Biography
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 the completion of his Ph.D. 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. His current research is focused on understanding innate immune responses in the context of vaccination and natural infection.
Research
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.
Selected Publications
Dussupt V, Sankhala RS, Mendez-Rivera L, Townsley SM, Schmidt F, Wieczorek L, Lal KG, Donofrio GC, Tran U, Jackson ND, Zaky WI, Zemil M, Tritsch SR, Chen WH, Martinez EJ, Ahmed A, Choe M, Chang WC, Hajduczki A, Jian N, Peterson CE, Rees PA, Rutkowska M, Slike BM, Selverian CN, Swafford I, Teng IT, Thomas PV, Zhou T, Smith CJ, Currier JR, Kwong PD, Rolland M, Davidson E, Doranz BJ, Mores CN, Hatziioannou T, Reiley WW, Bieniasz PD, Paquin-Proulx D, Gromowski GD, Polonis VR, Michael NL, Modjarrad K, Joyce MG, Krebs SJ. Low-dose in vivo protection and neutralization across SARS-CoV-2 variants by monoclonal antibody combinations. Nature Immunology. 2021 Dec;22(12):1503-1514
Paquin-Proulx D, Lal KG, Phuang-Ngern Y, Creegan M, Tokarev A, Suhkumvittaya S, Alrubayyi A, Kroon E, Pinyakor S, Slike BM, Bolton DL, Krebs JS, Eller LA, Sajjaweerawan C, Pagliuzza A, Chomont N, Rerknimitr R, Chomchey N, Phanuphak N, de Souza MS, Michael NL, Robb ML, Ananworanich J, Sandberg JK, Eller MA*, and Schuetz A*. Preferential and persistent impact of acute HIV-1 infection on CD4+ iNKT cells in colonic mucosa. PNAS. 2021 Nov 16;118(46) :e210472118.
Paquin-Proulx D*, Gunn BM*, Alrubayyi A, Clark DV, Creegan M, Kim D, Kibuuka D, Millard M, Wakabi S, Eller LA, Michael NL, Schoepp RJ, Hepburn MJ, Hensley LE, Robb ML, Alter G,# and Eller MA #. Associations between antibody Fc-mediated effector functions and long-term sequelae in Ebola virus survivors. Frontiers in Immunology. 2021 May 20;12 :682120
Lal K, Phuang-Ngern Y, Suhkumvittaya S, Leeansyah E, Alrubayyi A, Dias J, Waickman A, Kim D, Kroon E, Pinyakorn S, Eller LA, Maciel Jr M, Rerknimitr R, Chomchey N, Phanuphak N, de Souza MS, Nitayaphan S, Ake JA, Vasan S, Robb ML, Ananworanich J, Sandberg JK, Schuetz A, Eller MA, and Paquin-Proulx D. Longitudinal analysis of peripheral and colonic CD161+ CD4+ T cell dysfunction in acute HIV-1 infection and effects of early treatment initiation. Viruses. 2020 Dec 11;12(12):1426.
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
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, 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.