Bharat Ramratnam, A.B., M.D.
Associate Professor of Medicine
Department of Medicine
Work: +1 401-444-5219
Our focus is on defining the key cellular components that impact the replication of viruses such as HIV-1, herpes simplex virus (HSV) one and two, influenza, and hepatitis B/C. We use a variety of genetic and proteonomic techniques to identify host factors that impact viral replication, some of which may constitute novel targets for pharmacotherapy.
BiographyDr. Ramratnam completed undergraduate and medical education at Brown University. Following residency and chief residency at Brown, he completed a postdoctoral fellowship at The Aaron Diamond AIDS Research Center, The Rockefeller University in the Clinical Scholars Program and is now the head of the Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Brown Medical School. He also directs the COBRE Center for Cancer Research Development at Rhode Island Hospital and is an Attending Physician at Miriam and Rhode Island Hospitals.
Research DescriptionOur focus is on defining the key cellular components that impact the replication of viruses such as HIV-1, herpes simplex virus (HSV) one and two, influenza, and hepatitis B/C. We use a variety of genetic and proteonomic techniques to identify host factors that impact viral replication, some of which may constitute novel targets for pharmacotherapy. Our laboratory is using RNA interference as a molecular tool and we have completed the synthesis of RNAi libraries to allow for rapid screening of the "virus-host" interactome.
Grants and Awards1994 American College of Physicians Finalist, Abstract Competition, Rhode Island Chapter.
1994 American Federation for Clinical Research Trainee Investigator Award for Excellence in Clinical Research
1995 American College of Physicians Finalist, Abstract Competition, Rhode Island Chapter
1994-1997 American Federation for Clinical Research Trainee Investigator Award for Excellence in Clinical Research
1996 American College of Physicians Finalist, Abstract Competition, Rhode Island Chapter
2000-2002 Daland Fellowship in Clinical Investigation, the American Philosophical Society
2000-2005 National Institutes of Health, Career Development Award
2001-2006 Clinical Scientist Development Award, Doris Duke Charitable Foundation
2002 Charles Culpepper Biomedical Pilot Initiative, Rockefeller Brothers Fund
2003 Junior Physician Scientist Award, American Federation for Medical Research
2005 Independent Investigator Award, Centers of Biomedical Research Excellence (COBRE) Center for Cancer Research Development, Rhode Island Hospital
Affiliations2003-present Ad hoc reviewer of investigator initiated grants for:
Medical Research Council of South Africa (2005)
National Institutes of Health (NIH) Microbicide Innovation Program (2006)
NIH AIDS Discovery and Development of Therapeutics (ADDT) study section (2006)
Lifespan/Brown/Tufts Center for AIDS Research (CFAR) pilot project applications (2005)
Gene therapy programs, The Netherlands (2003-present)
2004 Reviewer, World Health Organization (WHO) Guidelines for HIV Diagnosis and Monitoring of Antiretroviral Therapy
2000-present Referee for the Lancet, Journal of Infectious Diseases, Nucleic Acids Research, Journal of AIDS, Molecular Therapy
Funded Research1. The Impact of Multidrug Resistant Proteins on HIV Treatment.
Clinical Scientist Development Award, Doris Duke Charitable Foundation.
PI: Bharat Ramratnam.
7-01-01 to 6-30-06, 25% effort --$100,000/yr
This project will determine whether cells harboring multidrug proteins such as P-glycoprotein and multidrug resistant proteins 4/5 serve as reservoirs of HIV replication during HAART.
2. Novel HIV-1 microbicides
National Institutes of Health (NIH) 1R21AI067074-01
PI: Bharat Ramratnam
7-01-05 to 06-30-07, 5% effort--$125,000/yr
We will determine the efficacy of mucosal anti-CCR5 siRNA in preventing vaginal/rectal transmission of SIV in a macaque model.
3. CV-N Secreting Lactobacilli and Retrocyclin Microbicides.
PI: Phalguni Gupta
7-10-05 to 6-30-09
Project 1 PI: Bharat Ramratnam, 15% effort.--$150,000/yr
The goal of this cooperative agreement is to engineer lactobacilli (LAB) to secrete anti-HIV-1 compounds and to determine the in vivo mucosal retention kinetics of bioengineered LAB in pigtail macaques. We will also quantify the kinetics if secretion of chosen antiviral compounds and their microbicidal potential in vaginal/rectal virus challenge experiments.
