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Ross Whittaker
My work in Dr. Chris Glembotski’s lab focused on the role of the small heat shock protein alpha B-crystallin in protecting the heart from ischemic injury. I was interested in understanding several different mechanisms by which alpha B-crystallin could protect the heart. The first mechanism that I explored concerned the ability of alpha B-crystallin to protect mitochondrial function and integrity during ischemia-reperfusion stress, such as during a heart attack. Alpha B-crystallin is a unique protein in that during non-stressed conditions it exists primarily in the cytosol, but upon experiencing stress it re-distributes to several different cellular locations, including the mitochondria. We were able to demonstrate that in the heart, alpha B-crystallin translocated from the cytosol to the mitochondria within 10 minutes following the onset of ischemia and that levels of alpha B-crystallin remained elevated at the mitochondria during reperfusion. We also found that alpha B-crystallin inhibited the release of cytochrome c from the mitochondria, possibly through interactions with VDAC and BAX. This work was accepted for publication in the American Journal of Physiology: Heart and Circulatory Physiology. The second mechanism that I explored concerned the effects of alpha B-crystallin on redox regulation in the heart. This work is currently in preparation for submission to a journal that is yet to be determined.
This work was funded by the NIH and through a fellowship from the Rees-Stealy Research Foundation, which I was awarded from 2005-2008. I also need to thank my fellow colleagues in Dr. Glembotki’s lab, and of course Dr. Glembotski for his excellent mentorship during my time in his lab. I would also like to thank Dr. Sandy Bernstein for his work in creating the San Diego State Ph.D./MBA program, which I had the pleasure of taking part in, and resulted in me receiving my MBA from the San Diego State School of Business in Spring 2008.
After completing my dissertation work I took a position as a research scientist at Vala Sciences, a San Diego biotech company that develops assays and software for high content image analysis. I am also working with Dr. Glembotski on developing a separate area of my dissertation research into a new start-up biotech company.
Gerardo’s work in Stanley Maloy’s lab focused on a virus called bacteriophage P22 which specifically infects Salmonella Typhimurium. Understanding how the phage DNA gets into its host could provide vital information in using phages in treating bacterial infections. Phage therapy can be used in conjunction with antibiotics to treat pathogenic infections caused by antibiotic resistant bacteria like methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, E. coli and Enterococcus faecalis. Phages and phage proteins can also be used to kill agents of bioterrorism such as Bacillus anthracis. Gerardo used phage P22 to study the mechanism of phage DNA transport across the cytoplasmic membrane of its host since a lot of information is already known about P22 and its host Salmonella. Gerardo’s experiments showed that the phage-encoded proteins (gp16, gp20, and gp7) mediate transport of DNA across liposomal membranes. Transport of 32P-labeled DNA into liposomes occurred only in the presence of gp16 and an artificially-created membrane potential. Taken together, these results suggest that gp16 mediates the active transport of P22 DNA across the cytoplasmic membrane of Salmonella.
This work was accepted by the Journal of Bacteriology for publication while the research on the bioenergetics involved in the transport of phage P22 DNA across the cytoplasmic membrane of Salmonella was submitted to FEMS Letters. Funding for these projects was provided by NIH/NIGMS MBRS 1R25GM8906-07 and by the generous support of the ARCS Foundation. I would like to take this opportunity to thank my committee members who were extremely supportive in providing me with feedback and guidance. I would also like to express my appreciation for all the help that I received from undergraduates who definitely made research fun and exciting.
I am currently pursuing three potential postdoctoral positions in San Diego. The research project at the UCSD Med Center will use phages in drug delivery and directed evolution for the treatment of cancer. The postdoc position at the UCSD Cancer Center will engineer oncolytic viruses to specifically and efficiently lyse cancer cells and the postdoc project at the La Jolla Institute of Allergy and Immunology will investigate the effects of palmitoylation of signal molecules in T lymphocytes.
