Terry D. Connell PhD

Terry Connell

Terry D. Connell
PhD

Professor of Microbiology and Immunology, Adjunct Professor of Oral Biology

Department of Microbiology and Immunology

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Allergy and Immunology; Apoptosis and cell death; Bacterial Pathogenesis; Gene Expression; Genomics and proteomics; Immunology; Infectious Disease; Medical Microbiology; Microbial Pathogenesis; Microbiology; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Protein Function and Structure; Signal Transduction

Contact Information
Rm 5114
955 Main St, JSMBS
Buffalo, New York 14203
Phone: (716) 829-3364
Fax: (716) 829-2158
connell@buffalo.edu



Professional Summary:

Research efforts in my laboratory are focused in the fields of immunology and bacterial pathogenesis, two diverse fields of biomedical research for which I have two separate research groups. Projects in both fields are performed by undergraduates, doctoral and master’s degree students, postdoctoral fellows and senior research associates.

One major focus of my laboratory is studying the regulation of mucosal immune responses. We investigate the cellular and molecular events by which Type II heat-labile enterotoxins (HLTs), produced by certain strains of Escherichia coli, modulate immune responses. We have demonstrated that LT-Ila, LT-IIb and LT-IIc, when co-administered with an antigen, have the capacity to enhance antibody and cellular immune responses to that antigen. Using a variety of immunological and cellular technologies, including flow cytometry, fluorescence resonance energy transfer (FRET) detection, cytokine multiplex analysis, mutagenesis, quantitative Reverse Transcription PCR (qRT-PCR), RNA-sequencing (RNA-Seq) and a variety of transgenic mice, we are investigating the mechanisms by which these immunomodulators productively interact with various immunocompetent cells (T cells, B cells, dendritic cells, macrophages) to induce or suppress cytokine production, costimulatory ligand expression and cellular proliferation. A practical outgrowth of these experiments is the potential to engineer novel recombinant vaccines by genetically fusing antigens from different pathogens to the enterotoxins. Recent experiments have shown that these HLT are lethal for triple-negative breast cancer cells, which has opened a new area of oncological research for the lab.

A second focus of my laboratory is to investigate the cytotoxic activities of the type II heat-labile enterotoxins for triple-negative breast cancer cells. Treatment of both cancer cell lines and primary cancer cells obtained from human tumors with LT-IIc elicits unusual vacuolation in the cells, enhanced autophagy, stalled autophagic flux, apoptosis, and necroptosis. Our laboratory is engaged in identifing the cellular mechanisms underlying those activities of LT-IIc with the goal of investigating those cytotoxic pathways to develop new pharmacological agents to treat triple-negative breast cancer, a type of cancer with poor prognosis and few treatment options.

In the last five years, we have evaluated the capacity of LT-IIc to specifically kill triple-negative breast cancer cells without having an effect on non-cancerous breast epithelial cells. This cytotoxic activity is induced in both TNBC cell lines and in breast cancer cells isolated from primary human tumors. Recently, we have demonstrated that binding of the toxin to its receptors on the cancer cell surface is sufficient to induce cytotoxicity. Currently, we are focused on identifying those receptors.

Education and Training:

  • PhD, University of North Carolina, Chapel Hill (1989)
  • MS, University of Alabama (1981)
  • BS, University of Alabama (1977)

Employment:

  • Professor, Microbiology and Immunology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (2007-present)
  • Associate Professor, Microbiology and Immunology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (1999–2007)
  • Assistant Professor, Microbiology and Immunology, University at Buffalo Jacobs School of Medicine & Biomedical Sciences (1993–1999)
  • Research Associate, Microbiology and Immunology, Uniformed Services University of the Health Sciences (1992–1993)
  • Instructor, Microbiology and Immunology, Uniformed Services University of the Health Sciences (1991–1992)
  • Postdoctoral Fellow, Microbiology and Immunology, Uniformed Services University of the Health Sciences (1989–1992)
  • Laboratory Instructor, Microbiology and Immunology, University of North Carolina (1984–1985)
  • Research Technician, Biological Sciences, University of Utah (1981–1983)
  • Teaching Assistant, Biological Sciences, University of Utah (1980)
  • Laboratory Instructor, Biological Sciences, University of Alabama (1977–1979)
  • Technical Collaborator, Biological Sciences, University of Alabama (1976–1977)
See all (1 more)

Awards and Honors:

