Elizabeth A. Wohlfert Ph.D.
Elizabeth A. Wohlfert
Ph.D.
Associate Professor
Department of Microbiology and Immunology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Immunology; Infectious Disease
Professional Summary:
The fundamental question that drives the research in my laboratory is how the immune response is regulated so that an invading pathogen is eliminated or controlled with minimal collateral damage to the host. A protective immune response is required in order to survive infection by a microorganism, such as parasites, bacteria or viruses. If the immune response is too weak then the pathogen will win, while an immune response that is too strong can cause collateral damage, called immune-mediated pathology and disease. My laboratory asks what is important for balancing a protective immune response and preventing immune-mediated pathology during chronic infection. My research focuses on an essential immune cell, the T regulatory cell (Tregs) that regulates the amount of immune response directed at invading microorganisms. In addition to preventing unwanted immune responses directed at the body’s own tissues, Tregs play an important role in tuning the immune response to infection. If there is an impairment of Treg development or function then uncontrolled inflammation, immune-mediated pathology, and disease can occur. We use the parasite Toxoplasma gondii to investigate how immune regulation is altered by chronic infection. Ingestion of T. gondii results in a chronic infection with tissue cysts residing in skeletal muscle and the central nervous system.
My laboratory uses a mouse model of Toxoplasma infection to study how the establishment of infection and its chronicity alter Treg and their responses. We showed that in mice, T. gondii infection causes severe inflammation of the muscle (myositis) and a loss of muscle function. We found that this happens because the infection alters the function of Tregs and they acquire a tissue injurious function, instead of a tissue reparative function. We further showed that chronic infection stunts the ability of macrophages to participate in the wound healing response. Finally, we found that chronic infection impairs the renewal of muscle stem cells that are required for the regeneration of skeletal muscle. We are currently asking questions about how the interactions between these 3 critical cell types occur, and how chronic infection impacts this cellular network. We are also interested in identifying methods to intervene and dampen inflammation and promote the return of function to the muscle.
Education and Training:
- PhD, Immunology, University of Connecticut Health Center (2007)
- BS, Pathobiology, University of Connecticut, Cum Laude (2002)
Employment:
- Associate Professor, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences (2022-present)
- Adjunct Member, Tumor Immunology and Immunotherapy Program, Roswell Park Cancer Institute (2014-present)
- Assistant Professor, Microbiology and Immunology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences (2018–2022)
- Research Assistant Professor, Microbiology and Immunology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences (2017–2018)
- Assistant Professor, Microbiology and Immunology, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences (2013–2017)
- Research Fellow, Laboratory of Parasitic Diseases, National Institutes of Health National Institute for Allergy and Infectious Diseases (2010–2013)
- Post Doctoral Fellow, Laboratory of Parasitic Diseases, National Institutes of Health National Institute for Allergy and Infectious Diseases (2007–2010)
Awards and Honors:
- Early Career Faculty Travel Award (2020)
- Early Career Faculty Travel Award (2018)
- Careers in Immunology Fellowship (2016)
- Early Career Faculty Travel Award (2016)
- Ray Owen Poster Award, 52nd Midwinter Conference of Immunologists (2013)
- Fellows Award for Research Excellence, NIH (2010)
- Research Fellow Award (2009)
- Fellows Award for Research Excellence, NIH (2008)
- Keystone Travel Award, Regulatory T cells Meeting (2007)
- Lepow Fellowship (2006)
- Huang Foundation Trainee Achievement Award (2006)
- Keystone Travel Award, Tolerance, Autoimmunity and Regulation Meeting (2006)
- Keystone Travel Award, Tolerance, Autoimmunity and Regulation Meeting (2004)
Research Expertise:
