Dr. Sluis-Cremer's laboratory uses a multi-disciplinary approach that includes biophysics, biochemistry, virology, and analysis of clinical samples to gain insight into the mechanisms of action of antiretroviral drugs; antiviral and antimicrobial drug resistance; and understanding how HIV-1 persists in infected individuals despite potent antiretroviral therapy. His lab uses state-of-the-art biophysical methods, including transient kinetic and single-molecule fluorescence approaches, to define how small molecules affect retroviral enzyme function, the intramolecular protein conformational dynamics, and the intermolecular enzyme-substrate interactions. Dr. Sluis-Cremer's HIV-1 resistance research focuses on identifying drug resistance mutations that are selected in infected-individuals failing therapy, defining the mechanisms by which these mutations decrease drug susceptibility, and predicting how acquired or transmitted drug resistance mutations impact treatment options. His lab also studies antibiotic resistance and is exploring novel therapeutic approaches to reverse fosfomycin resistance. In regard to HIV-1 persistence, the lab focuses on characterizing the latent pool of HIV-1 infection that resides in resting CD4+ T cells, in particular the naive and central memory subsets, using novel primary cell models of HIV-1 latency and by studying purified subsets of the resting CD4+ T cell population from HIV-infected individuals on suppressive antiretroviral therapy.
- BSc, University of the Witwatersrand, South Africa, 1994
- BSc (Hons), University of the Witwatersrand, South Africa, 1995
- PhD, University of the Witwatersrand, South Africa, 1997
- Postdoctoral, McGill University AIDS Center, Canada, 2001
Education & Training
Vázquez Rivera A, Donald H, Alaoui-El-Azher M, Skoko JJ, Lazo JS, Parniak MA, Johnston PA, Sluis-Cremer N. Discovery of Benzisothiazolone Derivatives as Bifunctional Inhibitors of HIV-1 Reverse Transcriptase DNA Polymerase and Ribonuclease H Activities. Biomolecules. 2024 Jul 9;14(7):819. PMID: 39062532.
Zerbato JM, McMahon DK, Sobolewski MD, Mellors JW, Sluis-Cremer N. Naive CD4+ T Cells Harbor a Large Inducible Reservoir of Latent, Replication-competent Human Immunodeficiency Virus Type 1. Clin Infect Dis. 2019 Nov 13;69(11):1919-1925. PMID: 30753360.
Tomich AD, Klontz EH, Deredge D, Barnard JP, McElheny CL, Eshbach ML, Weisz OA, Wintrode P, Doi Y, Sundberg EJ, Sluis-Cremer N. Small-Molecule Inhibitor of FosA Expands Fosfomycin Activity to Multidrug-Resistant Gram-Negative Pathogens. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e01524-18. PMID: 30642934.
Vargas B, Giacobbi NS, Sanyal A, Venkatachari NJ, Han F, Gupta P, Sluis-Cremer N. Inhibitors of Signaling Pathways That Block Reversal of HIV-1 Latency. Antimicrob Agents Chemother. 2019 Jan 29;63(2):e01744-18. PMID: 30455231.
Zerbato JM, Serrao E, Lenzi G, Kim B, Ambrose Z, Watkins SC, Engelman AN, Sluis-Cremer N. Establishment and Reversal of HIV-1 Latency in Naive and Central Memory CD4+ T Cells In Vitro. J Virol. 2016 Aug 26;90(18):8059-73. PMID: 27356901.
Doyon G, Sobolewski MD, Huber K, McMahon D, Mellors JW, Sluis-Cremer N. Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1. PLoS One. 2014 Jan 29;9(1):e84964. PMID: 24489654.
Doyon G, Zerbato J, Mellors JW, Sluis-Cremer N. Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS. 2013 Jan 14;27(2):F7-F11. PMID: 22739395.
Brumme CJ, Huber KD, Dong W, Poon AF, Harrigan PR, Sluis-Cremer N. Replication fitness of multiple nonnucleoside reverse transcriptase-resistant HIV-1 variants in the presence of etravirine measured by 454 deep sequencing. J Virol. 2013 Aug;87(15):8805-7. PMID: 23720723.
Huber K, Doyon G, Plaks J, Fyne E, Mellors JW, Sluis-Cremer N. Inhibitors of histone deacetylases: correlation between isoform specificity and reactivation of HIV type 1 (HIV-1) from latently infected cells. J Biol Chem. 2011 Jun 24;286(25):22211-8. PMID: 21531716.
Herman BD, Schinazi RF, Zhang HW, Nettles JH, Stanton R, Detorio M, Obikhod A, Pradère U, Coats SJ, Mellors JW, Sluis-Cremer N. Substrate mimicry: HIV-1 reverse transcriptase recognizes 6-modified-3'-azido-2',3'-dideoxyguanosine-5'-triphosphates as adenosine analogs. Nucleic Acids Res. 2012 Jan;40(1):381-90. PMID: 21914723.
- Carnegie-WITS Diaspora Fellow
- Associate Editor, BMC Biochemistry
- Editorial Board Member, Antimicrobial Agents and Chenotherapy, PLoS One, Journal of Antivirals and Antiretrovirals, Clinical Research in Infectious Diseases
- NIH Study Section Member, HIV/AIDS Innovative Research Applications (ZRG1 AARR-E), AIDS Predoctoral and Postdoctoral Fellowships (AARRC 22)
- Scientific Committee Member, HIV DART: Frontiers In Drug Development for Antiretroviral Therapies
- Editorial Board Member, PLoS One
R01 AI197205, Time resolved structural analyses of β-lactam/β-lactam inhibitor binding to AmpC, MPI, 2026-2031.
R01 AI175067, "On the Fly" Time Resolved Cryo-EM Studies of Intermediate HIV-1 RT Transition States, MPI, 2022-2027.
R01AI162615, Elucidating the role of B cell mediated trans infection in the establishment of the latent HIV-1 reservoir, PI, 2022-2026.
U01 HL146208, University of Pittsburgh MACS-WIHS CCS, Co-Investigator, 2019-2026.
