Dr. Dominic Paquin-Proulx obtained his Ph.D. in Biochemistry from Laval University, in Quebec City, Canada. His work focused on the effect of autoantibodies within intravenous immunoglobulins (IvIg) on B cells. Following completion of his PhD in 2010, Dr. Paquin-Proulx perform postdoctoral studies at Karolinska Institutet, in Stockholm Sweden, working on innate T cells (iNKT and MAIT cells) in the context of infections and immunodeficiencies. In 2015, He moved to the U.S., working as a Research Scientist at George Washington University in the lab of Dr Douglas Nixon to continue his work on innate T cells in viral infections. In 2017, he joined the innate immunology section of MHRP. He is the lead Scientist for the work on antibody effector functions as part of the system serology core.
Our laboratory focuses on the role of innate cells in HIV-infection and their contribution to viral control. Invariant Natural Killer T (iNKT) and Mucosal Associated Invariant T (MAIT) cells are innate T cells that recognize structures conserved across pathogens and are restricted by CD1d and MR1 respectively. These cells represent an important first line of defense against pathogens and have the capacity to modulate the adaptive immune response. We aim to understand how HIV impact these cells with the goal of restoring normal levels and functionality of these cells. Another area of interest is to understand how these cells respond to viral vectors and adjuvants used in HIV vaccine with the goal of leveraging their modulatory functions to boost the immune response. Natural killer (NK) cells are considered vital to early protection from diseases and support development of adaptive immune responses. NK cells support immune response through a variety of mechanisms: natural cytotoxicity, antibody dependent cellular cytotoxicity, cytokine/chemokine production and immune modulation through direct cell-to-cell interactions, however, less is known regarding NK cells response to vaccine. We aim to understand how adaptive NK cells may arise following different vaccine regimen and their potential role in preventing infection.
The Fc domain of antibodies can modulate cellular effector functions through interactions with Fc receptors (FcR) on innate immune cells. These interactions can result in activation of Ab-dependent cellular cytotoxicity (ADCC), phagocytosis (ADCP), complement deposition (ADCD), and pro-inflammatory cytokine production. Following the results of RV144, there is a growing understanding that these antibody effector functions are contributing to prevention of HIV infection. Our laboratory has developed high throughput assays to measure these functions from clinical trial samples. We are also investigating how adjuvant and innate immune cell sensing can be leveraged to further enhance these functions.
Om K*, Paquin-Proulx D*, Montero M*, Peachman K*, Shen S, Wieczorek L, Beck Z, Weiner JA, Kim D, Li Y, Mdluli T, Shubin Z, Bryant C, Sharma V, Tokarev A, Dawson P, White Y, Appelbe O, Klatt NR, Tovanabutra S, Estes J, Matyas G, Ferrari G, Alving C, Tomaras GD, Ackerman ME, Michael NL, Robb ML, Polonis V, Rolland M, Eller MA, Rao M, and Bolton DL. Adjuvanted HIV-1 vaccine protects against heterologous SHIV challenge and promotes antibody-dependent phagocytic responses. PLoS Pathogens. 2020. Sep 3;16(9):e1008764.
Colby DJ, Sarnecki M, Barouch H, Tipsuk S, Stieh DJ, Kroon E, Schuetz A, Intasan J, Sacdalan C, Pinyakorn S, Grandin P, Song H, Tovanabutra S, Shubin Z, Kim D, Paquin-Proulx D, Eller MA, Thomas R, de Souza M, Wieczorek L, Polonis VR, Pagliuzza A, Chomont N, Peter L, Nkolola JP, Vingerhoets J, Truyers C, Pau MG, Schuitemaker H, Phanuphak N, Michael NL, Robb ML, Tomaka F, and Ananworanich J. Ad26, MVA vaccines in acutely treated HIV: safety, immunogenicity and effect on viral rebound after ART interruption. Nature Medicine. 2020. Apr;26(4):498-501.
Lal KG, Kim D, Costanzo MC, Creegan M, Leeanshyah E, Dias J, Paquin-Proulx D, Eller LA, Schuetz A, Krebs SJ, Slike BM, Kibuuka H, Mangaga L, Nitayaphan S, Kosgei J, Bolton DL, Michael NL, Shacklett BL, Robb ML, Eller MA, and Sandberg JK. Dynamic MAIT cell response during acute HIV-1 infection with progressively enhanced innate-like features. Nature Communications. 2020. Jan 14;11(1):272
Crowell TA, Colby DJ, Pinyakorn S, Sacdalan C, Pagliuzza A, Intasan J, Benjapornpong K, Tangnaree K, Chomchey N, Kroon E, de Souza MS, Tovanabutra S, Rolland M, Eller MA, Paquin-Proulx D, Bolton DL, Tokarev A, Thomas R, Trautmann L, Krebs SJ, Modjarrad K, McDermott AB, Bailer RT, Doria-Rose N, Patel B, Gorelick RJ, Fullmer BA, Schuetz A, Grandin PV, O’Connell R, Ledgerwood JE, Graham BS, Tressler R, Mascola J, Chomont N, Michael NL, Robb ML, Phanuphak N, Ananworanich J, for the RV397 Study Group. Randomized trial of VRC01 in acutely-treated HIV-infected participants. Lancet HIV. 2019. May;6(5):e297-306
Alrubayyi A, Schuetz A, Lal, KG, Jongrakthaitae S, Paolino KM, Ake JA, Robb ML, de Souza MS, Michael NL, Paquin-Proulx D*, Eller MA*. A flow cytometry based assay that simultaneously measures cytotoxicity and monocyte mediated antibody dependent effector activity. Journal of Immunological Methods. 2018. Nov;462:74-82.
Paquin-Proulx D, Avelino-Silva V, Santos BAN, Silveira Barsotti N, Siroma F, Fernandes Ramos J, Coracini Tonacio A, Song A, Maestri A, Barros Cerqueira N, Felix AC, Levi ED, Greenspun BC, de Mulder Rougvie M, Rosenberg MG, Nixon DF, and Kallas EG. MAIT cells are activated in acute dengue infection and after in vitro zika infection. PLoS Neglected Tropical Diseases. 2018 Jan 22;12(1):e0006154.
Paquin-Proulx D, Greenspun BC, Costa EAS, Segrurado AC, Kallas EG, Nixon DF, Leal FE. MAIT cells are reduced in frequency and functionally impaired in human T lymphotropic virus type 1: potential clinical implications. PLoS One. 2017 Apr 6; 12(4):e0175345.
Paquin-Proulx D, Ching C, Vujkovic-Cvijin I, Fadrosh D, Loh L, Huang Y, Somsouk M, Lynch SV, Hunt PW, Nixon DF, and SenGupta D. Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection. Mucosal Immunology 2017 Jan;10(1):69-78.
Paquin-Proulx D, Gibbs A, Bächle S, Introini A, Checa A, Leeanshyah E, Wheelock CE, Nixon DF, Broliden K, Tjernlund A, Moll M, and Sandberg JK. Innate iNKT cell sensing of HIV-1 infection in dendritic cells is an early immune detection system inhibited by Nef and Vpu. Journal of Immunology 2016 Sep 1;197(5):1843-51.
Näslund TI, Paquin-Proulx D, Torregrosa Paredes P, Vallhov H, Sandberg JK and Gabrielsson S. Exosomes from breast milk inhibit HIV-1 infection of dendritic cells and subsequent viral transfer to CD4+ T cells. AIDS, 2014 Jan; 28:171-180.