- Immune Regulation and Wound Repair: Examining the interactions between Tregs, macrophages and stromal cells in skeletal muscle
- Immunobiology: Stability and function of regulatory T cell
- Immunoparasitology: Immune regulation in tissues during parasitic infections
- Mucosal immunology: Regulatory T cell function in the gastrointestinal tract
Research Centers:
- Witebsky Center for Microbial Pathogenesis and Immunology
Grants and Sponsored Research:
- February 2022–March 2027
T Regulatory cell responses in Toxoplasma-infected muscle
NIAID/NIH
Role: Principal Investigator
$2,445,371 - June 2022–March 2026
Lipid Mediated Oral Tolerance
NIH
Role: Co-Principal Investigator
$2,422,174 - September 2021–March 2026
The role of neutrophils in the age-driven decline in anti-pneumococcal vaccine responses
NIH
Role: Co-Investigator
$2,634,726 - April 2022–March 2025
Developing a Multivalent Particle Vaccine Against TB
NIH
Role: Co-Investigator
$3,269,992 - July 2021–June 2023
The Translational Response of C. neoformans to Oxidative Stress and Macrophage Phagocytosis
NIH
Role: Co-Investigator
$447,863 - May 2020–April 2023
Antibody Fragments as Biochemical Tools to Interrogate CD9 Function in Inflammatory Diseases
NIH/NIGMS
Role: Co-Principal Investigator - June 2017–June 2020
Dysregulation of regulatory T cells during chronic infection in muscle
NIH
Role: Principal Investigator - November 2013–November 2016
Deciphering the mechanism of how GATA3 controls the fate of regulatory T cells at mucosal sites
Crohn‘s and Colitis Foundation of America
Role: Principal Investigator
$268,500
Journal Articles:
- Jin RM, Warunek J, Wohlfert EA. (2018) Chronic infection stunts macrophage heterogeneity and disrupts immune-mediated myogenesis. JCI insight (Sep), 3(18) doi:10.1172/jci.insight.121549
- Jin RM, Warunek J, Wohlfert EA. (2018) Therapeutic administration of IL-10 and amphiregulin alleviates chronic skeletal muscle inflammation and damage induced by infection. ImmunoHorizons (May), 2(5): 142-154. doi:10.4049/immunohorizons.1800024
- Wohlfert EA, Blader IJ, Wilson EH. (2017) Brains and Brawn: Toxoplasma Infections of the Central Nervous System and Skeletal Muscle. Trends Parasitol (Jan), 33(7): 519-531.
- Wohlfert EA, Grainger JR, Bouladoux N, Konkel JE, Oldenhove G, Ribeiro CH, Hall JA, Yagi R, Naik S, Bhairavabhotla R, Paul WE, Bosselut R, Wei G, Zhao K, Oukka M, Zhu J, Belkaid Y. (2011) GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice. J Clin Invest (Nov), 121(11): 4503-4515.
- Warunek J, Jin RM, Blair SJ, Garis M, Marzullo B, Wohlfert EA. (2021) Tbet Expression by Regulatory T Cells Is Needed to Protect against Th1-Mediated Immunopathology during Toxoplasma Infection in Mice. ImmunoHorizons (Dec), 5(12): 931-943.
- Nguyen NH, Glassman FY, Dingman RK, Shenoy GN, Wohlfert EA, Kay JG, Bankert RB, Balu-Iyer SV. (2021) Rational design of a nanoparticle platform for oral prophylactic immunotherapy to prevent immunogenicity of therapeutic proteins. Scientific reports (Sep), 11(1): 17853. doi:10.1038/s41598-021-97333-0
- Glausen TG, Carrillo GL, Jin RM, Boyle JP, Saeij JPJ, Wohlfert EA, Fox MA, Blader IJ. (2021) The Toxoplasma Polymorphic Effector GRA15 Mediates Seizure Induction by Modulating Interleukin-1 Signaling in the Brain. mBio (Jun), 12(3): e0133121. doi:10.1128/mBio.01331-21
- Kalem MC, Humby MS, Wohlfert EA, Jacobs A, Panepinto JC. (2021) Cryptococcus neoformans Coinfection Dampens the TNF-a Response in HIV-1-Infected Human THP-1 Macrophages. mSphere (Mar), 6(2).
- Carrillo GL, Ballard VA, Glausen T, Boone Z, Teamer J, Hinkson CL, Wohlfert EA, Blader IJ, Fox MA. (2020) Toxoplasma infection induces microglia-neuron contact and the loss of perisomatic inhibitory synapses. Glia (Oct), 68(10): 1968-1986. doi:10.1002/glia.23816
- Huang WC, Zhou S, He X, Chiem K, Mabrouk MT, Nissly RH, Bird IM, Strauss M, Sambhara S, Ortega J, Wohlfert EA, Martinez-Sobrido L, Kuchipudi SV, Davidson BA, Lovell JF. (2020) SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination. Adv Mater (Oct)2005637-2005637.
- Tchalla EYI, Bhalla M, Wohlfert EA, Bou Ghanem EN. (2020) Neutrophils are required during immunization with the pneumococcal conjugate vaccine for protective antibody responses and host defense against infection. J Infect Dis (May).
- Bloom ALM, Jin RM, Leipheimer J, Bard JE, Yergeau D, Wohlfert EA, Panepinto JC. (2019) Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming. Nat Commun (Oct), 10(1): 4950-4950.
