, comprehensive changes in host respone and gatrointestinal function that occur in GALT during various stages and outcomes of SIV/HIV infection, and in response to anti-retroviral treatments. We are currently identifying and comparing expression profiles of individual cell populations such as epithelial cells and lymphocyte subsets within GALT utilizing laser capture microdissection and mRNA amplification technologies. By elucidating molecular correlates of both negative (AIDS) and positive (long-term non-progressors) disease outcomes in humans and in the primate model, we hope to increase our understanding of HIV/SIV pathogenesis, further define the immunological relationship between human and non-human primates, evaluate the efficacy of anti-retroviral strategies at the molecular level, and identify novel potential drug targets.
* Effects of antiretroviral therapeutic regimes on mucosal microenvironment
* Analysis of SIV pathogenesis in the oral cavity
* HIV and SIV associated enteropathy and regeneration of mucosal immune system
Studies in our lab are focused on understanding the molecular mechanisms that characterize host response to HIV infection in humans and SIV infection in the rhesus macaque primate model. Unlike the peripheral blood compartment, dramatic changes in T cell homeostasis and epithelial barrier function occur in gut-associated lymphoid tissue (GALT) early during primary HIV/SIV infection. In both humans and macaques, a combination of massive CD4+ T cell depletion and CD8+ T cell expansion has been demonstrated in GALT within the first few weeks of infection. We hypothesize that the degree of disruption in mucosal T cell homeostasis is correlated to the level of dysfuntion within the epithelium, and ultimately, the severity of disease progression. We are utilizing high throughput technologies such as DNA microarray and proteomic analyses to determine, at the whole genome level, comprehensive changes in host respone and gatrointestinal function that occur in GALT during various stages and outcomes of SIV/HIV infection, and in response to anti-retroviral treatments. We are currently identifying and comparing expression profiles of individual cell populations such as epithelial cells and lymphocyte subsets within GALT utilizing laser capture microdissection and mRNA amplification technologies. By elucidating molecular correlates of both negative (AIDS) and positive (long-term non-progressors) disease outcomes in humans and in the primate model, we hope to increase our understanding of HIV/SIV pathogenesis, further define the immunological relationship between human and non-human primates, evaluate the efficacy of anti-retroviral strategies at the molecular level, and identify novel potential drug targets.
Key References
1. George, M.D., Reay E., Sankaran S., and S. Dandekar. 2005. Early Antiretroviral Therapy for Simian Immunodeficiency Virus Infection Leads to Mucosal CD4+ T-Cell Restoration and Enhanced Gene Expression Regulating Mucosal Repair and Regeneration. J Virol. 79:2709-2719.
2. George, M.D., Sanarkan, S., Gelli, A.C., and S. Dandekar. 2003. High throughput gene expression profiling indicates loss of intestinal growth factors and cell cycle mediators during primary simian immunodeficiency virus infection. Virology. 312:84-94.
3. Sankaran, S., Guadalupe, M., Reay, E., George, M.D., Flamm, J., Prindiville, T., and S. Dandekar. 2005. Intestinal mucosal T cell responses and gene expression profiles correlate with protection against disease in long-term HIV-1 infected non-progressors . PNAS 102:9860-9865
2. George, M.D., Sanarkan, S., Gelli, A.C., and S. Dandekar. 2003. High throughput gene expression profiling indicates loss of intestinal growth factors and cell cycle mediators during primary simian immunodeficiency virus infection. Virology. 312:84-94.
3. Sankaran, S., Guadalupe, M., Reay, E., George, M.D., Flamm, J., Prindiville, T., and S. Dandekar. 2005. Intestinal mucosal T cell responses and gene expression profiles correlate with protection against disease in long-term HIV-1 infected non-progressors . PNAS 102:9860-9865