4. Using RNAi to Dissect Stem Cell Potential.
PI: Peter Quesenberry
9-30-03 to 6-30-08
Project 3 PI: Bharat Ramratnam, 15% effort--$40,000/yr
The goal of this proposal is to utilize RNA interference to systematically map the effect of transcription factor knockdown on the cellular fate of progenitor stem cells in a murine model.
5. Overcoming HIV-1 resistance to RNA interference
PI: Bharat Ramratnam
08-15-05 to 07-31-10, 30% effort--$250,000/yr
The goal of this project is to use a murine xenotransplant model of HIV-1 transmission and determine the efficacy of RNAi in preventing HIV-1 transmission.
6. Retrovirology Core, Lifespan/Brown/Tufts Center for AIDS Research (CFAR)
PI: CCJ Carpenter, Core Co-PI: Bharat Ramratnam
09-01-88 to 06-30-07, 10% effort--$108,000/yr
The goal is to provide basic science services to CFAR investigators.
7. Creation and testing of the advanced system for lentivector-mediated transduction of hematopoietic stem cells and expression of anti-HIV-1 shRNAs
United States Civilian Research and Development Foundation for the Independent States of the Former Soviet Union
American PI: B. Ramratnam
I offer lectures in the medical school on retrovirology and the mechanics of the genome including DNA and RNA replication and protein synthesis.
- Integrated Medical Sciences I (BI0364)
- Medical Microbiology (BI0158)
- 28. Zhang Y, Cristafaro P, Silbermann R, Pusch O, Monfils P, Hovanesian V, Boden D, Resnick M, Moss SF, Ramratnam B. Engineering mucosal RNAi in vivo. In press Molecular Therapy. (IN PRESS)
- 27. Pusch O, Boden D, Hannify S, Lee F, Tucker L, Wells JM, Boyd MR, Ramratnam B, Engineering Lactic Acid Bacteria to secrete the virucide cyanovirin. J Acquir Immune Defic Syndr. 40(5):512-20, 2005 (2005)
- 25. Newstein M, Losikoff P, Caliendo A, Ingersoll J, Kurpewski J, Hanley D, Cerezo J, Ramratnam B, Cu-Uvin S. Prevalence and persistence of nonnucleoside reverse transcriptase inhibitor mutations in the female genital tract. J Acquir Immune Defic Syndr 38(3):364-6, 2005. (2005)
- 26. Balakrishnan P, Kumarasamy N, Solomon S, Vidya S, Kantor R, Mayer K, Newstein M, Thyagarajan SP, Katzenstein D, Ramratnam B. HIV-1 genotypic variation in an antiretroviral treatment naïve population in South India. AIDS Res Hum Retroviruses 21(4):301-5, 2005. (2005)
- 24. Pusch O, Boden D, Silbermann R, Lee F, Tucker L, Ramratnam B. Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins. Nucleic Acids Research 32: 1154-58, 2004. (2004)
- 22. Pusch O, Boden D, Silbermann R, Lee F, Tucker L, Ramratnam B. Efficient gene transfer of HIV-1 specific short hairpin RNA into human lymphocytic cells using recombinant adeno-associated virus (rAAV) vectors. Molecular Therapy 9:396-402, 2004. (2004)
- 23. Ramratnam B, Ribeoro R, He T, Chung C, Simon V, Vanderhoeven J, Hurley A, Zhang L, Perelson AS, Ho DD, Markowitz M. Intensification of antiretroviral therapy accelerates the decay of the HIV-1 latent reservoir and decreases but does not eliminate ongoing virus replication. JAIDS 35: 33-7, 2004. (2004)
- 21. Boden D, Pusch O, Lee F, Tucker L, Ramratnam B. HIV-1 escape from RNA interference. Journal of Virology 77: 11531-11535, 2003. (2003)
- 20. Boden D, Pusch O, Lee F, Tucker L, Shank P, Ramratnam B. Nucleotide sequence homology requirements of HIV-1 specific shRNA. Nucleic Acids Research 31:6444-9, 2003. (2003)
- 19. Boden D, Pusch O, Lee F, Tucker L, Shank PR, Ramratnam B. Promoter choice affects the potency of HIV-1 specific RNA interference. Nucleic Acids Research 31:5033-8, 2003. (2003)
