Postdoctoral and Research Fellow, National Cancer Institute
PhD, University of Washington
BA, Ohio Wesleyan University
Associate Professor, Department of Medicine, Division of Infectious Diseases
Associate Professor, Department of Microbiology and Molecular Genetics
Member, Pittsburgh Center for HIV Protein Interactions
According to UNAIDS, over 34 million people around the world are infected with HIV. The Ambrose laboratory investigates therapies for HIV prevention, treatment, and eradication with the use of basic cellular and molecular virology as well as animal models of HIV/AIDS.
New methods to prevent infection, particularly of women who may not be able to control their partners' use of condoms, are essential in curbing the epidemic. Our lab is currently testing an injectable, long-acting nanoparticle formulation of the newest FDA-approved antiretroviral drug, rilpivirine, in a macaque model. Understanding the efficacy of this treatment in reducing plasma virus and measuring the potential emergence of drug-resistant virus will help determine whether and how it can be used prophylactically to prevent HIV. In addition, Dr. Ambrose is interested in understanding the mechanisms of why some microbicides are inefficient at preventing HIV after repeated use.
Since the 1990s, combination antiretroviral therapy to treat HIV-infected individuals has saved millions of lives globally. Unfortunately, HIV drug resistance is still a problem and the Ambrose lab is studying the emergence of drug-resistant viruses in macaques treated with commonly prescribed therapy. Of particular interest is identifying the emergence and persistence of drug resistance in tissues, which cannot be easily examined in humans, and correlating drug levels in different tissues to levels of resistance. In addition, new drug targets for better therapies are needed and the Ambrose lab is involved in a collaboratory to investigate novel interactions of HIV with proteins in human cells, including primary T cells and macrophages, which can be exploited for drug development.
Although there is no cure for HIV, recent studies have given hope for new treatments to eliminate HIV-infected cells from individuals. With our animal model, the Ambrose lab is determining how virus persists in cells and how these cells are distributed in tissues throughout the body. While examining the blood in HIV-infected individuals is informative, it will not reveal infected cells in other anatomical sites that may not be accessible by some drugs. These studies will guide us in targeting therapies to these tissues for eradication, which can hopefully lead to an HIV cure.
Douglas Fischer, PhD student
Christopher Kline, lab manager
Sarah McBeth, ID fellow
Kevin Melody, PhD student
Malia Voytik, undergraduate researcher
Zhou Zhong, PhD student
Areas of Interest
Latent HIV/SIV reservoirs in infected humans/macaques during antiretroviral therapy; the early HIV-1 infection pathway of macrophages; macaque models for HIV-1 antiretrovirals and microbicides
Boltz V. F, Ambrose Z, Kearney M. F, Shao W, Kewalramani V. N, Maldarelli F, Mellors J. W. and Coffin J. M. Ultrasensitive Allele-Specific PCR Reveals Rare Preexisting Drug Resistant Variants and a Large Replicating Virus Population in Macaques Infected with RT-SHIV. J Virol. [Epub ahead of print 8/31/12] | View Abstract
Ambrose Z, Lee K, Ndjomou J, Xu H, Oztop I, Matous J, Takemura T, Unutmaz D, Engelman A, Hughes S. H, and KewalRamani V. N. Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. J Virol. 86: 4708-4714. | View Abstract
Kearney M, Spindler J, Shao W, Maldarelli F, Palmer S, Hu S. L, Lifson J. D, KewalRamani V. N, Mellors J. W, Coffin J. M, and Ambrose, Z. Genetic diversity of simian immunodeficiency virus encoding HIV-1 reverse transcriptase persists in macaques despite antiretroviral therapy. J Virol. 85: 1067-1076. | View Abstract
Jun S, Ke D, Debiec K, Zhao G, Meng X, Ambrose Z, Gibson G. A, Watkins S. C, and Zhang P. Direct visualization of HIV-1 with correlative live-cell microscopy and cryo-electron tomography. Structure. 19: 1573-1581. | View Abstract
Lee K, Ambrose Z, Martin T. D, Oztop I, Mulky A, Julias J. G, Vandegraaff N, Baumann J. G, Wang R, Yuen W, Takemura T, Shelton K, Taniuchi I, Li Y, Sodroski J, Littman D. R, Coffin J. M, Hughes S. H, Unutmaz D, Engelman A, and KewalRamani V. N. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe. 7: 221-233. | View Abstract
Ambrose Z, Compton L, Piatak M., Jr, Lu D, Alvord W. G, Lubomirski M. S, Hildreth J. E, Lifson J. D, Miller C. J, KewalRamani V. N. Incomplete protection against simian immunodeficiency virus vaginal transmission in rhesus macaques by a topical antiviral agent revealed by repeat challenges. J Virol. 82: 6591-6599. | View Abstract
Ambrose Z, Palmer S, Boltz V. F, Kearney M, Larsen K, Polacino P, Flanary L, Oswald K, Piatak M. Jr., Smedley J, Shao W, Bischofberger N, Maldarelli F, Kimata J. T, Mellors J. W, Hu S. L, Coffin J. M, Lifson J. D, and KewalRamani V. N. Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for antiretroviral therapy. J Virol. 81: 12145-12155. | View Abstract