Satish Pillai, PhD

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Satish Pillai, PhD

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Senior Investigator, Viral Pathogenesis, Vitalant Research Institute
Professor, School of Medicine
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Biography

My laboratory uses a systems biology approach to decipher the antiretroviral effects of IFN-α in vivo, by studying host gene expression, viral production and viral evolution in HIV-1-infected individuals undergoing IFN-α therapy. Recent data generated by our group strongly suggest that IFN-α suppresses HIV-1 replication in chronically-infected individuals by inducing intrinsic cellular inhibitors of retroviral replication known as host restriction factors. One of these factors, the cytidine deaminase APOBEC3G, blocks HIV-1 infection by hyper-mutating the viral genome such that it no longer encodes functional proteins that are necessary for viral replication. Another factor, the type 2 integral membrane protein BST-2/tetherin, blocks HIV-1 infection by restricting the release of fully formed progeny virions from infected cells. Our data warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

In addition to my principal research projects involving IFN-α and cell-intrinsic immunity, I participate as a bioinformaticist and phylogeneticist in a number of HIV/AIDS collaborations with researchers at the San Francisco VA Medical Center (SFVAMC), San Francisco General Hospital (SFGH) and the Gladstone Institute of Virology and Immunology (GIVI).

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  1. Siegel DA, Thanh C, Wan E, Hoh R, Hobbs K, Pan T, Gibson EA, Kroetz DL, Martin J, Hecht F, Pilcher C, Martin M, Carrington M, Pillai S, Busch MP, Stone M, Levy CN, Huang ML, Roychoudhury P, Hladik F, Jerome KR, Kiem HP, Henrich TJ, Deeks SG, Lee SA. Host variation in type I interferon signaling genes (MX1), C-C chemokine receptor type 5 gene, and major histocompatibility complex class I alleles in treated HIV+ noncontrollers predict viral reservoir size. AIDS. 2023 Mar 01; 37(3):477-488.
  2. Yeung ST, Premeaux TA, Du L, Niki T, Pillai SK, Khanna KM, Ndhlovu LC. Galectin-9 protects humanized-ACE2 immunocompetent mice from SARS-CoV-2 infection. Front Immunol. 2022; 13:1011185.
  3. Müller-Schiffmann A, Michon M, Lingappa AF, Yu SF, Du L, Deiter F, Broce S, Mallesh S, Crabtree J, Lingappa UF, Macieik A, Müller L, Ostermann PN, Andrée M, Adams O, Schaal H, Hogan RJ, Tripp RA, Appaiah U, Anand SK, Campi TW, Ford MJ, Reed JC, Lin J, Akintunde O, Copeland K, Nichols C, Petrouski E, Moreira AR, Jiang IT, DeYarman N, Brown I, Lau S, Segal I, Goldsmith D, Hong S, Asundi V, Briggs EM, Phyo NS, Froehlich M, Onisko B, Matlack K, Dey D, Lingappa JR, Prasad MD, Kitaygorodskyy A, Solas D, Boushey H, Greenland J, Pillai S, Lo MK, Montgomery JM, Spiropoulou CF, Korth C, Selvarajah S, Paulvannan K, Lingappa VR. A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex. bioRxiv. 2022 Jul 19.
  4. Khanna K, Raymond WW, Jin J, Charbit AR, Gitlin I, Tang M, Werts AD, Barrett EG, Cox JM, Birch SM, Martinelli R, Sperber HS, Franz S, Duff T, Hoffmann M, Healy AM, Oscarson S, Pöhlmann S, Pillai SK, Simmons G, Fahy JV. Exploring antiviral and anti-inflammatory effects of thiol drugs in COVID-19. Am J Physiol Lung Cell Mol Physiol. 2022 09 01; 323(3):L372-L389.