  • Dean‘s Award, University at Buffalo School of Medicine and Biomedical Sciences (2012)
  • Individual Development Award, United University Professions (2008)
  • Nat'l Inst. of Dental & Craniofacial Research, Independent Scientist Award (2006)
  • Inventor of the Year, Life Sciences (2006)
  • Individual Development Award, United University Professions (2005)
  • University at Buffalo, Recognition as a UB Top 100 Federal Grantee (2005)
  • Certificate of Recognition for Dedication to Students, University at Buffalo (2005)
  • University at Buffalo, Recognition as a UB Top 100 Federal Grantee (2002)
  • Individual Development Award, United University Professions (1999)
  • Term Faculty Development Award, NY State/United University Professions (1995)
  • National Research Service Award Traineeship (1989)
  • Graduate Council Fellowship, University of Alabama (1978)

Research Expertise:

  • Bacterial genetics: Molecular biology underlying the capacity of AIEC strain of Escherichia coli to induce Crohn's Disease and inflammation in the intestinal tract.
  • Bacterial pathogenesis: Pathogenesis of the bacterial heat-labile enterotoxins.
  • Cancer cell biology: Use of bacterial products to target human cancer cells
  • Immunobiology: Cellular and molecular biology of immunomodulation modulated by dendritic cells, T cells, B cells, neutrophils, and other immune cells.
  • Molecular and cellular immunology
  • Mucosal immunology: Cellular and molecular events which modulate mucosal immune responses
  • Vaccine development: Use of bacterial heat-labile enterotoxins as adjuvants in the design of new and improved vaccines against pathogens, toxins, and other biological agents.

Research Centers:

  • Witebsky Center for Microbial Pathogenesis and Immunology

UB 2020 Strategic Strengths:

  • Molecular Recognition in Biological Systems and Bioinformatics

Grants and Sponsored Research:

  • April 2020–March 2022
    Identification of new ribosylation-dependent immunoregulatory factors
    The National Institute of Allergy and Infectious Disease, NIH
    Role: Principal Investigator
  • July 2015–January 2021
    Oral immunity and adjuvant receptors
    The National Institute of Dental and Craniofacial Research, NIH
    Role: Co-Principal Investigator
  • April 2018–March 2020
    Evaluation of a Specific Cytotoxic Agent and Identification of a New Targetable Receptor for Human TripleNegative Breast Cancer
    Dept. of Defense, BCRP, Breakthrough Award Levels 1
    Role: Co-Investigator
    $375,000
  • April 2017–March 2019
    Specific induction of lethal autophagy in triple-negative breast cancer cells
    National Cancer Institute, NIH
    Role: Principal Investigator
    $275,000
  • August 2015–March 2018
    Safe Mucosal Adjuvants
    The National Institute of Dental and Craniofacial Research, NIH
    Role: Principal Investigator
  • August 2010–December 2015
    Development of a chimeric protein a a novel multivalent delivery vehicle for inducing protective immune respones to pathogens on mucosal surfaces
    The John R. Oishei Foundation
    Role: Principal Investigator
  • January 2010–August 2013
    Development of a chimeric protein as a novel multivalent delivery vehicle for inducing protective immune responses to pathogens on mucosal surfaces
    The Oishei Foundation
    Role: Principal Investigator
    $195,120
  • August 2006–July 2011
    Type II enterotoxins as mucosal immunomodulators
    National Institutes of Health
    Role: Principal Investigator
    $1,150,000
  • January 2004–December 2008
    Antigens of Streptococcus mutans in caries immunity
    National Institute of Dental and Craniofacial Research
    Role: Co-Principal Investigator
    $936,812
  • July 2005–November 2007
    Interactions of the E. coli Type II heat-labile enterotoxins with dentritic cells
    Buswell Foundation
    Role: Contributor
    $135,000
  • December 2001–March 2007
    Type II enterotoxins as immunomodulators
    National Institute for Dental & Craniofacial Research
    Role: Principal Investigator
    $487,051
  • April 2001–March 2006
    Type II enterotoxins as mucosal immunomodulators
    National Institute for Dental & Craniofacial Research
    Role: Principal Investigator
    $789,000
  • January 1999–December 2003
    Antigens of Streptococcus mutans in caries
    NICDR
    Role: Co-Principal Investigator
    $900,000
  • June 1996–May 2002
    Extra-cellular secretion in Vibrio cholerae
    NIAID
    Role: Principal Investigator
    $350,000
  • January 2000–January 2001
    Crystallographic investigation of the Vibrio cholerae chitinase: Structural resolution of a bacterial extracellular transport signal
    State University of New York at Buffalo
    Role: Principal Investigator
    $20,000
  • January 1994–January 1999
    Lucille P. Markey Trust
    Agency for Toxic Substances and Disease Registry, CDC
    Role: Contributor
    $1,000,000
  • January 1995–January 1997
    A Recombinant Porphyromonas gingivalis vaccine
    National Institute for Dental & Craniofacial Research
    Role: Principal Investigator
    $50,000
  • January 1993–January 1996
    Extracellular secretion in Vibrio cholerae
    State University of New York at Buffalo
    $75,000
  • January 1991–January 1996
    Training Program in Periodontal Disease , NIDR
    National Institute for Dental & Craniofacial Research
    Role: Contributor
    $1,165,033
See all (9 more)

