- Assistant Professor, Molecular and Comparative Pathobiology
and joint appointment Department of Medicine, Division of Cardiology
- Executive Director (SOM): Center for Resources in Integrative Biology (CRIB)
Background & Training:
Dr. Graham relocated from Canada following his undergraduate studies at the University of Guelph and Masters studies at McMaster University, where he studied several viral pathogens in the context of mucosal immunology, to work and eventually help to manage a group in the AIDS Vaccine Program at NCI-Frederick in 1997. After a two-year break from academics he returned to graduate school at Johns Hopkins, where he obtained his Ph.D from the Biochemistry, Cellular and Molecular Biology Training program in the Department of Pharmacology and Molecular Sciences under the direction of Dr. James Hildreth, where he studied the role of virion-associated lipid rafts. After his Ph.D., Dr. Graham joined the faculty as a research associate in the laboratory of Dr. Jennifer Van Eyk in Department of Medicine, Division of Cardiology at Bayview where he obtained training in proteomics and applied these skills to several cardiology related areas, including the study of a transgenic rabbit model of human hypertropic cardiomyopathy and the function of sino-atrial nodal cells. Dr. Graham used this opportunity to apply his acquired skills in proteomics to the emerging field of viral proteomics, where he has developed some of the first proteomics methods to study viruses and post-translational modifications of viral and viral associated host proteins.
I have been directly applying mass spectrometry and bioinformatics toward gaining understanding of the mechanisms involved in HIV pathogenesis in both the periphery and CNS for over a decade. It is becoming very clear that there is an integrated response to HIV infection and that metabolism works hand in hand with both the development and response to disease. From the moment that innate immune responses begin to HIV metabolic responses are engaged, from increased demand from NADPH in response to oxidative stress, to responses kynurenine metabolites that can alter both immune function in the periphery and in the CNS work co-operatively exitotoxic mechanisms mediated by excess extracellular glutamate. In this application, we are extremely well-positioned to study the cross talk between metabolism and neuroinflammation under cART therapy, and how therapeutic approaches targeting glutamate excitotoxicity might be able to prevent both the ongoing CNS damage under cART and potentially protect against treatments intended to purge latent viral reservoirs.
In additional to very targeted hypothesis driven studies, my group has been taking advantage of unbiased approaches to understanding disease by integrating information from many experimental sources. Our group has extensive experience in proteomics and more recently, we have extended our experience to the area of metabolomics and lipidomics. In my role as the Director for the School of Medicine for The Center for Resources in Integrative Biology (CRIB), we have been combining multiple data sources with MPP Pro software after careful validation through our method specific workflows. We have used these approaches to reveal new potential biomarkers of HAND as described within this application. In this application, I will work directly with Dr. Slusher as the Co-PI of project 3 bringing experience in bioinformatics and data integration to help elucidate how antagonists of AMPA receptor and other glutaminergic pathways mediate their effects to prevent HAND in the TAT mouse model. Also as the Co-PI for the BSL-3/Analytical Measures core, I will not only support similar measures in other projects, but will support novel methods like phosphopeptide enrichment in Project 2 and metabolite and protein measures from the CSF and brain in project 1.
Committees / Panels:
American Heart Association - Committee: Basic Cell and Molecular Biology 2, National Committee, Reviewer, Appointed from March 2006 to March 2010
Maryland Industrial Partnerships (MIPS), Reviewer
Department of Health & Human Services – Cardiovascular Sciences Small Business Activities Review Committee, Reviewer