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Terry                          Connell

Terry D. Connell PhD

Department of Microbiology and Immunology

Professor of Microbiology and Immunology, Adjunct Professor of Oral Biology

Specialty/Research Focus

Allergy and Immunology; Gene Expression; Genomics and proteomics; Immunology; Infectious Disease; Medical Microbiology; Microbial Pathogenesis; Microbiology; Molecular and Cellular Biology; Molecular Basis of Disease; Molecular genetics; Signal Transduction

 
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Professional Summary:

My laboratory researches complementary aspects of host-pathogen interactions through two distinct projects in the fields of immunology and bacterial pathogenesis.

In the field of immunology, we study the cellular and molecular mechanisms that regulate mucosal immune responses by stimulating the immune system with enterotoxins produced by certain strains of E. coli. Mucosal immune responses provide critical protection against microbial pathogens that invade through the body’s mucosal surfaces (the gut, the oral cavity, the urogenital system, and the respiratory system). The enterotoxins we employ are potent mucosal adjuvants which enhance mucosal and systemic immune responses to foreign antigens when administered concurrently. In addition to describing these immune regulation mechanisms that respond to the enterotoxins, our research can also support the development of new mucosal vaccines.

In the field of bacterial pathogensis, our research analyzes the genetic factors in four pathogenic species of the Bordetellae that enable these microorganisms to scavenge iron from host tissues. The ability of these bacterial pathogens to infect a host depends upon the bacteria acquiring iron from that host using receptors and accessory proteins encoded by specific gene clusters, including hurIR-bhuRSTUV and ecfIR-bfrH. Extracellular signals control expression of these gene clusters by regulating specific sigma factors (ECF). Information obtained in these experiments will provide the means to create drugs to abrogate acquisition of iron, an essential nutrient, and identification of new antigens that can be employed as vaccine targets.