Patents:

  • “Adjuvant activities of mutants of LT-IIa and LT-IIb enterotoxin lacking binding to ganglioside GD1a” (2010)
  • “Adjuvant activities of mutants of LT-IIa and LT-IIb enterotoxin lacking binding to ganglioside GD1a” Connell, T.D., , , , (2008)
  • Chimeric antigen-enterotoxin mucosal immunogen A method for inducing immune respnses by recombinant antigen-enterotoxin chimeric mucosal immunogens that contain the A2/B subunits of cholera toxin or the type II heat-labile enterotoxins. These chimeras differentially enhance antibody secretion, cytokine production, and B7-co-stimulation of T cells and CD40L expression of CD4+ T cells. (2005)

Journal Articles:

See all (93 more)

Books and Book Chapters:

  • Holmes, RK, MJ Jobling and TD Connell. (1995) Cholera toxin and related heat-labile enterotoxins of Gram-negative bacteria. Marcel Dekker, Inc..

Abstracts:

  • Martin, M., Hajishengallis, G., Michael Russell, Metzger, D., Terry Connell, Michalek, S.M. (1998) Purification of the recombinant protein SBR-LT-IIa2/B. (Jan) 216
  • Jobling, M.G., Terry Connell, Holmes, R. K. (1990) Molecular genetic analysis of binding activity of B subunits of enterotoxins of the Vibrio cholerae/Escherichia coli family. (Jan)

Professional Memberships:

  • American Association for the Advancement of Science (1996–present)
  • American Society for Microbiology (1996–present)
  • Center for Advanced Molecular Biology and Immunology (1996–present)
  • Witebsky Center for Microbial Pathogenesis and Immunology (1996–present)
  • Buffalo Collegium of Immunology (1996–present)
  • UB Microbial Pathogenesis Graduate Group (1996–present)
  • Oral Immunology/Microbiology Graduate Group (1996–present)
  • Society for Mucosal Immunology (1996–present)
  • American Association of Immunologists
  • International Institute of Biomedical Sciences and Technology

Presentations:

