Nicolas Sluis-Cremer, PhD

  • Professor of Medicine
  • Associate Chief of Research and Outreach
  • Director of Laboratory Research, Division of Infectious Diseases
Academic Interests

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.

    Education & Training

  • 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
Recent Publications

Schauer GD, Huber K, Leuba S, Sluis-Cremer N. Mechanism of allosteric inhibition of HIV-1 reverse transcriptase revealed by single-molecule and ensemble fluorescence. Nucleic Acids Res. 2015; 42(18): 11687-96.

Doyon G, Zerbato J, Mellors JW, Sluis-Cremer N. Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog (PTEN). AIDS. 2013; 27(2): F7-F11.

Brumme CJ, Huber KD, Dong W, Poon AF, Harrigan PR, Sluis-Cremer N. Replication fitness of multiple NNRTI-resistant HIV-1 variants in the presence of etravirine measured by 454 deep sequencing. J Virol. 2013; 87(15): 8805-7.

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; 40: 381-90.

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-1 from latently infected cells. J. Biol Chem. 2011; 286(25): 22211-8.

    Honors and Awards
  • 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
Research Grants

Title: University of Pittsburgh MACS-WIHS CCS
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: U01 HL146208
Start Year: 2019
End Year: 2026