- 18. Simon V, Vanderhoeven J, Hurley A, Ramratnam B, Louie M, Dawson K, Parkin N, Boden D, Markowitz M. (2002) Evolving patterns of HIV-1 resistance to antiretroviral agents in newly infected individuals. AIDS 11:1511-9, 2002. (2002)
- 17. Ortiz GM, Hu J, Goldwitz JA, Chandwani R, Larsson M, Bonhoeffer S, Ramratnam, B, Zhang L, Markowitz M, Nixon DF. (2002) Residual viral replication during antiretroviral therapy boosts human immunodeficiency virus type 1-specific CD8+ T-cell responses in subjects treated early after infection. J Virol 76:411-5, 2002. (2002)
- 16. Mohri, H., Perelson, A.S., Tung, K., Ribeiro, R., Ramratnam, B., Markowitz, M., Kost, R., Hurley, A., Weinburger, L., Cesar, D., Hellerstein, M.K., Ho, D.D. (2001) Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med.194:1277-87. (2001)
- 14. Ramratnam B, Mittler JE, Zhang L, Boden D, Hurley A, Fang F, Macken CA, Perelson AS, Markowitz M, Ho DD. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged antiretroviral therapy. Nat Med 6: 82-85, 2000. (2000)
- 15. Zhang L, Chung C, Hu BS, He T, Guo Y, Kim AJ, Skulsky E, Jin X, Hurley A, Ramratnam B, Markowitz M, Ho DD. (2000) Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy. J Clin Invest 106: 839-45, 2000. (2000)
- 13. Ramratnam B, Bonhoeffer S, Binley J, Hurley A, Zhang L, Mittler JE, Markowitz M, Moore JP, Perelson AS, Ho DD. Rapid production and clearance of HIV-1 and hepatitis C virus particles in infected individuals as defined by large volume plasma aphaeresis. Lancet 354: 1782-5, 1999. (1999)
- 12. Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. (1999) Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 340: 1605-13, 1999. (1999)
- 11. Larsson M, Jin X, Ramratnam B, Ogg GS, Engelmayer J, Demoitie MA, McMichael AJ, Cox WI, Steinman RM, Nixon D, Bhardwaj N. A recombinant vaccinia virus based ELISPOT assay detects high frequencies of pol-specific CD8+ cells in HIV-1 positive individuals. AIDS 13:767-7, 1999. (1999)
- 10. Ahmed A, Aggarwal M, Chiu R, Ramratnam B, Rinaldi M, Flanigan TP. A fatal case of Rhodotorula meningitis in AIDS. Med Health RI 81: 22-3, 1998. (1998)
- 8. Rich JD, Ramratnam B, Chiang B, Tashima K. (1997) Management of indinavir associated nephrolithiasis. J Urology 158: 2228, 1997. (1997)
- 7. Grube H, Ramratnam B, Flanigan TP. Resolution of AIDS associated cryptosporidiosis after treatment with indinavir. Amer J Gastroen 92:726, 1997. (1997)
- 6. Rich JD, Ramratnam B, Flanigan TP. Triple combination antiretroviral prophylaxis of needle stick exposure to HIV. Infect Control Hosp Epidemiol 18:161,1997. (1997)
- 5. Ramratnam B, Kelly G, Mega A, Schiffman FJ. (1997) Determinants of case selection at morning report. J Gen Intern Med 12: 263-6, 1996. (1997)
- 9. Ramratnam B, Tsoulfas G, Parikh A, Vigilante K, Flanigan TP. Former prisoners' views on mandatory HIV testing in prison. J Correctional Health Care 4:155-64, 1997. (1997)
- 4. Ramratnam B, Parameswaran J, Elliot B, Newstein M, Schiffman FJ, Rich JD, Flanigan TP. Short course dexamethasone for thrombocytopenia in AIDS. Amer J Med 100:117-8, 1996. (1996)
- 3. Flanigan, TP, Ramratnam B, Graeber C, Hellinger J, Smith D, Wheeler D, Hawley, P, Heath-Chiozzi M, Ward D, Brummitt C, Turner J. (1996) Prospective trial of paramomycin for cryptosporidiosis in AIDS. Amer J Med 100: 370-2, 1996. (1996)
- 2. Ramratnam B, Gollerkeri A, Martens P, Schiffman FJ, Parameswaran J. A study of cross coverage calls. J Gen Intern Med 11: 89, 1996. (1996)
- 1. Ramratnam B, Gollerkeri A, Schiffman FJ, Rintels P, Flanigan TP. Management of persistent B19 parvovirus infection in AIDS. Br J Haematol 91: 90-2, 1995. (1995)