Research
B cell activation results in a carefully tuned balance of short-term effector plasma cells and germinal center reactions yielding long-lived, affinity matured, memory B cells and plasma cells. Our lab studies how both cellular immunometabolism and organismal metabolism affect the outcome of B cell activation during an immune response. In doing this we strive to further understand how altered B cell metabolism leads to pathogenic antibody responses and ineffective humoral immunity. Our hope is that these studies will lead to improvements in therapies and vaccines and help us meet the challenges metabolic disorders pose to human health.
Biography
Brian Gaudette, PhD, is Assistant Staff in the Department of Inflammation and Immunity at Cleveland Clinic's Lerner Research Institute. Dr. Gaudette’s research focuses on the biochemical and metabolic pathways engaged during B cell activation and plasma cell differentiation. Prior to joining the Lerner Research Institute, Dr. Gaudette did his postdoctoral training at the University of Pennsylvania with Dr. David Allman during which time he uncovered a role for mTORC1 signaling in tuning ER stress in plasma cell differentiation. Dr. Gaudette received his PhD from Emory University where his dissertation in the lab of Dr. Lawrence Boise examined key changes in Bcl-2 family protein expression that protects differentiating plasma cells from apoptosis.
Education & Professional Highlights
Assistant Professor of Molecular Medicine, Cleveland Clinic Lerner College of Medicine (CCLCM) of Case Western Reserve University
Assistant Staff: Inflammation and Immunity, Lerner Research Institute, Appointed 2023
Research Associate: University of Pennsylvania 2020-2023
Postdoctoral Fellowship: University of Pennsylvania 2015-2020
Graduate Education: PhD: Emory University, Atlanta, GA. Immunology & Molecular Pathogenesis, 2014. Dissertation: Bcl-2 Family Protein Regulation in Differentiating and Malignant Plasma Cells
Undergraduate Education, BS, Clemson University, Clemson, SC Microbiology
"CIMER Trained Mentor" indicates the principal investigator has completed mentorship training based on curriculum from the Center for the Improvement of Mentored Experiences in Research, aimed at advancing mentoring relationships and promoting cultural change in research.
Research
B cell activation results in a carefully tuned balance of short-term effector plasma cells and germinal center reactions yielding long-lived, affinity matured, memory B cells and plasma cells. Our lab studies how both cellular immunometabolism and organismal metabolism affect the outcome of B cell activation during an immune response. In doing this we strive to further understand how altered B cell metabolism leads to pathogenic antibody responses and ineffective humoral immunity. Our hope is that these studies will lead to improvements in therapies and vaccines and help us meet the challenges metabolic disorders.
Our Team
Selected Publications
Selected Peer Reviewed Research Articles:
- Gómez Atria*, D, Gaudette, BT*, Londregan, J*, Kelly, S, Perkey, E, Allman, A, Srivastava, B, Koch, U, Radtke, F, Ludewig, B, Siebel, CW, Ryan, RJH, Robertson, TF, Burkhardt, JK, Pear, WS, Allman, D, Maillard, I, Stromal Notch ligands foster lymphopenia-driven functional plasticity and homeostatic proliferation of naïve B cells. J Clin Invest. 2022 Jul 1;132(13):e158885. doi: 10.1172/JCI158885. PMID: 35579963 *co-first authors
- Wilmore JR*, Gaudette BT*, Gómez Atria D, Rosenthal RL, Reiser SK, Meng W, Rosenfeld AM, Luning Prak ET, Allman D. IgA Plasma Cells Are Long-Lived Residents of Gut and Bone Marrow That Express Isotype- and Tissue-Specific Gene Expression Patterns. Front Immunol. 2021 Dec 24;12:791095. doi:10.3389/fimmu.2021.791095. eCollection 2021 PMID: 35003110 *co-first authors
- Gaudette BT, Roman CJ, Ochoa TA, Gómez Atria D, Jones DD, Siebel CW, Maillard I, Allman D. Resting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation. J Clin Invest. 2021 Oct 15;131(20):e151975. doi: 10.1172/JCI151975. PMID: 34473651
- Gaudette BT, Jones DD, Bortnick A, Argon Y, Allman D. mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion. Nat Commun. 2020 Feb 5;11(1):723. doi: 10.1038/s41467-019-14032-1. PMID: 32024827
- Wilmore JR, Gaudette BT, Gómez Atria D, Hashemi T, Jones DD, Gardner CA, Cole SD, Misic AM, Beiting DP, Allman D. Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis. Cell Host Microbe. 2018 Mar 14;23(3):302-311.e3. doi:10.1016/j.chom.2018.01.005. Epub 2018 Feb 22. PMID: 29478774
- Jones DD, Gaudette BT, Wilmore JR, Chernova I, Bortnick A, Weiss BM, Allman D. mTOR has distinct functions in generating versus sustaining humoral immunity. J Clin Invest. 2016 Nov 1;126(11):4250-4261. doi: 10.1172/JCI86504. Epub 2016 Oct 17. PMID: 27760048
- Gaudette BT, Dwivedi B, Chitta KS, Poulain S, Powell D, Vertino P, Leleu X, Lonial S, Chanan-Khan AA, Kowalski J, Boise LH. Low expression of pro-apoptotic Bcl-2 family proteins sets the apoptotic threshold in Waldenström macroglobulinemia. Oncogene. 2016 Jan 28;35(4):479-90. doi: 10.1038/onc.2015.103. Epub 2015 Apr 20. PMID: 25893290
- Gaudette BT, Iwakoshi NN, Boise LH. Bcl-xL protein protects from C/EBP homologous protein (CHOP)-dependent apoptosis during plasma cell differentiation. J Biol Chem. 2014 Aug 22;289(34):23629-40. doi: 10.1074/jbc.M114.569376. Epub 2014 Jul 14. PubMed PMID: 25023286; PubMed Central PMCID: PMC4156059.
Review Articles
- Gaudette BT, Allman D. Biochemical coordination of plasma cell genesis. Immunol Rev. 2021 Sep;303(1):52-61. doi: 10.1111/imr.12992. Epub 2021 Jul 26. PMID: 34313339
- Allman D, Wilmore JR, Gaudette BT. The continuing story of T-cell independent antibodies. Immunol Rev. 2019 Mar;288(1):128-135. doi: 10.1111/imr.12754. Review. PMID: 30874357