Entering Class: 2010
Biomedical Engineering major
University of Minnesota
Microbiology, Immunology and Cancer Biology Graduate Program
Thesis Advisor: Thomas Griffith, Ph.D.
Sepsis strikes 750,000 Americans every year with an estimated 210,000 of these patients dying—far more than the number of U.S. deaths from prostate, breast cancer and AIDS combined. While some of these deaths do occur during the acute, inflammatory stages of sepsis, as many as two-thirds of these patients survive the initial infection and perish due to secondary, hospital-acquired infections. Although most of sepsis research has been focused in understanding the acute, inflammatory stage of sepsis, this high susceptibility to infections has led clinicians and researchers to the idea that the chronic stage of sepsis is just as relevant and is characterized by clinically important immunosuppression. Despite this, very little is known about the mechanisms behind immunosuppression in sepsis.
CD4 T cells, which are essential for the coordination of successful immune responses to opportunistic pathogens, are severely depleted during the acute stage of sepsis and gradually recovered throughout the immunosuppressive phase of sepsis. However, little is known regarding the mechanism(s) of recovery and extent to which sepsis impairs CD4 T cell recovery or function in surviving patients. Our preliminary studies indicate that antigen (Ag)-specific CD4 T cell responses to bacterial and viral pathogens are impaired over a prolonged period of time after septic injury. In addition, certain Ag-specific CD4 T cell populations do not recover completely, despite apparent numerical recovery of CD4 T cells. We suspect that the prolonged loss of Ag-specific CD4 T cells is suggestive of “holes” within the T cell repertoire of sepsis survivors. However, the impact of repertoire attrition in the context of an opportunistic infection after sepsis is not known. The objectives of my research project are to study a potential new mechanism of CD4 T cell impairment during the immunosuppressive stage of sepsis. The findings of this project will enhance our understanding of why septic patients succumb to opportunistic infections.
Cabrera-Perez J, Badovinac VP, Griffith TS. Enteric immunity, the gut microbiome, and sepsis: Rethinking the germ theory of disease. Exp Biol Med (Maywood). 2017 Jan;242(2):127-139. PMCID: PMC5167116
Cabrera-Perez J, Babcock JC, Dileepan T, Murphy KA, Kucaba TA, Badovinac VP, Griffith TS. Gut Microbial Membership Modulates CD4 T Cell Reconstitution and Function after Sepsis. J Immunol. 2016 Sep 1;197(5):1692-8. PMCID: PMC4992581
Cabrera-Perez J, Condotta SA, James BR, Kashem SW, Brincks EL, Rai D, Kucaba TA, Badovinac VP, Griffith TS. Alterations in antigen-specific naive CD4 T cell precursors after sepsis impairs their responsiveness to pathogen challenge. J Immunol. 2015 Feb 15;194(4):1609-20. PMCID: PMC4412277
Cabrera-Perez J, Condotta SA, Badovinac VP, Griffith TS. Impact of sepsis on CD4 T cell immunity. J Leukoc Biol. 2014 Nov;96(5):767-77. Review. PMCID: PMC4197564
Condotta SA, Cabrera-Perez J, Badovinac VP, Griffith TS. T-cell-mediated immunity and the role of TRAIL in sepsis-induced immunosuppression. Crit Rev Immunol. 2013;33(1):23-40. PMCID: PMC3625932
Publications prior to entering the Program:
Lu SX, Alpdogan O, Lin J, Balderas R, Campos-Gonzalez R, Wang X, Gao GJ, Suh D, King C, Chow M, Smith OM, Hubbard VM, Bautista JL, Cabrera-Perez J, Zakrzewski JL, Kochman AA, Chow A, Altan Bonnet G, van den Brink MR. STAT-3 and ERK 1/2 phosphorylation are critical for T cell alloactivation and graft-versus-host-disease. Blood. 200; 112: 5254-5258. PMCID: PMC2597618
Zakrzewski JL, Suh DY, Markley JC, Smith OM, King C, Goldberg GL, Jenq R, Holland AM, Grubin J, Cabrera-Perez J, Brentjens RJ, Lu SX, Rizzuto G, Sant’Angelo DB, Riviere I, Sadelain M, Heller G, Zúñiga-Pflücker JC, Lu C & van den Brink MRM. Tumor immunotherapy across MHC barriers using allogeneic T cell precursors. Nature Biotechnology. 2008; 26: 453–461. PMCID: PMC2731996
Zakrzewski JL, Kochman AA, Lu SX, Terwey TH, Kim TD, Hubbard VM, Muriglan SJ, Suh DY, Smith OM, Grubin J, Patel N, Chow A, Cabrera-Perez J, Radhakrishnan R, Diab A, Perales MA, Rizzuto G, Menet E, Pamer EG, Heller G, Zúñiga-Pflücker JC, Alpdogan O, & van den Brink MRM. Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation. Nature Medicine. 2006; 12: 1039-1047.