- Carpenter AC, Wohlfert E, Chopp LB, Vacchio MS, Nie J, Zhao Y, Shetty J, Xiao Q, Deng C, Tran B, Cam M, Gaida MM, Belkaid Y, Bosselut R. (2017) Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF. Journal of immunology (Baltimore, Md. : 1950) (Sep), 199(5): 1716-1728. doi:10.4049/jimmunol.1700181
- Jin RM, Blair SJ, Warunek J, Heffner RR, Blader IJ, Wohlfert EA. (2017) Regulatory T Cells Promote Myositis and Muscle Damage in Toxoplasma gondii Infection. J Immunol (Jan), 198(1): 352-362.
- Wohlfert EA, Russell MW. (2016) Mucosal surfaces: immunological protection. eLS (Feb).
- Wohlfert EA, Carpenter AC, Belkaid Y, Bosselut R. (2016) In Vitro Analyses of T Cell Effector Differentiation. Methods in molecular biology (Clifton, N.J.) (Jan), 1323: 117-28.
- Rodriguez-Peña AB, Gomez-Rodriguez J, Kortum RL, Palmer DC, Yu Z, Guittard GC, Wohlfert EA, Silver PB, Misplon JA, Sommers CL, Feigenbaum L, Epstein SL, Caspi RR, Belkaid Y, Restifo NP, Samelson LE, Balagopalan L. (2015) Enhanced T-cell activation and differentiation in lymphocytes from transgenic mice expressing ubiquitination-resistant 2KR LAT molecules. Gene therapy (Oct), 22(10): 781-92. doi:10.1038/gt.2015.48
- Carson WF, Guernsey LA, Singh A, Secor ER, Wohlfert EA, Clark RB, Schramm CM, Kunkel SL, Thrall RS. (2015) Cbl-b Deficiency in Mice Results in Exacerbation of Acute and Chronic Stages of Allergic Asthma. Frontiers in immunology (Jan), 6: 592. doi:10.3389/fimmu.2015.00592
- Vacchio MS, Wang L, Bouladoux N, Carpenter AC, Xiong Y, Williams LC, Wohlfert E, Song KD, Belkaid Y, Love PE, Bosselut R, Wohlfert EA. (2014) A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells. Nat Immunol (Oct), 15(10): 947-956.
- Schiering C, Krausgruber T, Chomka A, Fröhlich A, Adelmann K, Wohlfert EA, Pott J, Griseri T, Bollrath J, Hegazy AN, Harrison OJ, Owens BM, Löhning M, Belkaid Y, Fallon PG, Powrie F. (2014) The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature (Sep), 513(7519): 564-568.
- Steward-Tharp SM, Laurence A, Kanno Y, Kotlyar A, Villarino AV, Sciume G, Kuchen S, Resch W, Wohlfert EA, Jiang K, Hirahara K, Vahedi G, Sun HW, Feigenbaum L, Milner JD, Holland SM, Casellas R, Powrie F, O'Shea JJ. (2014) A mouse model of HIES reveals pro- and anti-inflammatory functions of STAT3. Blood (May), 123(19): 2978-2987.
- Gomez-Rodriguez J, Wohlfert EA, Handon R, Meylan F, Wu JZ, Anderson SM, Kirby MR, Belkaid Y, Schwartzberg PL. (2014) Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells. J Exp Med (Mar), 211(3): 529-543.
- Grainger JR, Wohlfert EA, Fuss IJ, Bouladoux N, Askenase MH, Legrand F, Koo LY, Brenchley JM, Fraser ID, Belkaid Y. (2013) Inflammatory monocytes regulate pathologic responses to commensals during acute gastrointestinal infection. Nat Med (Jun), 19(6): 713-721.
- Sommers CL, Rouquette-Jazdanian AK, Robles AI, Kortum RL, Merrill RK, Li W, Nath N, Wohlfert E, Sixt KM, Belkaid Y, Samelson LE. (2013) miRNA signature of mouse helper T cell hyper-proliferation. PloS one (Jan), 8(6): e66709. doi:10.1371/journal.pone.0066709
- Hall JA, Cannons JL, Grainger JR, Dos Santos LM, Hand TW, Naik S, Wohlfert EA, Chou DB, Oldenhove G, Robinson M, Grigg ME, Kastenmayer R, Schwartzberg PL, Belkaid Y. (2011) Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity (Mar), 34(3): 435-447.
- Wohlfert E, Belkaid Y. (2010) Plasticity of T reg at infected sites. Mucosal immunology (May), 3(3): 213-5. doi:10.1038/mi.2010.11
- Thornton AM, Korty PE, Tran DQ, Wohlfert EA, Murray PE, Belkaid Y, Shevach EM. (2010) Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. Journal of immunology (Baltimore, Md. : 1950) (Apr), 184(7): 3433-41. doi:10.4049/jimmunol.0904028
- Oldenhove G, Bouladoux N, Wohlfert EA, Hall JA, Chou D, Dos Santos L, O'Brien S, Blank R, Lamb E, Natarajan S, Kastenmayer R, Hunter C, Grigg ME, Belkaid Y. (2009) Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity (Nov), 31(5): 772-786.