  5. Du L, Bouzidi MS, Gala A, Deiter F, Billaud JN, Yeung ST, Dabral P, Jin J, Simmons G, Dossani Z, Niki T, Ndhlovu LC, Greenland JR, Pillai SK. Human Galectin-9 Potently Enhances SARS-CoV-2 Replication and Inflammation in Airway Epithelial Cells. bioRxiv. 2022 May 16.
  6. Bhattacharyya A, Boostanpour K, Bouzidi M, Magee L, Chen TY, Wolters R, Torre P, Pillai SK, Bhattacharya M. IL10 trains macrophage profibrotic function after lung injury. Am J Physiol Lung Cell Mol Physiol. 2022 03 01; 322(3):L495-L502.
  7. Khanna K, Raymond W, Charbit AR, Jin J, Gitlin I, Tang M, Sperber HS, Franz S, Pillai S, Simmons G, Fahy JV. Binding of SARS-CoV-2 spike protein to ACE2 is disabled by thiol-based drugs; evidence from in vitro SARS-CoV-2 infection studies. bioRxiv. 2020 Dec 08.
  8. Hiatt J, Cavero DA, McGregor MJ, Zheng W, Budzik JM, Roth TL, Haas KM, Wu D, Rathore U, Meyer-Franke A, Bouzidi MS, Shifrut E, Lee Y, Kumar VE, Dang EV, Gordon DE, Wojcechowskyj JA, Hultquist JF, Fontaine KA, Pillai SK, Cox JS, Ernst JD, Krogan NJ, Marson A. Efficient generation of isogenic primary human myeloid cells using CRISPR-Cas9 ribonucleoproteins. Cell Rep. 2021 May 11; 35(6):109105.
  9. Egedal JH, Xie G, Packard TA, Laustsen A, Neidleman J, Georgiou K, Pillai SK, Greene WC, Jakobsen MR, Roan NR. Hyaluronic acid is a negative regulator of mucosal fibroblast-mediated enhancement of HIV infection. Mucosal Immunol. 2021 09; 14(5):1203-1213.
  10. Rutishauser RL, Deguit CDT, Hiatt J, Blaeschke F, Roth TL, Wang L, Raymond KA, Starke CE, Mudd JC, Chen W, Smullin C, Matus-Nicodemos R, Hoh R, Krone M, Hecht FM, Pilcher CD, Martin JN, Koup RA, Douek DC, Brenchley JM, Sékaly RP, Pillai SK, Marson A, Deeks SG, McCune JM, Hunt PW. TCF-1 regulates HIV-specific CD8+ T cell expansion capacity. JCI Insight. 2021 02 08; 6(3).
  11. Gramatica A, Schwarzer R, Brantley W, Varco-Merth B, Sperber HS, Hull PA, Montano M, Migueles SA, Rosenthal D, Hogan LE, Johnson JR, Packard TA, Grimmett ZW, Herzig E, Besnard E, Nekorchuk M, Hsiao F, Deeks SG, Snape M, Kiernan B, Roan NR, Lifson JD, Estes JD, Picker LJ, Verdin E, Krogan NJ, Henrich TJ, Connors M, Ott M, Pillai SK, Okoye AA, Greene WC. Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity Ex Vivo and In Vivo. J Virol. 2021 Feb 03.
  12. Ng DL, Goldgof GM, Shy BR, Levine AG, Balcerek J, Bapat SP, Prostko J, Rodgers M, Coller K, Pearce S, Franz S, Du L, Stone M, Pillai SK, Sotomayor-Gonzalez A, Servellita V, Martin CSS, Granados A, Glasner DR, Han LM, Truong K, Akagi N, Nguyen DN, Neumann NM, Qazi D, Hsu E, Gu W, Santos YA, Custer B, Green V, Williamson P, Hills NK, Lu CM, Whitman JD, Stramer SL, Wang C, Reyes K, Hakim JMC, Sujishi K, Alazzeh F, Pham L, Thornborrow E, Oon CY, Miller S, Kurtz T, Simmons G, Hackett J, Busch MP, Chiu CY. SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood. Nat Commun. 2020 09 17; 11(1):4698.
  13. Sperber HS, Togarrati PP, Raymond KA, Bouzidi MS, Gilfanova R, Gutierrez AG, Muench MO, Pillai SK. μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies. FASEB J. 2020 11; 34(11):14615-14630.
  14. Marques de Menezes EG, Jang K, George AF, Nyegaard M, Neidleman J, Inglis HC, Danesh A, Deng X, Afshari A, Kim YH, Billaud JN, Marson K, Pilcher CD, Pillai SK, Norris PJ, Roan NR. Seminal Plasma-Derived Extracellular-Vesicle Fractions from HIV-Infected Men Exhibit Unique MicroRNA Signatures and Induce a Proinflammatory Response in Cells Isolated from the Female Reproductive Tract. J Virol. 2020 07 30; 94(16).
