Alberto Bosque, Ph.D., M.B.A., joined the George Washington University in November 2016 as Assistant Professor in the Department of Microbiology, Immunology and Tropical Medicine. He is a biochemist with considerable experience in cell biology and signal transduction. Dr. Bosque received his Bachelor’s degree in Biochemistry with high honors from the University of Zaragoza, Spain in 2001. During his graduate studies at the University of Zaragoza in the laboratory of Dr. Alberto Anel, he studied the mechanisms of downregulation of human T cell immune responses and their implication to Autoimmune Lymphoproliferative Syndromes (ALPS). After obtaining a Ph.D. in Biochemistry and Molecular and Cellular Biology with honors “cum laude”, Dr. Bosque moved to the US and joined the laboratory of Dr. Vicente Planelles at the University of Utah, first with a postdoctoral fellowship from the Spanish Government followed by a Mathilde Krim Postdoctoral Fellowship from The Foundation for AIDS Research (amfAR). During his postdoctoral studies, he developed one of the first primary cell models of HIV-1 latency (Bosque and Planelles, Blood, 2009). In 2011, Dr. Bosque became a Research Assistant Professor at the University of Utah and in 2015 an Assistant Professor. During his time as Faculty at the University of Utah, he also completed with honors a Master Degree in Business Administration (M.B.A.). Dr. Bosque is an Associate Professor in the Department of Microbiology, Immunology & Tropical Medicine at GW. Dr. Bosque has been involved in HIV cure research for the last 15 years focusing on the discovery and characterization of signaling pathways that can both reactivate latent HIV-1 in resting CD4+ T cells and enhance immune effector functions of NK and CD8+ T cells. He has a long-standing funding record as Principal Investigator in HIV cure research, including a Grand Challenges Exploration from the Bill and Melinda Gates Foundation as well as an R21, R21/R33, R56 and two R01s from NIAID, and several other grants as collaborator.
Honors and Awards
2009 Mathilde Krim Postdoctoral Research Fellowship, The Foundation for AIDS Research (amfAR), USA. 2007 Postdoctoral Research Fellowship, Ministry of Science and Technology, Spain. 2006 Award for the most outstanding graduate student in Health Sciences, University of Zaragoza, Spain. 2002 Graduate Research Fellowship, Ministry of Science and Technology, Spain. 2001 Award for the most outstanding graduate student in Biochemistry, University of Zaragoza, Spain. 2000 Undergraduate Research Fellowship, University of Zaragoza, Spain.
Previous Contributions to Science
A. During my doctoral training, I worked on characterizing the role of pro- and anti-apoptotic proteins in the down-modulation of the T cell immune response. My work focused on understanding how these proteins are regulated in human T cells and how its regulation is important for autoimmune lymphoproliferative syndromes (ALPS). In particular, I characterized a novel signaling pathway that connects the two main signaling routs that control T-cell activation: death receptor-mediated activation-induced cell death and apoptosis by cytokine deprivation.
1. Bosque A , Pardo J, Martinez-Lorenzo MJ, Iturralde M, Marzo I, Pineiro A, Alava MA, Naval J, Anel A (2005). Down-regulation of normal human T cell blast activation: roles of APO2L/TRAIL, FasL, and c- FLIP, Bim, or Bcl-x isoform expression. J Leukoc Biol, 77(4), 568-78.
2. Del-Rey M, Ruiz-Contreras J, Bosque A , Calleja S, Gomez-Rial J, Roldan E, Morales P, Serrano A, Anel A, Paz-Artal E, Allende LM (2006). A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome. Blood, 108(4), 1306-12.
3. Bosque A , Marzo I, Naval J, Anel A (2007). Apoptosis by IL-2 deprivation in human CD8+ T cell blasts predominates over death receptor ligation, requires Bim expression and is associated with Mcl-1 loss. Mol Immunol, 44(6), 1446-53.
4. Bosque A , Aguilo JI, Alava MA, Paz-Artal E, Naval J, Allende LM, Anel A (2007). The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling. Blood, 109(4), 1627-35.
B. My doctoral training gave me expertise working with human primary lymphocytes. I used this expertise to generate one of the first primary cell models of HIV-1 latency. This model has become a suitable model to study the mechanism that are involved in the establishment and reactivation of latent HIV-1. Using this model, I characterized the signaling pathway that leads to viral reactivation after antigen stimulation. Furthermore, I characterized the role of homeostatic proliferation as a means to perpetuate and possibly expand the latent reservoir. Recently, we have uncovered a novel mechanism controlling HIV-1 latency. Using RNA-seq, we discovered that HIV-1 infection leads to the transcriptional activation of p53. Inhibition of the transcriptional activation of p53 using pifithrin-, a specific chemical inhibitor, leads to the silencing of the latent reservoir. Finally, this model allows to study the role of other biological variables such as sex and age influence the establishment and reactivation of the latent reservoir.