  • "“Disproving a Perfectly Good Hypothesis: The initial trigger for modulating the cytotoxic activity of an understudied bacterial toxin for triple-negative breast cancer cells isn’t what we thought!”" Breast Cancer Research Group, Roswell Park Cancer Institute (2021)
  • "“Targeting triple-negative breast cancer using a ganglioside-binding microbial toxin”" Breast Cancer Research Group, Roswell Park Cancer Institute (2019)
  • "“Ongoing studies targeting triple negative breast cancer using a bacterial enterotoxin”" Breast Cancer Research Group, Roswell Park Cancer Institute (2018)
  • "Above-the-waist activities of a bacterial endotoxin. Who knew!?" Division of Infectious Disease, The University at Buffalo (2018)
  • "“Ganglioside-dependent cytotoxic activity of the type II heat-labile enterotoxin of E. coli for human triple negative breast cancer”" Glycobiology Research Group, The University at Buffalo (2018)
  • "Heme acquisition: a heme-regulated virulence determinant of the Bordetellae" Invited seminar, Georgia State University; Georgia State University; Department of Biology (2003)
  • "The role of Type II enterotoxins in mucosal adjuvant stimulation" Invited seminar, GlaxoSmithKline (Belgium); Vaccine group; GlaxoSmithKline, vaccine group (2003)
  • "A comparative analysis of the adjuvant activities of CT and the Escherichia coli Type II enterotoxins (LT-IIa, LT-IIb); a role for ganglioside-binding specificity in immunomodulation" American Society for Microbiology, 102nd General Meeting; American Society for Microbiology (2002)
  • "Inducible expression of heme/hemoglobin uptake by Bordetella spp" Dept. of Biological Sciences and The Howard Hughes Undergraduate Program, The University of Alabama (2001)
  • "Genetic regulation of heme uptake by the bacterial pathogen Bordetella avium" Department of Oral Biology, SUNYAB (2001)
  • "Regulation of heme uptake by Bordetella spp" Eleventh Annual Meeting of the Oral Immunology/Microbiology Research Group (2001)
  • "Utilization of heme by the respiratory pathogen Bordetella pertussis and B. avium is regulated by an ECR sigma factor" Center for Advanced Molecular Biology and Immunology, Faculty Research Exchange Day, SUNYAB (2000)
  • "Heme, hemoglobin, and iron: genetic analyses of an iron uptake system in the upper respiratory pathogens Bordetella avium and Bordetella pertussis" The University of Houston, Department of Biology and Biochemistry (2000)
  • "Bordetella sp. utilize heme as a source of iron for growth: a genetic analysis of the Fe-regulated frg locus" Microbial Pathogenesis Graduate Group, SUNYAB (1999)
  • "Bordetella sp. utilize heme as a source of iron for growth: a genetic analysis of the Fe-regulatef frg locus" University of Texas Medical Branch; ; Department of Microbiology and Immunology (1999)
  • "Fe-regulation in the respiratory pathogen Bordetella avium" University of Alabama, Dept. of Microbiology (1999)
  • "Secretion of cholera toxin and chitinase by Vibrio cholerae" University of Maryland; ; Division of Hospital Epidemiology (1998)
  • "The role of Fe in virulence of Bordetella avium" Center for Biologics Evaluation and Research; Food and Drug Administration (1998)
  • "The genetics of iron-uptake by the respiratory pathogen Bordetella avium" Department of Biophysical Pharmacology, SUNYAB (1998)
  • "The genetics of iron-uptake by the respiratory pathogen Bordetella avium" Department of Biology, SUNYAB (1998)
  • "Initial studies on iron uptake by the pathogen Bordetella avium" Department of BiochemistrySUNYAB (1997)
  • "Acquisition of iron by Bordetella avium" Center for Microbial Pathogenesis Monthly Seminar Series, SUNYAB (1996)
  • "Extracellular secretion by Vibrio cholerae and Ganglioside-binding of LT-II heat liable enterotoxins" Research Colloquium, Division of Infectious Disease (1996)
  • "Initial Studies of the structural signal for extracellular transport of cholera toxin and other proteins by Vibrio cholerae" 31st US/Japan Joint Conference on Cholera and related Diarrrheal Diseases (1995)
  • "A recombinant Porphyromonas gingivalis vaccine" Fifth Annual Meeting of the Oral Immunology/Microbiology Research Group (1995)
  • "Extracellular secretion of cholera toxin by Vibrio cholerae" Infectious Diseases Research Conference (1994)
  • "Genetics of receptor binding by Type II heat-labile enterotoxins" Microbial Pathogenesis Fall Research Forum of the SUNYAB Microbial Pathogenesis Graduate Group (1993)
  • "Genetic analysis of the ganglioside-binding activity of the Type II heat-labile enterotoxins of Escherichia coli" 27th US/Japan Joint Conference on Cholera and Related Diarrheal Diseases (1991)
See all (18 more)

Service Activities:

