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Robert F. Siliciano

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Robert F. Siliciano, MD, PhD, is a professor of medicine at the Johns Hopkins University School of Medicine and an investigator with the Howard Hughes Medical Institute. Siliciano (sill-ih-CAH-noh) has a joint appointment in the Department of Molecular Biology and Genetics at Johns Hopkins. Siliciano researches the mechanisms by which the human immunodeficiency virus (HIV) remains latent in the human body.[1][2]

Training and career

Siliciano had a childhood interest in chemistry fostered by his mother Ann, a professor of physiology at Elmira College,[1] and studied chemistry as an undergraduate at Princeton University. He then studied medicine and immunology at Johns Hopkins, earning both MD and PhD degrees. Siliciano continued his training in immunology with Ellis Reinherz at Harvard University, investigating the response of CD4-positive T-cells to antigens.[1]

Siliciano is a professor of medicine at the Johns Hopkins School of Medicine and a Howard Hughes Medical Institute (HHMI) investigator.

Research

The problem of HIV latency is a focus of Siliciano's research. When HIV integrates into the genome of a host cell but remains transcriptionally silent in a state known as "latency," the immune system is unable to detect and destroy the infected cell and its virus. Antiretroviral drugs are highly effective at controlling virus replication, but they also have several drawbacks. Some people experience side effects when taking these medications, and if treatment is interrupted, latent HIV can begin replicating and spreading again, often developing resistance to anti-HIV medications in the process. HIV/AIDS researchers including Siliciano have hypothesized that if all latent virus in the body could be simultaneously forced out of latency, or "reactivated," antiretroviral drugs could prevent the newly formed viruses from successfully infecting new cells, thus eradicating HIV from an infected person.[3] Several candidate drugs have been proposed, but they cause unacceptable toxicity by globally activating the patient's uninfected T cells.

In 2009, Siliciano and his laboratory published a study in the Journal of Clinical Investigation and described the in vitro use of a latency-reversing drug called 5HN (5-hydroxynaphthalene-1,4-dione). 5HN brings integrated HIV-1 out of latency but does not activate all T cells and may not be as toxic as other proposed latency-reversing compounds.

Interviewed by Bloomberg.com, Siliciano commented, "This is a way in which you could envision finding a drug that would, in conjunction with existing treatment, allow us to cure patients."[4]

Honors and awards

  • Doris Duke Charitable Foundation Distinguished Clinical Scientist Award
  • HIV DART Achievement Award in HIV Therapeutics
  • W. Barry Wood Jr. Award
  • International Association of Physicians in AIDS Care Award[1]

References

  1. ^ a b c d HHMI investigator page
  2. ^ Johns Hopkins faculty page
  3. ^ Yang, H. -C.; Xing, S.; Shan, L.; O'Connell, K.; Dinoso, J.; Shen, A.; Zhou, Y.; Shrum, C.; Han, Y.; Liu, J. O.; Zhang, H.; Margolick, J. B.; Siliciano, R. F. (2009). "Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation". The Journal of Clinical Investigation. 119 (11): 3473–3486. doi:10.1172/JCI39199. PMC 2769176. PMID 19805909.
  4. ^ "AIDS Study Flushes Out Hidden Virus, Pointing to Possible Cure" Simeon Bennet, Bloomberg. October 2nd, 2009