Tyagi Research

Tyagi M, Rusnati M, Presta M, Giacca M; Internalization of HIV-1 Tat Requires Cell Surface Heparan Sulfate Proteoglycans. J Biol Chem. 2001 Feb 2;276(5):3254-3261.

I identified heparin sulphate proteoglycans (HSPGs) as the cellular receptor for HIV-1 Tat protein. The resultant article from that study has already been cited more than 1000 times and has become a reference point for innumerable cellular translocation studies of various proteins. (Cited by more than 1000 articles)

Zicari S, Sharma AL, Sahu G, Dubrovsky L, Sun L, Yue H, Jada T, Ochem A, Simon G, Bukrinsky M, Tyagi M; DNA dependent protein kinase (DNA-PK) enhances HIV transcription by promoting RNA polymerase II activity and recruitment of transcription machinery at HIV LTR.; Oncotarget. 2020 Feb 18;11(7):699-726. doi: 10.18632/oncotarget.27487. eCollection 2020 Feb 18. PMID: 32133046

We have confirmed the critical role of DNA-PK in HIV transcription and latency reactivation. Recently, we found that DNA-PK inhibitors are strong repressors of HIV transcription, replication and latency reactivation in patients’ PBMCs. Our results imply that DNA-PK inhibitors can supplement HAART regimens.

Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Shilpa Sonti, Sonia Zicari, Lin Sun, Aseel Alqatawni, Michael Bukrinsky, Gary Simon, Ashok Chauhan, Rene Daniel, and Mudit Tyagi; CBF-1 Promotes the Establishment and Maintenance of HIV Latency by Recruiting Polycomb Repressive Complexes, PRC1 and PRC2, at HIV LTR. Viruses. 2020 Sep; 12(9): 1040. doi: 10.3390/v12091040, PMID: 32961937, PMCID: PMC7551090.

We found the crucial role of CBF-1 in promoting both the establishment and maintenance HIV latency by recruiting Polycomb (PRC) corepressor complexes at HIV LTR. By developing a primary T cell-based model system for HIV latency, we confirmed for the first time that there are some critical differences in signaling pathways between transformed T cell lines and primary T cells, which regulates HIV latency.

Sahu G, Farley K, El-Hage N, Aiamkitsumrit B, Fassnacht R, Ochem A, Simon GL, Karn J, Hauser KF,  Tyagi M, Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR, Virology, 2016 Sep, 1doi:10.1016/j.virol.2015.03.036. PMCID: PMC4516702.

We found that cocaine promotes HIV replication by enhancing both the initiation and elongation phases of HIV transcription via activating selected signaling pathways and enzymes. For the first time by performing comprehensive analysis we determined the underlying molecular mechanisms that cocaine utilizes to promote both the initiation and elongation phases of HIV transcription, a necessity to generate complete genomic transcripts of HIV.

Marzio G*, Tyagi M*, Gutierrez MI, Giacca M. HIV-1 Tat transactivator recruits p300 and CREB-binding protein histone acetyltransferases to the viral promoter. Proc Natl Acad Sci U S A 1998 Nov 10;95 (23):13519-24 PMCID: PMC24851. *First Co-Authors 

My studies first time demonstrated how HIV transcription is facilitated by Tat induced transcriptionally active chromatin structures at HIV LTR. The produced article from that study has been cited more than 500 times.

Marzio G Tyagi M, Gutierrez MI, Giacca M. HIV-1 Tat transactivator recruits p300 and CREB-binding protein histone acetyltransferases to the viral promoter. Proc Natl Acad Sci U S A 1998 Nov 10;95 (23):13519-24.

My studies first time demonstrated how HIV transcription is facilitated by Tat induced transcriptionally active chromatin structures at HIV LTR. The produced article from that study has been cited more than 500 times.

Mudit Tyagi and Jonathan Karn; CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency. EMBO J. 2007 Dec 12;26(24):4985-95. Epub 2007 Nov 15. PMCID: PMC2140115

I found that CBF-1 facilitates HIV latency establishment by repressing HIV transcription. CBF-1 represses HIV transcription by recruiting histone deacetylases (HDACs) containing corepressor complexes at HIV LTR. We also developed a primary cell based model system for HIV latency. The unique advantage of our model is that it allows us to generate large amount of pure population of latently infected CD4+ T cells. This novelty of our system is the bases of the proposed project. Using this system, we confirmed for the first time that there are some critical differences in signaling pathways between transformed T cell lines and primary T cells.

Sahu G, Farley K, El-Hage N, Aiamkitsumrit B, Fassnacht R, Ochem A, Simon GL, Karn J, Hauser KF,  Tyagi M. Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR, Virology, 2016 Sep, 1doi:10.1016/j.virol.2015.03.036. 

We found that cocaine promotes HIV replication by enhancing both the initiation and elongation phases of HIV transcription via activating selected signaling pathways and enzymes. For the first time by performing comprehensive analysis we determined the underlying molecular mechanisms that cocaine utilizes to promote both the initiation and elongation phases of HIV transcription, a necessity to generate complete genomic transcripts of HIV.

Zicari S, Sharma AL, Sahu G, Dubrovsky L, Sun L, Yue H, Jada T, Ochem A, Simon G, Bukrinsky M, Tyagi M; DNA dependent protein kinase (DNA-PK) enhances HIV transcription by promoting RNA polymerase II activity and recruitment of transcription machinery at HIV LTR.; Oncotarget. 2020 Feb 18;11(7):699-726. doi: 10.18632/oncotarget.27487. eCollection 2020 Feb 18. PMID: 32133046.

We have confirmed the critical role of DNA-PK in HIV transcription and latency reactivation. Recently, we found that DNA-PK inhibitors are strong repressors of HIV transcription, replication and latency reactivation in patients’ PBMCs. Our results imply that DNA-PK inhibitors can supplement HAART regimens.