  • Applied Immunology and Disease Control (AIDC) IRG: Antimicrobial Vaccine Development. Small Business panel, National Institutes of Health; Chair (2021–present)
  • IMM-12 Microbial Vaccine Development Small Business panel, The National Institutes of Health; Chair (2021–present)
  • ZRG1 IMM-R (12), Small Business: Immune Responses and Vaccines Against Non-HIV Microbial Pathogens,, National Institutes of Health; Chair (2020–present)
  • CHAIR, ZRG1 IMM-U81, “NIH Research Enhancement Award (R15), National Institutes of Health; Chair (2019–present)
  • ZRG1 IMM-R(12), Small Business: Immune Responses and Vaccines Against Non-HIV Microbial Pathogens, National Institutes of Health, Nov. 4-5, 2019.; CHAIR and Reviewer, (2019–present)
  • Associate Graduate Director for the doctoral program in Microbiology and Immunology; Associate Graduate Director (2019–2021)
  • McNair Scholars Summer Research Internship; Mentor (2019–present)
  • ZRG1 IMM R(12), “ZRG1 IMM-R 12, Vaccines and Immune responses to Non-HIV Infections”, National Institutes of Health, Mar. 21, 2019.; VICE CHAIR (2019–present)
  • ZRG1 IMM R(12), “Non-HIV vaccines”, National Institutes of Health, November 15-16, 2018.; Vice Chair (2018–present)
  • Small Business Innovation Research (SBIR) Program, Adjuvant Discovery for Vaccines and for Allergic Diseases, National Institutes of Health; Chair (2018–present)
  • Medical School Move Committee; Departmental representative (2017–2018)
  • CLIMB Program, Fellowship Review committee; Chair (2017–2018)
  • Innovative Micro-programs Accelerating Collaboration in Themes (IMPACT), VP of Research; Reviewer (2017–present)
  • National Medical Research Council, SINGAPORE; International Expert Reviewer (2016–2020)
  • Special Emphasis Panel/SRG;; Ad Hoc Reviewer (2012)
  • IHD Immunology and Host Defense;; Ad Hoc Reviewer (2012)
  • National Medical Research Council (NMRC); International Expert Reviewer, Singapore;; Grant Reviewer (2012–2014)
  • F13 Infectious Diseases and Microbiology Fellowship Review Panel;; Ad Hoc Reviewer (2011)
  • Infectious Diseases and Microbiology Fellowship Review Panel;; Ad Hoc Reviewer (2011)
  • U.S. Civilian Research and Development Foundation (CRDF); U.S. Dept of State;; Grant Reviewer (2010)
  • The Witebsky Center for Microbial Pathogenesis and Immunology; Director (2010–2012)
  • ARRA Special Emphasis Panel;; Ad Hoc Reviewer (2009)
  • Special Emphasis Panel/Scientific Review Group; Reviewer (off site);; Grant Reviewer (2009)
  • Admissions, Interdisciplinary Graduate Program in Biomedical Sciences; Director (2009–present)
  • National Medical Research Council, Singapore; August 2008, February 2011;; Grant Reviewer (2008–2011)
  • Admissions Committee, Interdisciplinary Graduate Program; Member (2008–2009)
  • Commonwealth Universal Research Enhancement Program (CURE); Pennsylvania Dept of Health;; Grant Reviewer (2007)
  • NIH; Host Interactions with Bacterial Pathoges (HIBP); June 2006, Oct 2006, June 2008, June 2010;; Ad Hoc Reviewer (2006–2010)
  • Michael Smith Foundation for Health Research, Vancouver, BC, Canada;; Grant Reviewer (2006)
  • CSR; IDM-H, Special Emphasis Panel;; Chair (2004–2005)
  • Basic Immunology & Infectious Disease Section;; Ad Hoc Reviewer (2004)
  • Microbiology Reviewer (ad hoc); Ad Hoc Reviewer (2003–present)
  • Microbiology Reviewer (ad hoc); Ad Hoc Reviewer (2003–present)
  • NIH; SSS-K, Special Emphasis Panel;; Chair (2003–2005)
  • President, WNYASM Western New York Branch of the American Society of Microbiology; President (2002–2003)
  • NIH; GRIP, Global Health Research Initiative Program; 2002, 2004, 2006;; Grant Reviewer (2002–2006)
  • NIH; SSS-K, Special Emphasis Panel;; Grant Reviewer (2001–2003)
  • Qualifying Examination Committee; Chair (2001–present)
  • Immunological Investigations; Ad Hoc Reviewer (2000)
  • Divisional Committee; Member (2000–present)
  • Journal of Bacteriology; Ad Hoc Reviewer (1999–2000)
  • BioTechniques; Ad Hoc Reviewer (1999)
  • Medical Student Thesis Honors Committee; Member (1999–present)
  • Selection Committee, The 1998 Dean's Award for Outstanding Dissertation Research; Member (1998)
  • Gene; Ad Hoc Reviewer (1997)
  • Selection Committee, Dean's Distinguished Scientist Seminar Series Committee; Member (1996)
  • Dean's Committee for Biochemistry Course Development; Member (1996)
  • Graduate Affairs Committee; Member (1996–present)
  • USDA; USDA National Research Initiative Competitive Grants Program;; Ad Hoc Reviewer (1994–2004)
  • Infection and Immunity, Editorial Board; Reviewer (1994–present)
  • Departmental Seminar Committee; Chair (1993–1996)
  • Academic Status Committee; Member (1993–1996)
  • Curriculum Committee; Member (1993–1995)
  • Microbial Pathogenesis; Ad Hoc Reviewer (1992)
  • Special Emphasis Panel; Oral, Dental and Craniofacial Sciences;; Ad Hoc Reviewer

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Contact Information

Rm 5114
955 Main St, JSMBS
Buffalo, New York 14203
Phone: (716) 829-3364
Fax: (716) 829-2158
connell@buffalo.edu