Faculty

Nicolas Sluis-Cremer, PhD Assistant Professor of Medicine Directore of Basic Research - Division of Infectious Diseases Department of Infectious Diseases and Microbiology -(Secondary Appointment) E-mail: nps2@pitt.edu Phone: 412-648-8457 Fax: 412-648-8521 Address: Scaife Hall, Suite 817 3550 Terrace Street Pittsburgh, PA 15261

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

Research Interests

Biochemistry and cellular biology of HIV reverse transcription
Mechanisms of HIV drug resistance
Discovery of inhibitors active against drug resistant HIV-1

Recent Publications

• Harrigan, P.H., Sheen, C.-W., Gill, V.S., Wynhoven, B., Hudson, E., Lima, V.D., Lecocq, P., Aguirre, R., Poon, A.F.Y., and Sluis-Cremer, N. (2008) Silent Mutations are Selected in HIV-1 Reverse ranscriptase and Affect Enzymatic Efficiency. AIDS. In press
• Sluis-Cremer, N., and Tachedjian, G. (2008) Mechanisms by which NNRTI inhibit HIV replication. Virus Research.134: 147-156
  
• Radzio, J. and Sluis-Cremer, N. (2008) Efavirenz Accelerates HIV-1 Reverse Transcriptase Ribonuclease H Cleavage Leading to Diminished Zidovudine Excision. Mol. Pharmacol. 73: 601-606
  
• Zelina, S., Sheen, C.-W., Radzio, J., Mellors, J.W., and Sluis-Cremer, N. (2008) Mechanisms by which G333D in HIV-1 reverse transcriptase facilitates dual resistance to zidovudine (AZT) and lamivudine (3TC). Antimicrob. Agents Chemother. 52: 157-163.
  
• Yap, S., Sheen, C.-W., Fahey, J., Zanin, M., Tyssen, D., Kuiper, M., Sluis-Cremer, N., Harrigan, P.R., and Tachedjian, G. (2007) The In Vivo Mutation N348I in the Connection Domain of HIV-1 Reverse Transcriptase (RT) Confers Resistance to RT Inhibitors. PLoS Med. 4: e335
  
• Sluis-Cremer, N. (2007) Molecular Mechanisms of HIV-1 Resistance to Nucleoside and Nucleotide Reverse Transcriptase Inhibitors. Future HIV Therapy.1: 191-201
  
• Xia, Q., Radzio, J., Anderson, K.S., and Sluis-Cremer, N. (2007) Probing nonnucleoside inhibitor induced active site distortion in HIV- 1 reverse transcriptase by transient kinetic analyses. Protein Sci. 16: 1728-1737
  
• Brehm, J., Koontz, D., Pathak, V., Sluis-Cremer, N., and Mellors, J.W. (2007) Selection of Mutations in the Connection and RNase H Domains of Human Immunodeficiency Virus Type 1 Reverse Transcriptase that Increase Resistance to 3'-Azido-3'-Dideoxythymidine. J. Virol. 81: 7852-7859
  
• Parikh, U.M., Zelina, S., Sluis-Cremer, N., and Mellors, J.W. (2007) Molecular Mechanisms of Bi-Directional Antagonism between K65R and Thymidine Analog Mutations in HIV-1 Reverse Transcriptase. AIDS. 21:1405-1414
  
• Nissley, D.V., Radzio, J., Ambrose, Z., Sheen, C.-W., Hamamouch, N., Moore, K.L., Tachedjian, G., and Sluis-Cremer, N. (2007) Characterization of novel nonnucleoside reverse transcriptase (RT) inhibitor resistance mutations at residues 132 and 135 in the 51kDa subunit of HIV-1 RT. Biochem. J. 404:151-157
• Sluis-Cremer, N., Sheen, C.-W., Zelina, S., Torres, P.S., Parikh, U.M., and Mellors, J.W. (2007) Molecular Mechanism by Which the K70E Mutation in Human Immunodeficiency Virus Type 1 Reverse Transcriptase Confers Resistance to Nucleoside Reverse Transcriptase Inhibitors. Antimicrob Agents Chemother. 51:48-53
• Figueiredo A, Moore, K.L., Mak, J., Sluis-Cremer, N., de Bethune, M.P., and Tachedjian, G. (2006) Potent nonnucleoside reverse transcriptase inhibitors target HIV-1 gag-pol. PloS Pathog. 2, e11.
• Sluis-Cremer, N., Hamamouch, N., San Felix, A., Velazquez, S., Balzarini, J., and Camarasa, M.J. (2006) Structure-activity relationships of [2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]- 3'-spiro-5' '-(4' '-amino-1' ',2' '-oxathiole-2' ',2' '-dioxide)thymine derivatives as inhibitors of HIV-1 reverse transcriptase dimerization. J Med Chem. 49: 4834-41
• Sluis-Cremer, N., and Kempner, E.S. (2006) Radiation target analyses of DNA template/primer complexes. Biophys. J. 90: L61-63
• Sluis-Cremer N, Arion D, Parikh U, Koontz D, Schinazi RF, Mellors JW, Parniak MA. (2005) The 3'-azido group is not the primary determinant of AZT responsible for the excision phenotype of AZT-resistant HIV-1. J Biol Chem. 280: 29047-52