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Genomics and Proteomics of HIV and other Retroviruses

This research focuses on understanding the genomics and proteomics of HIV and related human retroviruses. The team has secured funding from NIH, DOD, and Snyder, and has active collaborations with GWU, NIH, and TIGR. They have published 86 peer-reviewed papers and the director leads the Genomics and Proteomics MS program.

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Genomics and Proteomics of HIV and other Retroviruses

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  1. Fatah Kashanchi, Ph.D.The George Washington University School of Medicine and Health Sciences • Genomics and Proteomics of HIV and other related human retroviruses • Resources • ~12 members • NIH, DOD, Snyder, SE funding ($2.5 M) • MALDI, LCQ • Active collaborations with GWU, NIH, TIGR • Output • 86 peer reviewed publications • Director of Genomics and Proteomics MS program bcmfxk@gwumc.edu 202-994-1781

  2. Mass Specs (MALDI-TOF and MS/MS)

  3. ) 2 + XTP + Tat (B, pNL43) (B, SF2) (B, LAI) (B, HXB + XTP + Tat Core histones Tat 20 19 CBP/p300 18 17 16 Cyclin E 15 14 Cyclin T 13 12 Ace. NFkB 11 10B 10A 9 8 7 6 5 4 3 Ace. Tat 2 1 1 2 3 4 5 6 7 8 9 10 11

  4. Latency Basal transcription (+TNF) Activated transcription (promoter proximal, non-coding region) Activated transcription (promoter distal, coding region) 3M 3M 2M 3M 3M 2M 3M 3M 3M 3M H3 H3 S10 K27 K4 K9 S10 K27 S28 K36 K9 K27 K9 S10 K27 S28 K9 a a IKK IKK a a SUV39H1/ SUV39H1/ SUV39H1/ SUV39H1/ Set 9 IKK IKK Cdk9/T Set 2 a a IKK IKK Cdk9/T HP1/ HP1/ HP1/ HP1/ G9a G9a G9a G9a CTD/Ser 5 CTD/Ser 2 P P P P P H3 H3 Env Pol Gag LTR LTR 1 20 19 2 18 3 17 4 16 5 15 6 14 7 8 13 9 12 11 10 A

  5. Cell membrane Proliferation/differentiation signals (RTK) Stress Activated JNK Cascade Ras MKK4/ MKK& Proliferation Raf (MAPKKK) Tat Differentiation MEK JNK (SAPK1) p p MAPK ERK1/ERK2 (MAPK1/MAPK2) p c-Jun s s s TCF SRF ELK-1 Transcription Factors cell type - specific responses

  6. Systems Biology • Probing genetic frameworks: What is the genomic parts list of an organism? What genes interact in concert to regulate or create a molecular interaction network? How does genetic variation influence gene expression and protein function? • Representative technologies: DNA sequencing, genotyping, large-scale gene deletion constructs; RNAi knockouts • Probing gene expression patterns: What genes are up-regulated or down-regulated in response to a genetic or environmental perturbation? What genes are expressed in what tissues under what conditions? • Representative technologies: microarrays and DNA tagging procedures • Probing DNA-protein interactions: What genes does a particular transcription factor regulate under defined experimental • conditions? • Representative technology: chromatin-immunoprecipitation and gene chips to localize binding sites (ChIP-chip) • Probing protein-protein interactions: What proteins are present in enzyme complexes, nuclear pore complexes, the • cytoskeleton? Which proteins modify other proteins in signaling cascades? • Representative technologies: two-hybrid-based interactions; affinity purification; mass spectrometry; quantitative proteomics • 5. Probing subcellular protein localization: When during development is a protein made and where in the cell does it go? • Representative technologies: cell sorting, molecular imaging based on reporter genes or antibody staining.

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