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Iranian Scientist Wins NIH 2009 Innovator Award

Saturday, October 24, 2009

Active ImagePardis Sabeti is awarded an NIH Director's 2009 New Innovator Award for research in host and pathogen evolution in Lassa fever. The award addresses two important goals: stimulating highly innovative research and supporting promising new investigators.

Disease-causing pathogens are among the most intriguing forces shaping human evolution, as they have a tremendous impact on our genome and themselves evolve over time. A genome-wide survey of human variation identified two genes biologically linked to Lassa fever as among the strongest signals of natural selection in West Africans. Lassa fever is a severe hemorrhagic disease endemic in West Africa, and our findings suggest it is an ancient selective force driving the emergence of genetic resistance. While poorly understood, Lassa fever has arguably the greatest potential impact of all infectious diseases of humans because of its unique status as both an immediate public health crisis and a category A potential bioterrorist agent.

With the aim to pursue the intriguing signal of natural selection linked to Lassa fever, we first set out to address critical gaps in knowledge, capacity, and diagnostics. We established a basic diagnostic and research lab in Irrua, Nigeria, where yearly outbreaks of Lassa fever occur with population exposure of ~30%. Preliminary data suggests our initial measures have significantly reduced fatality from an estimated 65% to 20% among Lassa fever cases. We now aim to design a robust, field-deployable diagnostic, based on genome sequencing of diverse strains, to rapidly detect and distinguish Lassa virus strains. This work addresses immediate public health needs and sets the foundations for research into the genetic factors in both virus and human that underlie resistance to Lassa fever found among many West Africans. The ultimate goal of our work is to identify natural mechanisms of defense and illuminate the evolutionary adaptations that have allowed humans to withstand some of our most complex and challenging selective agents. Moreover, these efforts will create new opportunities in Lassa virus research, including investigations of viral pathogenicity and evolution and development of novel vaccines.

Pardis C. Sabeti is an Iranian American evolutionary geneticist, who developed a statistical method which identifies sections of the genome that have been subject to natural selection. Sabeti is an Assistant Professor in the Center for Systems Biology and Department of Organismic and Evolutionary Biology at Harvard University.


Active ImageSabeti completed her undergraduate degree at MIT and continued her education at Oxford as a Rhodes Scholar, before returning to earn her medical degree from Harvard Medical School where she was only the third woman ever to graduate summa cum laude. She is also the lead singer and bass player of the Rock band Thousand Days. She has also received a Burroughs Wellcome Fund Career Award in the Biomedical Sciences.
As a postdoctral fellow with Eric Lander at the Broad Institute, Sabeti modified a family of previously developed statistical tests for positive selection that look for common genetic variants found on unusually long haplotypes. Her test, known as the cross population extended haplotype homozogysity test, or XP-EHH, was designed to detect advantageous mutations whose frequency in human populations has risen rapidly over the last 10,000 years.
The XP-EHH test, in combination with existing methods, recovered several known targets of recent natural selection, and suggested several novel targets. She also identified two variants in the genes LARGE and DMD, known to be involved in infection by Lassa fever, that show strong signals of natural selection in West Africans.

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