1. Bosque A Planelles V (2009). Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells. Blood, 113(1), 58-65. PMCID: PMC2614643.
2. Bosque A , Famiglietti M, Weyrich AS, Goulston C, Planelles V (2011). Homeostatic proliferation fails to efficiently reactivate HIV-1 latently infected central memory CD4+ T cells. PLoS Pathog, 7(10), e1002288. PMCID: PMC3188522.
3 White CH, Moesker B, Beliakova-Bethell N, Martins LJ, Spina CA, Margolis DM, Richman DD, Planelles V, Bosque A*, Woelk CH* (2016). Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model. PLoS Pathog. 12(11): e1006026. *Corresponding author.
4. Macedo AB, Resop RS, Martins LJ, Szaniawski MA, Sorensen ES, Spivak AM, Nixon DF, Jones RB, Planelles V, Bosque A. (2018). Influence of biological sex, age and HIV status in an in vitro primary cell model of HIV latency using a CXCR4 tropic virus. AIDS Res Hum Retroviruses, Sep; 34(9):769-777. PMCID: PMC6152854
C. My research has also been actively involved in discovering and characterizing LRAs. In particular, my lab is investigating two different “shock and kill” strategies towards HIV eradication. One is the use of Pathogen Recognition Receptor agonists and the other one is to modulate STAT5 activity using a novel family of compounds that we have recently characterized.
1. Novis CL, Archin NM, Buzon MJ, Verdin E, Round JL, Lichterfeld M, Margolis DM, Planelles V, Bosque A (2013). Reactivation of latent HIV-1 in central memory CD4+ T cells through TLR-1/2 stimulation. Retrovirology, 10(1), 119. PMCID: PMC3826617.
2. Bosque A*, Nilson KA, Macedo AB, Spivak AM, Archin NM, Van Wagoner RM, Martins LJ, Novis CL, Szaniawski MA, Ireland CM, Margolis DM, Price DH, Planelles V* (2017). Benzotriazoles reactivate latent HIV-1 through inactivation of STAT5 SUMOylation. Cell Reports. 18 (5),1324–1334. *Corresponding Author. PMCID: PMC5461578
3. Macedo AB, Novis CL, De Asis CM, Sorensen ES, Moszczynski P, Huang SH, Ren Y, Spivak AM, Jones RB, Planelles V, Bosque A (2018). Dual TLR2 and TLR7 agonists as HIV latency reversing agents. The Journal of Clinical Investigation Insight. Oct 4;3(19). PMCID: PMC6237480
4. Sorensen ES*, Macedo AB*, Resop RS, Howard JN, Nell R, Sarabia I, Newman D, Ren Y, Jones RB, Planelles V, Spivak AM,Bosque A (2020). “Structure activity relationship analysis of benzotriazine analogues as HIV-1 Latency Reversing Agents”. Antimicrobial Agents and Chemotherapy. Jul 22;64(8):e00888-20. PMID: 32482680. *Co-first author
D. Furthermore, my lab has been actively collaborating with researchers at GW and in other institutions to further characterize other mechanisms involved in HIV latency and persistence.
1. Huang SH, Ren Y, Thomas AS, Chan D, Mueller S, Ward AR, Patel S, Bollard CM, Russel Cruz C, Karandish S, Truong R, Macedo AB, Bosque A, Kovacs C, Benko E, Piechocka-Trocha A, Wong H, Jeng E, Nixon DF, Ho YC, Siliciano RF, Walker BD, Jones RB (2018). Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells. The Journal of Clinical Investigation. Feb 1; 128(20):876-889. PMCID: PMC5785246.
2. Ren Y, Huang SH, Patel S, Conce Alberto WD, Magat D, Ahimovic D, Macedo AB, Durga R, Chan D, Zale E, Mota TM, Truong R, Rohwetter T, McCann CD, Kovacs CM, Benko E, Wimpelberg A, Cannon C, Hardy WD, Bosque A, Bollard CM, Jones RB (2020). BCL-2 Antagonism Sensitizes Cytotoxic T Cell-Resistant HIV Reservoirs to Elimination Ex Vivo. The Journal of Clinical Investigation. May 1;130(5):2542-2559. PMCID: PMC7191002.
3. Sweeney EE, Balakrishnan PB, Powell AB, Bowen A, Sarabia I, Burga RA, Jones RB,Bosque A, Cruz CRY, Fernandes R (2020). PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function. Nano Research. 13: 736–744.
4. Moron-Lopez S, Telwatte S, Sarabia I, Battivelli E, Montano M, Macedo A, Aran D, Butte AJ, Jones RB, Bosque A, Verdin E, Greene WG, Wong JK, Yukl SA (2020). “Human splice factors contribute to latent HIV infection in primary cell models and blood CD4+ T cells from ART-treated individuals”. PLoS Pathogens. Nov 30;16(11):e1009060.