Research at the Singh Laboratory
Our research interests involve many aspects of retroviral replication. We study HIV-1, Moloney murine leukemia virus, and XMRV, a xenotropic murine-like retrovirus that has been implicated in human disease.
Using the novel approach of genetic "footprinting" that we developed, our previous work involved performing a saturating mutagenesis of several retroviral sequences, thereby identifying many retroviral sequences that are essential for viral replication. We analyzed some of these regions in greater detail and determined their precise role in the viral life cycle, which included uncoating, nuclear transport of the viral replication intermediates, capsid assembly, and viral release.
We are currently examining the process of transport of HIV-1 proviral DNA into the nucleus of the infected cell. This is a very important step in the viral replication cycle and needs to occur for the viral DNA to integrate into the host chromosome. Yet, we understand very little about how it occurs. HIV DNA can enter the nucleus of non-dividing cells, and these cells can serve as a reservoir for virus that remains inaccessible to anti-viral drugs. Understanding nuclear transport of HIV-1 and designing methods to block it will be very important in addressing this otherwise inaccessible fraction of virus that is resistant to prolonged anti-viral therapy.
More recently our interest has focused on XMRV, a newly discovered xenotropic retrovirus, associated with prostate cancer and chronic fatigue syndrome in at least some studies. We continue to investigate the role played by XMRV and other related retroviruses in prostate cancer. Our experiments show that XMRV is a gammaretrovirus with protein composition and particle ultrastructure highly similar to Moloney murine leukemia virus, another oncogenic gammaretrovirus that we have studied for the last several years. We are studying XMRV replication in cultured cells and analyzing the possible mechanisms of oncogenesis by xenotropic viruses.
Our studies were the first to comprehensively and conclusively show that XMRV was not present in samples collected from patients with chronic fatigue syndrome. We continue to look for other causes of chronic fatigue syndrome, as well as work towards better ways to define and diagnose the disease.
Ila Singh, MD, PhD
1425 Madison Ave, Icahn 8-40
New York, NY 10029
The Mount Sinai Health System
One Gustave L. Levy Place, Box 1612
New York, NY 10029