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Department of Medicine

Department of Medicine

 Division of Infectious Diseases

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photo Nicolas Sluis-Cremer, PhD

Director of Laboratory Research, Division of Infectious Diseases

Email: nps2@pitt.edu

Phone: 412-648-8457

Contact
Office: Scaife Hall, Suite 817
3550 Terrace Street
Pittsburgh, PA 15261
 
Phone: 412-648-8457
Fax: 412-648-8521
E-mail: nps2@pitt.edu
Education and Training
Education
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
Training
Postdoctoral, McGill University AIDS Center, Canada, 2001
Research Interest
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.
Educational Interest
Dr. Sluis-Cremer is involved in Ph.D graduate education in the School of Medicine and the Graduate School of Public Health.
Publications
For my complete bibliography, Click Here.
Selected 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.
Sponsored Research/Activities
Title: The "Kick" Revisited in the "Kick and Kill" Strategy
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R21 AI119117
Start Year: 2016
End Year: 2018
Title: Novel Mechanisms of HIV Resistance to RTIs
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R01 AI081571
Start Year: 2015
End Year: 2019
Title: Conformational Dynamics and Inhibitor Responses of HIV-1 RT Rnase H in Solution
Role: Principal Investigator
Funding Agency: National Institute of General Medical Science
Grant Number: R01 GM105401
Start Year: 2015
End Year: 2016
Title: NNRT1 Induced Conformational Changes in HIV 1 RT
Role: Principal Investigator
Funding Agency: National Institute of General Medical Science
Grant Number: R01 GM068406
Start Year: 2014
End Year: 2018
Title: Pittsburgh Center for HIV Protein Interactions (PCHPI)
Role: Principal Investigator
Funding Agency: National Institute of General Medical Science
Grant Number: P50 GM082251
Start Year: 2014
End Year: 2015
Title: Preclinical Development of RS-788
Role: Principal Investigator
Funding Agency: Brigham and Women's Hospital, Inc./National Institute of Allergy & Infectious Diseases
Grant Number: UM1 AI068636
Start Year: 2013
End Year: 2014
Title: Novel Mechanisms of HIV Resistance to RTIs
Role: Principal Investigator
Funding Agency: National Institute of Allergy & Infectious Diseases
Grant Number: R01 AI085171
Start Year: 2009
End Year: 2014
Title: NNRTI Induced Conformational Changes in HIV-1 RT
Role: Principal Investigator
Funding Agency: National Institute of General Medical Science
Grant Number: R01 GM068406
Start Year: 2009
End Year: 2014
Notable Achievements
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