Training Technologies Used:
Molecular and cellular virology
Single-genome sequencing
Live-cell and super resolution imaging
Possible Rotation Projects:
Bioinformatics of HIV drug resistance evolution
Analysis of live-cell and super-resolution imaging of HIV infection of cells.
- B.A., Zoology and Pre-Medicine, Ohio Wesleyan University, 1994
- Ph.D., Pathobiology, University of Washington School of Public Health, 2001
- Post-doctoral and Research Fellow, National Cancer Institute, 2001-2007
Medrano JM, Sunny PS, Diedrich CR, Maiello P, Kline C, Rutledge T, Klein E, Mattila J, Das J, Ambrose Z, Lin PL. SIV infection disrupts the spatial cellular and communication networks of pulmonary granulomas during SIV/Mtb co-infection, bioRxiv 2026, 2026.04.24.720743. PMC13131680
Fischer HL, Shanmugapriya S, Kline C, Duprex WP, McCarthy KR, Watkins SC, Conway JF, Ambrose Z. Deletion of the Envelope gene attenuates SARS-CoV-2 infection by altered Spike localization and increased cell-to-cell transmission, bioRxiv 2025, 2025.05.20.655126. PMC12140015
Ingram Z, Kline C, Hughson AK, Singh PK, Fischer HL, Radhakrishnan R, Sowd GA, Dos Santos NFB, Ganser-Pornillos BK, Watkins SC, Kane M, Engelman AN, Ambrose Z. Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration, mBio 2025, 16(4):e0016925. PMC11980554
Tisthammer K, Kline C, Rutledge T, Diedrich C, Ita S, Lin PL, Ambrose Z, Pennings PS. SIV evolutionary dynamics in cynomolgus macaques during SIV-Mycobacterium tuberculosis co-infection, Viruses 2021, 14(1):48. PMC8778162
Zhong Z, Ning J, Boggs EA, Jang S, Wallace C, Telmer C, Bruchez MP, Ahn J, Engelman AN, Zhang P, Watkins SC, Ambrose Z. Cytoplasmic CPSF6 regulates HIV-1 capsid trafficking and infection in a cyclophilin A-dependent manner, mBio 2021, 12:e3142-20. PMC8092277
Xu C*, Fischer DK*, Rankovic S*, Li W, Dick R, Runge B, Ahn J, Aiken C, Polenova T, Engelman AN, Ambrose Z, Rousso I, Perilla JR. Permeability of the HIV-1 capsid to metabolites modulates viral DNA synthesis, PLoS Biol 2020, 18(12):e3001015. PMC7775124
Melody K, Roy CN, Kline C, Cottrell ML, Evans D, Shutt K, Pennings PS, Keele BF, Bility M, Kashuba ADM, Ambrose Z. Long-acting rilpivirine (RPV LA) pre-exposure prophylaxis does not inhibit vaginal transmission of RPV-resistant HIV-1 nor select for high frequency drug resistance in humanized mice. J Virol 2020, 94(8):e01912-19. PMC7108851
Feder AF, Kline C, Polacino P, Cottrell M, Kashuba ADM, Keele BF, Hu SL, Petrov DA, Pennings PS, Ambrose Z. A spatio-temporal assessment of simian/human immunodeficiency virus (SHIV) evolution reveals a highly dynamic process within the host. PLoS Pathog 2017, 13(5):e1006358. PMC5444849
Feder AF, Kline C, Polacino P, Cottrell M, Kashuba ADM, Keele BF, Hu SL, Petrov DA, Pennings PS, Ambrose Z. A spatio-temporal assessment of simian/human immunodeficiency virus (SHIV) evolution reveals a highly dynamic process within the host. PLoS Pathog 2017, 13(5):e1006358. PMC5444849
Lee K, Ambrose Z, Martin TD, Oztop I, Mulky A, Julias JG, Vandegraaff N, Baumann JG, Wang R, Yuen W, Takemura T, Shelton K, Taniuchi I, Li Y, Sodroski J, Littman DR, Coffin JM, Hughes SH, Unutmaz D, Engelman A, KewalRamani VN. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 2010, 7:221-33. PMC2481689
The Ambrose Lab is a collaborative team of scientists studying HIV-1 and coronavirus pathogenesis and therapeutics. We use molecular and cellular virology together with live cell and super-resolution microscopy to understand how HIV-1 and other retroviruses interact with intracellular host proteins during replication. For example, as the HIV-1 capsid traffics rapidly from the cell periphery into the nucleus, it shields the formation of viral DNA during reverse transcription from innate immunity. We are developing novel methods to visualize and measure capsid dissociation as well as sequential binding of multiple host proteins to HIV-1 capsids/pre-integration complexes during infection, which can dictate whether successful viral infection occurs or if innate immunity restricts infection. These techniques can likely be beneficial in studying other pathogens and cell biology mechanisms. We are also studying post-entry replication of SARS-CoV-2 and novel inhibitor mechanisms.
We use humanized mice to address clinically relevant HIV-1 questions that cannot be answered with cell culture alone or that cannot be ethically performed in humans. We are studying the evolution, transmission, and persistence of lenacapavir-resistant variants. Lenacapavir is a recently FDA-approved first-in-class HIV-1 capsid inhibitor that targets the capsid binding site of some host cell proteins. We do not currently understand the evolution of lenacapavir resistance, which involves a complex pattern of mutations. Furthermore, we do not know whether lenacapavir-resistant isolates can be transmitted between individuals, particularly via a mucosal route, and how they persist. We also are developing animal models to understand the dynamics of pathogens that commonly cause co-infection with HIV-1, leading to worse clinical outcomes even during antiretroviral therapy.
