Phone (Lab): 704.687.8507
Office: Woodward 386A
POSITIONS AND HONORS
1990-1993: Science and Engineering Research Council (UK), Overseas Research Scholarship
1993-1995: Tulane University Chancellor’s Fellowship.
1995-1996: American Heart Association Graduate Student Research Fellowship
1996-1998: Research Associate, Department of Microbiology and Immunology, Tulane University
1998: Leah Seidman Schaffer Award for Excellence in Postdoctoral Research, Tulane University
1998: Chancellor’s Award for Excellence in Research by a Postdoctoral Fellow, Tulane University
1998-2000: Research Assistant Professor, Department of Biology, UNC Charlotte
1999-present: Regular Member, American Association of Immunologists
2000-2004: Assistant Professor, Department of Biology, UNC Charlotte
2002: American Association of Immunologists Pfizer-Showell Travel Award for Early-Career Scientists
2002-2006: Editorial Board Member, Journal of Immunology
2003: American Association of Immunologists Junior Faculty Travel Award.
2004-2008: Associate Professor, Department of Biology, Univ. North Carolina at Charlotte, NC
2008-present: Professor, Department of Biology, Univ. North Carolina at Charlotte, NC
2011-present: Editor-in-Chief, Frontiers in Microbial Immunology
2012-2013: Chair, College Faculty Development Awards Committee, UNCC
2013: Chair, Departmental Chair Comprehensive Review Committee, UNCC
2013-2014: Chair, Biology Departmental Review Committee, UNCC
2013-2014: Vice-Chair, College Review Committee, UNCC
2016-present: Chartered Member, NIH CSR Brain Disorders and Clinical Neuroscience (CNBT) study section
2016-present: Vice Chair for Research, Department of Biological Sciences
2017: UNCC College of Liberal Arts and Sciences Award for the Integration of Undergraduate Teaching and Research
2017-present: Writing Coach, “Catalyst” College Professional Development and Mentoring Program
The role of the neuropeptide substance P in microbe-induced CNS inflammation
Substance P, mediates a variety of biological effects via high affinity receptors for this neuropeptide (termed neurokinin-1 receptors: NK-1R). As such, NK-1R antagonists have been subjected to extensive research for use in the treatment of a variety of disease conditions, and several of these agents have recently been introduced clinically to prevent nausea and vomiting. Importantly, our laboratory has assembled a compelling body of evidence indicating that substance P/NK-1R interactions exacerbate inflammation at mucosal sites and within the CNS. In addition to its effects on leukocytes, we have demonstrated that substance P exacerbates the inflammatory responses of resident brain cells including microglia and astrocytes to clinically relevant bacterial pathogens. Furthermore, we have also shown that endogenous substance P/NK-1R interactions are required for maximal inflammation and CNS damage in murine models of meningitis. Interestingly, our data indicate that prophylactic or therapeutic systemic administration of an NK-1R antagonist can markedly attenuate bacterially-induced neuroinflammation in animal models. As such, these data suggest that the NK-1R may represent an important new target in the treatment of potentially lethal CNS inflammation.
Glia utilize cell surface and cytosolic innate immune receptors to recognize microbial and viral pathogens
Glial cells such as microglia and astrocytes are increasingly recognized to play a critical role in the initiation, progression, and/or maintenance of inflammatory host responses to CNS pathogens. Our laboratory has been at the forefront in the study of the mechanisms by which these cells perceive viral and bacterial pathogens. The innate immune system recognizes a wide spectrum of pathogens without the need for prior exposure and the identification of highly conserved families of proteins that serve as microbial pattern recognition receptors including the Toll-like (TLR), nucleotide-binding oligomerization domain-like (NLR), and retinoic acid inducible gene-I-like (RLR) receptors has shed light on the mechanisms by which this is accomplished. These microbial sensors precipitate the production of inflammatory cytokines and antiviral type I interferons. Hence, activation of cells in this manner can initiate the repertoire of defense mechanisms used by the innate immune system. We have shown that microglia and astrocytes express cell surface TLRs and use cytosolic sensors for the detection of intracellular pathogens that include NOD2, an intracellular receptor for bacterial peptidoglycans, and two members of the RLR family, RIG-I and MDA5, that serve as cytosolic sensors for replicative RNA viruses. Furthermore, we have subsequently described the expression of two cytosolic sensors for double-stranded DNA by glia, DNA-dependent activator of interferon-regulatory factors (DAI) and cyclic GMP-AMP synthase (cGAS), suggesting that these novel sensors might play a critical role in the detection of replicative DNA viruses by CNS cells.
Current Project Support:
1R03 NS097840 PI: Marriott, 03/01/17-02/28/20 “Role of DAI in viral CNS infection: A pilot study”
CURRENT LAB MEMBERS
Brittany Johnson, Ph.D.
Austin Jeffries, Ph.D. Candidate
Alexander Suptela, Graduate Student