Robert F. Siliciano
Encyclopedia
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
Howard Hughes Medical Institute
Howard Hughes Medical Institute is a United States non-profit medical research organization based in Chevy Chase, Maryland. It was founded by the American businessman Howard Hughes in 1953. It is one of the largest private funding organizations for biological and medical research in the United...

. 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.

Training and career

Siliciano had a childhood interest in chemistry fostered by his mother Ann, a professor of physiology at Elmira College
Elmira College
Elmira College is a coeducational private liberal arts college located in Elmira, in New York State's Southern Tier region.The college is noted as the oldest college still in existence which granted degrees to women that were the equivalent of those given to men...

, and studied chemistry as an undergraduate at Princeton University
Princeton University
Princeton University is a private research university located in Princeton, New Jersey, United States. The school is one of the eight universities of the Ivy League, and is one of the nine Colonial Colleges founded before the American Revolution....

. He then studied medicine and immunology
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...

 at Johns Hopkins, earning both MD
Doctor of Medicine
Doctor of Medicine is a doctoral degree for physicians. The degree is granted by medical schools...

 and PhD
PHD
PHD may refer to:*Ph.D., a doctorate of philosophy*Ph.D. , a 1980s British group*PHD finger, a protein sequence*PHD Mountain Software, an outdoor clothing and equipment company*PhD Docbook renderer, an XML renderer...

. Siliciano continued his training in immunology with Ellis Reinherz at Harvard University
Harvard University
Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...

, investigating the response of CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...

-positive T-cells to antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s.

Siliciano is a professor of medicine at the Johns Hopkins School of Medicine
Johns Hopkins School of Medicine
The Johns Hopkins School of Medicine , located in Baltimore, Maryland, U.S., is the academic medical teaching and research arm of Johns Hopkins University. Hopkins has consistently been the nation's number one medical school in the amount of competitive research grants awarded by the National...

 and a Howard Hughes Medical Institute (HHMI) investigator.

Research

The problem of HIV latency is a focus of Siliciano's research. When HIV integrates
Pre-integration complex
The pre-integration complex is a nucleoprotein complex of viral genetic material and associated viral and host proteins. The PIC forms after uncoating of a viral particle after entry into the host cell...

 into the genome of a host cell but remains transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

ally silent in a state known as "latency," the immune system is unable to detect and destroy the infected cell and its virus. Antiretroviral drug
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...

s are highly effective at controlling virus replication, but they also have several drawbacks. Some people experience side effects
Side Effects
Side Effects is an anthology of 17 comical short stories written by Woody Allen between 1975 and 1980, all but one of which were previously published in, variously, The New Republic, The New York Times, The New Yorker, and The Kenyon Review. It includes Allen's 1978 O...

 when taking these medications, and if treatment is interrupted, latent HIV can begin replicating and spreading again, often developing resistance to anti-HIV medications
Drug resistance
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...

 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. Several candidate drugs have been proposed, but they cause unacceptable toxicity by globally activating the patient's uninfected T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s.

In 2009, Siliciano and his laboratory published a study in the Journal of Clinical Investigation
Journal of Clinical Investigation
The Journal of Clinical Investigation is a biomedical journal, with a 2010 impact factor of 14.152. The journal makes its research articles — including access to articles back to 1924 — freely available online....

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."

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
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