Education and Training:
  • PhD, University of North Carolina, Chapel Hill (1989)
  • MS, University of Alabama (1981)
  • BS, University of Alabama (1977)
Employment:
  • Professor, University at Buffalo, SUNY (2007-present)
  • Associate Professor, SUNY Buffalo (1999–2007)
  • Assistant Professor, SUNY Buffalo (1993–1999)
  • Research Associate, Uniformed Services University of the Health Sciences (1992–1993)
  • Instructor, Uniformed Services University of the Health Sciences (1991–1992)
  • Postdoctoral Fellow, Uniformed Services University of the Health Sciences (1989–1992)
  • Laboratory Instructor, University of North Carolina (1984–1985)
  • Research Technician, University of Utah (1981–1983)
  • Teaching Assistant, University of Utah (1980)
  • Laboratory Instructor, University of Alabama (1977–1979)
  • Technical Collaborator, University of Alabama (1976–1977)
See All (11 Total) >
Awards and Honors:
  • Dean‘s Award, Univ. 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 of Buffalo, Recognition as a UB Top 100 Federal Grantee (2005)
  • Certificate of Recognition for Dedication to Students, University at Bflo (2005)
  • University of 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 GENETICS OF IRON ACQUISITION IN THE BORDETELLAE: One focus of my laboratory is to investigate the mechanisms by which Bordetella pertussis, B. bronchiseptica, and B. avium, three gram-negative bacteria that infect the upper respiratory tract of children and domesticated animals, acquire essential nutrients required to colonize the respiratory tract and to sustain progressive infections. Iron (Fe) is one of the most important nutrients required by most, if not all infectious bacteria which must be obtained from the tissues and fluids of the infected host. Using proteomic, recombinant, immunological, and biochemical methods, we are unraveling the genetic and molecular components of these bacteria that mediate acquisition of Fe from host-derived heme, myoglobin, and hemoglobin. We have identified a cluster of genes (bhuRSTUV) which encodes five proteins required for uptake of heme and a second gene cluster (rhuIR) which encodes for two heme-dependent regulatory proteins which control heme-dependent expression of the uptake systems`. Our current research is focused on analysis of these seven genes and expressed proteins.
  • Bacterial Pathogenesis
  • Molecular and cellular immunology
  • Mucosal Immunology: CELLULAR AND MOLECULAR REGULATION OF MUCOSAL IMMUNE RESPONSES: Another major focus of my laboratory is to investigate the cellular and molecular events which modulate mucosal immune responses. We have demonstrated that LT-IIa and LT-IIb, two Type II heat-labile enterotoxins of Escherichia coli, are potent oral and nasal immunogens that have the capacity for augmenting humoral and cellular immune responses. Using a variety of immunological and cellular techniques (including flow cytometry, FRET fluorescent detection, cytokine multiplex analysis, mutagenesis, and the use of transgenic mice), we are evaluating the manners in which these two immunomodulators productively interact with various lymphoid cells such as T cells, B cells, and dendritic cells to induce or suppress cytokine production, co-stimulatory ligand expression, and proliferation. A practical outgrowth of these experiments is the potential to engineer novel recombinant vaccines by genetically fusing antigens from different pathogens to the immunomodulatory enterotoxins. We have shown that upon nasal immunization, these genetically-fused proteins elicit protective immune responses in animal challenge models. Other fusion proteins being produced are incorporating antigens from Haemophilus influenzae, hepatitis virus, and tuberculosis in an effort to produce new and effective vaccines.
Grants and Sponsored Research:
  • 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 1991–January 1996
    Training Program in Periodontal Disease , NIDR
    National Institute for Dental & Craniofacial Research
    Role: Contributor
    $1,165,033
See All (12 Total) >
Patents:
  • 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 (61 Total) >
Abstracts:
  • Martin, M., Hajishengallis, G., Michael Russell, Metzger, D., Terry Connell, Michalek, S.M.. Purification of the recombinant protein SBR-LT-IIa2/B. J. Dent. Res.. 1998; 77(A).
Books and Book Chapters:
  • Holmes, RK, MJ Jobling and TD Connell. Cholera toxin and related heat-labile enterotoxins of Gram-negative bacteria.. 1995; 8.

Professional Memberships:
  • American Association for the Advancement of Science (1996)
  • American Society for Microbiology (1996)
  • Center for Advanced Molecular Biology and Immunology (1996)
  • Witebsky Center for Microbial Pathogenesis and Immunology (1996)
  • Buffalo Collegium of Immunology (1996)
  • UB Microbial Pathogenesis Graduate Group (1996)
  • Oral Immunology/Microbiology Graduate Group (1996)
  • Society for Mucosal Immunology (1996)
  • American Association of Immunologists
  • International Institute of Biomedical Sciences and Technology
Presentations:
  • "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 (23 Total) >
Service Activities:
  • Microbiology; Reviewer (ad hoc); Ad Hoc Reviewer (2003)
  • Microbiology; Reviewer (ad hoc); Ad Hoc Reviewer (2003)
  • President, WNYASM; Western New York Branch of the American Society of Microbiology; President (2002–2003)
  • Immunological Investigations; Ad Hoc Reviewer (2000)
  • Journal of Bacteriology; Ad Hoc Reviewer (1999–2000)
  • BioTechniques; Ad Hoc Reviewer (1999)
  • Gene; Ad Hoc Reviewer (1997)
  • Newsletter Editor, WNYASM; Ad Hoc Reviewer (1994–1996)
  • Infection and Immunity, Editorial Board; Reviewer (1994)
  • Microbial Pathogenesis; Ad Hoc Reviewer (1992)

Clinical Specialties:
Clinical Offices:
Insurance Accepted:

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Contact Information

147 Biomedical Research Building
3435 Main St.
Buffalo, NY 14214
Phone: (716) 829-3364
Fax: (716) 829-2158
Email: connell@buffalo.edu


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