Ila Singh
Associate Professor of Pathology and of Medicine
M.D. University of Bombay, India
Ph.D. Yale University
Ila Singh's Lab Page
Ila Singh's PubMed Literature Search
Research
Our research has recently focused on XMRV, a newly discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome. XMRV is the first gammaretrovirus known to infect humans. While gammaretroviruses have well-characterized oncogenic effects in animals, they have not been shown to cause human cancers. Our experiments show that XMRV is indeed a gammaretrovirus with protein composition and particle ultrastructure highly similar to Moloney murine leukemia virus, another gammaretrovirus that we have studied for the last several years. We analyzed 334 consecutive prostate resection specimens and found XMRV in 27% of prostate cancers. The virus was more likely to be present in higher-grade cancers. We found that XMRV proteins are expressed primarily in malignant epithelial cells, suggesting that retroviral infection may be directly linked to tumorigenesis. We are currently investigating possible mechanisms of oncogenesis by XMRV in cultured cells, in human tumors and in a mouse model. We continue to develop more sensitive and specific tests for detection of XMRV in human specimens. We are also investigating XMRV epidemiology: its prevalence in the general population, routes of transmission and organ tropism besides the prostate. We have found that a few antiretroviral drugs that are effective against HIV are also effective against XMRV at submicromolar concentrations, and work synergistically when used together. We continue to work further on understanding XMRV replication and its inhibition by various compounds. If XMRV is shown to be the cause of prostate cancer or chronic fatigue syndrome, we would have the data necessary to set up controlled clinical trials.

Transmission electron microscopy of XMRV, a virus associated with prostate cancer and chronic fatigue syndrome.
References
1. Singh IR, Gorzynski JE, Drobysheva D, Bassit L, Schinazi RF (2010) Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome. PLoS One. Apr 1;5(4):e9948
2. Schlaberg R, Choe DJ, Brown KR, Thaker HM, Singh IR (2009) XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors. Proc Natl Acad Sci USA 106:16351-16356
3. Auerbach MR, Brown KR, Kaplan A, de Las Nueces D, Singh IR (2006) A small loop in the capsid protein of Moloney murine leukemia virus controls assembly of spherical cores. Journal of Virology 80(6):2884-2893
4. Kobayashi M, Bennett M, Bercot T, Singh IR (2006) Functional analysis of hepatitis C virus envelope proteins using a novel cell-cell fusion assay. Journal of Virology 80(4):1817-25
Updated 8/15/2010


