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Temple University School of Medicine Researcher Chosen as Finalist for American Heart Association Katz Prize
November 21, 2013
Dr. Elrod was chosen as a finalist for the prize based on a high-throughput screening project that he developed in order to identify genes that are involved in a form of cell death known as necrosis. Necrosis is a prominent feature of many diseases and it is often contrasted with apoptosis, in which cells are eliminated in a highly controlled fashion, as during development. Dr. Elrod's research suggests, however, that necrosis may also involve intracellular signaling pathways, which has important implications for scientists' understanding of cardiovascular disease, neuropathologies, and numerous other diseases that feature cell loss.
The screening project began when Dr. Elrod was at Cincinnati Children's Hospital, working as a post-doctoral fellow under Howard Hughes Medical Institute investigator Jeffery D. Molkentin, a Katz Prize winner himself. Dr. Elrod and Molkentin utilized an elaborate robotic screen that examined the entire genome by infecting cells with nearly 78,000 different shRNA's (a technology that blocks the expression of a gene). This approach allowed them to see how inhibiting each individual gene changed the way a cell died by necrosis. Using a computational approach to analyze the data, Dr. Elrod discovered that genes that encode proteins belonging to the SNARE family were involved in necrotic cell death.
The link between SNARE proteins and necrosis was unexpected. SNAREs are best known for their role in the excitation of neurons, where in the brain they mediate the release of signaling molecules that control nervous system activity. Earlier this year three scientists were awarded the Nobel Prize in Physiology and Medicine for unraveling precisely how this process works. Dr. Elrod found that a number of different SNAREs that are involved in vesicle fusion appear to also be involved in necrotic cell death.
Dr. Elrod's findings complicate traditional distinctions between necrosis and apoptosis, and they raise questions about SNAREs and their role in non-neuronal cells. "We can now move forward and try to outline the exact components and pathways in necrosis," he said. "This will aid our selection of the best target to inhibit cell death in a variety of diseases."
Elrod has continued his investigation of necrosis since joining the faculty of Temple's Center for Translational Medicine in 2012.
"John was one of my very brightest trainees," Molkentin said. "His nomination as a Katz finalist shows his potential as one of the best junior faculty prospects around the country. Temple is very fortunate to have attracted him."
Dr. Elrod was chosen as a finalist for the Katz Prize after submitting a full-length, unpublished manuscript to an AHA review panel. The manuscript was judged on its scientific merit and quality. Letters of reference and publication history were also considered in the judging process. Each finalist was invited to deliver a presentation at Scientific Sessions 2013. Dr. Elrod's presentation was titled "A genome-wide loss-of-function screen identifies SNARE proteins as a central component of programmed cellular necrosis."
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