- Wohlfert E, Belkaid Y. (2008) Role of endogenous and induced regulatory T cells during infections. Journal of clinical immunology (Nov), 28(6): 707-15. doi:10.1007/s10875-008-9248-6
- Hall JA, Bouladoux N, Sun CM, Wohlfert EA, Blank RB, Zhu Q, Grigg ME, Berzofsky JA, Belkaid Y. (2008) Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity (Oct), 29(4): 637-649.
- Wohlfert EA, Nichols FC, Nevius E, Clark RB. (2007) Peroxisome proliferator-activated receptor gamma (PPARgamma) and immunoregulation: enhancement of regulatory T cells through PPARgamma-dependent and -independent mechanisms. J Immunol (Apr), 178(7): 4129-4135.
- Wohlfert EA, Clark RB. (2007) Trends in immunology (Apr), 28(4): 154-60.
- Callahan MK, Wohlfert EA, Ménoret A, Srivastava PK. (2006) Heat shock up-regulates lmp2 and lmp7 and enhances presentation of immunoproteasome-dependent epitopes. Journal of immunology (Baltimore, Md. : 1950) (Dec), 177(12): 8393-9.
- Wohlfert EA, Gorelik L, Mittler R, Flavell RA, Clark RB. (2006) Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo. J Immunol (Feb), 176(3): 1316-1320.
- Wohlfert EA, Callahan MK, Clark RB. (2004) Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice. J Immunol (Jul), 173(2): 1059-1065.
Abstracts:
- (2020) Tbet-expressing Tregs protect against lethal immunopathology during T. gondii infection. Immunology 2020. (May), (864) Poster; Oral
- Warunek, J, Jin, R.M., and Wohlfert, E.A. (2019) Tbet+ Tregs protect against lethal immunopathology during T. gondii infection. 2019 New York Upstate Immunology Conference. Cooperstown, New York (Oct) Oral
- Jordan Warunek, Richard M Jin, Brandon Marzullo and Elizabeth A Wohlfert. (2018) Tbet+ Tregs protect against lethal immunopathology during T. gondii infection. Immunology 2018. Austin, Texas (May) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2017) Pathogenic regulatory T cells promote immunopathology during infectious myositis. 2017 American Physician Scientist Association Northeast Regional Meeting. Rochester, New York (Oct) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and EA Wohlfert. (2017) Evaluation of immune mediated myogenesis during chronic infection with T. gondii. Keystone Symposium on Mononuclear Phagocytes in Health, Immune Defense and Disease. Austin, Texas (May) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2016) Pathogenic regulatory T cells promote immunopathology during infectious myositis. American Physician Scientist Association Northeast Regional Meeting. Buffalo, New York (Oct) Poster; Oral
- Blair, S.J., Grainger, J., Bouladoux, N., Urban, J., and E.A. Wohlfert. (2016) Gata3 expression by Tregs is required for mounting a Th2 immune response to the helminth gastrointestinal infection of H. polygyrus. Mucosal Immunology Course and Symposium. Toronto, (Jul) Oral
- Iluore, J.O., Jin, R.M*., Blair, S.J., Schiavoni, E., and EA Wohlfert. (2016) Infection Induced Thymic Atrophy affects development of T Regulatory Cells. University at Buffalo Annual Research Day. Buffalo, New York (Jun) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2016) Pathogenic regulatory T cells promote immunopathology during infectious myositis. 28th Annual Conference on Microbial Pathogenesis. Buffalo, New York (May) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2016) Pathogenic regulatory T cells promote immunopathology during infectious myositis. Immunology 2016. Seattle, Washington (May) Poster; Oral
- Jin, R.M, Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2016) Dysregulation of tissue-reparative regulatory T cell function in infectious myositis. 12th Annual American Physician Scientists Association Meeting. Chicago, Illinois (Apr) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2016) Pathogenic regulatory T cells promote immunopathology during infectious myositis. 16th Annual Woods Hole Immunoparasitology Meeting. Woods Hole, Massachusetts (Apr) Poster; Oral
- Jin, R.M., Blair, S.J., Blader, I.J., and E.A. Wohlfert. (2015) Getting the balance right: Immunoregulation of host-defense and tissue repair in skeletal muscle during T. gondii infection. 1st Annual Immune Imaging Symposium. Rochester, New York (Nov) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2015) Getting the balance right: Immunoregulation of host-defense and tissue repair in skeletal muscle during T. gondii infection. 2015 American Physician Scientist Association Northeast Regional Meeting. Syracuse, New York (Oct) Poster
