Overview of Our Research
Study of retroviruses has led to major advances in fundamental biology including the description of the first viruses that cause tumors (1, 2) and the discovery of oncogenes (3). Description of reverse transcription (4, 5), the process by which retroviruses make cDNA from the viral RNA genome, transformed understanding of genetic information transfer, though consistent with the Central Dogma of Molecular Biology (6) (see draft with drawing by Francis Crick, below), and created new possibilities for understanding the Origin of Life (7). In this spirit, we study HIV-1 replication, pathogenesis, and immunity, with the goal of making discoveries of fundamental biological significance. The simplicity of the HIV-1 genome renders virus replication dependent upon host cell factors. The host pathology that results from infection, as well as innate and acquired immunity to HIV-1, are similarly dependent upon host factors. By identifying and characterizing cellular factors of relevance to HIV-1 and other retroviruses, including the endogenous retroviruses that constitute a large fraction of the mammalian genome, we exploit HIV-1 to probe the function of human cells. In the process we elucidate fundamental mechanisms of transcription, cell cycle regulation, innate immune detection, recombination, pluripotency, signal transduction, cytokine expression, protein folding, and antigen presentation. Though basic in nature, our research contributes to the development of drugs and vaccines that target HIV-1 and other viruses such as Ebola virus, as well as diseases such as cancer, asthma, and diabetes. Our laboratory has been continuously funded by the NIH since 1990, and has always been located at academic institutions, including Columbia University in New York, the University of Geneva in Switzerland, and now the University of Massachusetts Medical School. I have held tenured professorships at each of these Universities, where I have served as primary mentor for 19 Ph.D. students, 28 post-docs, and 29 undergrad/masters students.
A full list of publications from our lab can be found here.
A list of ongoing research projects in the lab, with a few representative publications for each topic can be found here.
References:
1. Ellerman C, Bang O. 1908. Experimentelle Leukämie bei Hühnern. Zentr Bakteriol 46:595.
2. Rous P. 1911. A sarcoma of the fowl transmissible by an agent separable from the tumor cells. J Exp Med 13:397–411.
3. Stehelin D, Varmus HE, Bishop JM, Vogt PK. 1976. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170–173.
4. Temin HM, Mizutani S. 1970. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–1213.
5. Baltimore D. 1970. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209–1211.
6. Crick F. 1970. Central dogma of molecular biology. Nature 227:561–563.
7. Gilbert W. 1986. Origin of life: The RNA world. Nature 319:618–618.
