Dr. D’Orso received his B.S. and Master in Biological Sciences, from the National University of Mar del Plata (Buenos Aires, Argentina) in 1998. Dr. D’Orso then obtained his Ph.D. in Biochemistry and Molecular Biology from the National University of Buenos Aires (Argentina) in 2003 under the tutelage of the U.S. National Academy Member Dr. Alberto C. Frasch. He continued his training as a post-doctoral fellow with Dr. Alan D. Frankel at the Department of Biochemistry and Biophysics at the University of California, San Francisco, during which time he was supported by fellowships from the Fundación Antorchas (Argentina), Human Frontier Science Program and amfAR. During his postdoctoral position, Dr. D’Orso elucidated key features about the mechanisms of HIV transcriptional regulation. Following receipt of a NIH Pathway to Independence Award (K99/R00) from the NIAID in 2009, Dr. D’Orso began his independent career in November 2010. The major theme of his work is to characterize the mechanisms of HIV transcriptional regulation, and the molecular and structural basis of cellular reprogramming by viral transcription factors. He uses a wide-range of approaches (genetics, protein biochemistry, functional genomics and virology) to identify and characterize molecular mechanisms of HIV-host interplay and transcriptional control. These combined strategies led him to discover a novel pathogenic mechanism by which the viral Tat protein assembles with host co-factors to active the switch between transcription initiation into elongation at the HIV promoter. Tat assembles a multi- host co-factor protein-RNA complex essential for viral transcription and replication, thus making them ideal targets for therapeutic intervention. His current work is focused on using cell biological, biochemical and genetic studies to elaborate the contribution of these host co-factors to the establishment of latency and efforts for HIV eradication. Dr. D’Orso’s research program is supported by grants from the National Institutes of Health, The Welch Foundation and an Institutional grant from the American Cancer Society.
- National University of Mar Del Plata - Argentina (1998)
- Graduate School
- National University of San Martin - Argentina (2003), Molecular Biology
- Chromatin biology
- Host-pathogen interactions
- Protein-RNA complexes
- Transcriptional regulation
- HIV Tat controls RNA Polymerase II and the epigenetic landscape to transcriptionally reprogram target immune cells.
- Reeder JE, Kwak YT, McNamara RP, Forst CV, D'Orso I Elife 2015 Oct 4
- PPM1G binds 7SK RNA and Hexim1 to block P-TEFb assembly into the 7SK snRNP and sustain transcription elongation.
- Gudipaty SA, McNamara RP, Morton EL, D'Orso I Mol. Cell. Biol. 2015 Aug
- Transcription factors mediate the enzymatic disassembly of promoter-bound 7SK snRNP to locally recruit P-TEFb for transcription elongation.
- McNamara RP, McCann JL, Gudipaty SA, D'Orso I Cell Rep 2013 Dec 5 5 1256-68
- Transition Step during Assembly of HIV Tat:P-TEFb Transcription Complexes and Transfer to TAR RNA.
- D'Orso I, Jang GM, Pastuszak AW, Faust TB, Quezada E, Booth DS, Frankel AD Mol. Cell. Biol. 2012 Dec 32 23 4780-93
- Transcription control by long non-coding RNAs.
- Faust T, Frankel A, D'Orso I Transcription 2012 Mar 3 2
- RNA-mediated displacement of an inhibitory snRNP complex activates transcription elongation.
- D'Orso I, Frankel AD Nat. Struct. Mol. Biol. 2010 Jul 17 7 815-21
- Mechanisms of eukaryotic transcription: A meeting report: August 27-31, 2013, CSHL, Cold Spring Harbor, NY.
- D'Orso I Transcription 2013 Nov 4 5
- Global landscape of HIV-human protein complexes.
- Jäger S, Cimermancic P, Gulbahce N, Johnson JR, McGovern KE, Clarke SC, Shales M, Mercenne G, Pache L, Li K, Hernandez H, Jang GM, Roth SL, Akiva E, Marlett J, Stephens M, D'Orso I, Fernandes J, Fahey M, Mahon C, O'Donoghue AJ, Todorovic A, Morris JH, Maltby DA, Alber T, Cagney G, Bushman FD, Young JA, Chanda SK, Sundquist WI, Kortemme T, Hernandez RD, Craik CS, Burlingame A, Sali A, Frankel AD, Krogan NJ Nature 2012 Jan 481 7381 365-70
- Purification and characterization of HIV-human protein complexes.
- Jäger S, Gulbahce N, Cimermancic P, Kane J, He N, Chou S, D'Orso I, Fernandes J, Jang G, Frankel AD, Alber T, Zhou Q, Krogan NJ Methods 2011 Jan 53 1 13-9
- HIV-1 Tat: Its Dependence on Host Factors is Crystal Clear.
- D'Orso I, Frankel AD Viruses 2010 Oct 2 10 2226-2234
Honors & Awards
- The Welch Foundation
- NIH/NIAID K99/R00 Pathway to Independence Award, USA
- amfAR Postdoctoral Fellow
Inaugural Mathilde Krim Fellowship to support bright young scientist for AIDS Research (2008)
- Human Frontier Science Program (HFSP) Postdoctoral Fellow
- Sixth Young Talent Prize - Amersham-Pharmacia, Brazil
- Research in Health Science prize, Argentina