  15. Vallejo-Gracia A, Chen IP, Perrone R, Besnard E, Boehm D, Battivelli E, Tezil T, Krey K, Raymond KA, Hull PA, Walter M, Habrylo I, Cruz A, Deeks S, Pillai S, Verdin E, Ott M. FOXO1 promotes HIV latency by suppressing ER stress in T cells. Nat Microbiol. 2020 09; 5(9):1144-1157.
  16. Ng DL, Goldgof GM, Shy BR, Levine AG, Balcerek J, Bapat SP, Prostko J, Rodgers M, Coller K, Pearce S, Franz S, Du L, Stone M, Pillai SK, Sotomayor-Gonzalez A, Servellita V, Martin CSS, Granados A, Glasner DR, Han LM, Truong K, Akagi N, Nguyen DN, Neumann NM, Qazi D, Hsu E, Gu W, Santos YA, Custer B, Green V, Williamson P, Hills NK, Lu CM, Whitman JD, Stramer S, Wang C, Reyes K, Hakim JMC, Sujishi K, Alazzeh F, Pham L, Oon CY, Miller S, Kurtz T, Hackett J, Simmons G, Busch MP, Chiu CY. SARS-CoV-2 seroprevalence and neutralizing activity in donor and patient blood from the San Francisco Bay Area. medRxiv. 2020 May 25.
  17. H. Sperber, T. Ma, N.R. Roan, S.K. Pillai. OP 1.1 Expression profiling of HIV latently-infected cells using nanostring and mass cytometry. Journal of virus eradication. 2019 Dec 1; 5:1.
  18. H. Sperber, P.P. Togarrati, K. Raymond, M.S. Bouzidi, R. Gilfanova, M.O. Muench, S.K. Pillai. PP 2.6 µ-Lat: a high-throughput humanised mouse model of latent HIV infection. Journal of virus eradication. 2019 Dec 1; 5:19.
  19. H. Sperber, T. Ma, N.R. Roan, S.K. Pillai. OP 1.1 Expression profiling of HIV latently-infected cells using nanostring and mass cytometry. Journal of virus eradication. 2019 Dec 1; 5:1.
  20. H. Sperber, P.P. Togarrati, K. Raymond, M.S. Bouzidi, R. Gilfanova, M.O. Muench, S.K. Pillai. PP 2.6 µ-Lat: a high-throughput humanised mouse model of latent HIV infection. Journal of virus eradication. 2019 Dec 1; 5:19.
  21. Li Z, Wu J, Chavez L, Hoh R, Deeks SG, Pillai SK, Zhou Q. Reiterative Enrichment and Authentication of CRISPRi Targets (REACT) identifies the proteasome as a key contributor to HIV-1 latency. PLoS Pathog. 2019 01; 15(1):e1007498.
  22. Premeaux TA, D'Antoni ML, Abdel-Mohsen M, Pillai SK, Kallianpur KJ, Nakamoto BK, Agsalda-Garcia M, Shiramizu B, Shikuma CM, Gisslén M, Price RW, Valcour V, Ndhlovu LC. Elevated cerebrospinal fluid Galectin-9 is associated with central nervous system immune activation and poor cognitive performance in older HIV-infected individuals. J Neurovirol. 2019 04; 25(2):150-161.
  23. Laustsen A, Bak RO, Krapp C, Kjær L, Egedahl JH, Petersen CC, Pillai S, Tang HQ, Uldbjerg N, Porteus M, Roan NR, Nyegaard M, Denton PW, Jakobsen MR. Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function. Nat Commun. 2018 08 30; 9(1):3525.
  24. Emilie Battivelli, Matthew S. Dahabieh, Mohamed Abdel-Mohsen, J. Peter Svensson, Israel Tojal Da Silva, Lilian B. Cohn, Andrea Gramatica, Steven Deeks, Warner Greene, Satish K. Pillai, Eric Verdin. D-106 Chromatin Functional States Correlate with the Reversal of Latently HIV-1 Infected Primary CD4+ T cells. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2018 Apr 1; 77(&NA;):40.
  25. Danesh A, Inglis HC, Abdel-Mohsen M, Deng X, Adelman A, Schechtman KB, Heitman JW, Vilardi R, Shah A, Keating SM, Cohen MJ, Jacobs ES, Pillai SK, Lacroix J, Spinella PC, Norris PJ. Granulocyte-Derived Extracellular Vesicles Activate Monocytes and Are Associated With Mortality in Intensive Care Unit Patients. Front Immunol. 2018; 9:956.