- Jin, R.M., Blair, S.J., Heffner, R.R., Blader, I.J., and E.A. Wohlfert. (2015) Getting the balance right: Immunoregulation of host-defense and tissue repair in skeletal muscle during T. gondii infection. 18th Annual New York Upstate Immunology Conference. Bolton Landing, New York (Oct) Poster
- Schiavoni, E., Blair, S.J., Jin, R.M., Iluore, J.O., and E.A. Wohlfert. (2015) The Development of T Regulatory Cells During Toxoplasma gondii Infection Induced Thymic Atrophy. 18th Annual New York Upstate Immunology Conference. Bolton Landing, New York (Oct) Poster
- Blair, S.J., Iluore, J.O., Jin, R.M. and E.A. Wohlfert. (2015) The Development of T Regulatory Cells During Toxoplasma gondii Infection Induced Thymic Atrophy. Buffalo Immunology Conference. Chautauqua, New York (Mar) Poster
- Jin, R.M., Blair, S.J., Blader, I.J., and E.A. Wohlfert. (2015) Tissue-specific immunoregulation of skeletal muscle during chronic T. gondii infection. Buffalo Immunology Conference. Chautauqua, New York (Mar) Poster
Professional Memberships:
- American Association of Immunologists (2016–present)
Presentations:
- "Muscling through Chronic Infection" Skeletal Muscle Stem Cells and Regeneration, FASEB Summer Research Conference (2022)
- "Muscling through Chronic Infection" Host-Pathogen Invited Speaker Series, UC Riverside (2021)
- "Infection Induced Pathogenic Tregs and the consequences on tissue repair during chronic muscle infection" Mechanisms of Parasitism Seminar Series, Immunology Program, University of Iowa (2018)
- "Pathogenic Tregs promote myositis during skeletal muscle Infection" British Society of Immunology Manchester University, Department of Immunology (2016)
- "Regulatory Affairs of Gata3" American Academy of Allergy, Asthma and Immunology Annual Meeting (2016)
- "Tregs impair tissue repair program in skeletal muscle during Infection" Department of Immunology Seminar Series (2015)
- "Dynamics of Regulatory T cells throughout infection: What happens Next" Upstate Immunology Conference Annual Meeting (2015)
- "Dynamics of Tregs during Infection" University at Buffalo Department of Oral Biology (2014)
- "Stability and Function of Tregs during inflammation; They just GATA have it" Buffalo Immunology Conference (2014)
- "Transcription Factor Networks Control Regulatory T cell Stability and Function During Inflammation" University at Buffalo Department of Biochemistry (2014)
- "Transcription Factor Networks Control Regulatory T Cell Stability and Function During Inflammation" Uniformed Services University, School of Medicine, Department of Medicine (2013)
Service Activities:
- PTHE, CSR; ad hoc reviewer (2022)
- Faculty Search Committee; Chair (2022–present)
- ; Director of Graduate Studies (2022–present)
- ZRG1 Member conflict panel, CSR; ad hoc (2022)
- Faculty Senate Subcommittee on Child and Eldercare (2021–present)
- ; Elected Representative (2021–present)
- ; Associate Director of Graduate Studies (2021–2022)
- ZRG Member Conflict, CSR; Ad hoc reviewer (2021)
- Agence Nationale de la Recherche, Paris, France (2021)
- American Association of Immunologists, Abstract Programming Committee; Abstract Programming Committee (2019–present)
- UB Collegiate Science & Technology Entry Program Research Symposium (2019–present)
- National Medical Research Council, Ministry of Health, Singapore; National Medical Research Council (2019)
- Immunity and Host Defense, CSR; Early Career Reviewer (2017)
- Medical Research Council, Infections and Immunity Board (2017)
- MD/PhD Admissions Committee (2016–2018)
- Redesigned the departmental curriculum for the graduate students; Curriculum Review Committee (2013–2014)
- New York Immunology Conference, Scientific Advisory Board member; Member (2013–present)
- New York Upstate Immunology Conference; Scientific Advisory Board member (2013–present)
- ; Graduate Affairs Committee Member (2013–2018)
- J Leuk Biol, J Immunol, Nat Communications, Immunol Invest, Plos Path, Plos One, Cytokine, Front Immunol, Front Cell Inf Micro, Nat Com Bio, Scientific Reports, American J Path; Reviewer (2012–present)