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ACADEMIC DEGREES

• Ph.D., Physiology, (1996). Tulane University School of Medicine
• M.S., Physiology, (1994). Tulane University School of Medicine
• B.Sc. Honors, Biological Sciences (Physiology), (1989). University of Birmingham, UK.

 

COURSES TAUGHT

• Biology 4251/5251: Immunology
• Biology 6103/8103: Immunology of Infection

 

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

 

RESEARCH PROJECTS

1. The role of the neuropeptide substance P in microbe-induced inflammation

The tachykinin, 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.  Our laboratory has assembled a compelling body of evidence that substance P/NK-1R interactions exacerbate classical inflammation at mucosal sites and within the CNS.  We have demonstrated that macrophages and dendritic cells express NK-1R and showed that ligation of this receptor initiates the activation of the key inflammatory regulator NF-kB while inhibiting the production of the immunosuppressive cytokine TGF-b1.  Consistent with these effects on leukocytes, we demonstrated that substance P exacerbates the inflammatory responses of isolated brain glial cells, such as microglia and astrocytes, to clinically relevant bacterial pathogens including B. burgdorferi, N. meningitidis, and S. pneumoniae via NK-1R.  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.  The translational potential of these studies is underscored by our demonstration that prophylactic or therapeutic treatment of mice with a systemically delivered NK-1R antagonist attenuates the development of bacterially induced inflammatory CNS damage, and by our work showing that such antagonists can attenuate inflammatory responses in a non-human primate model of Lyme neuroborreliosis.  Recently, we have found that substance P can similarly exacerbate the inflammatory responses to resident bone cells to S. aureus, the principal causative agent of osteomyelitis.  As such, these data suggest that the NK-1R may represent an important new target in the treatment of microbe-induced inflammatory damage at sites as disparate as brain and bone tissue.

Current Project Support:

• NIH: 1R01 AI170012 “Substance P exacerbation of staphylococcal bone damage”
  

Recent Publications:

• Martinez, A.N., Burmeister, A.R., Ramesh, G., Doyle-Meyers, L., Marriott, I., and Philipp, M.T. (2017). Aprepitant limits in vivo neuroinflammatory responses in a rhesus model of Lyme neuroborreliosis. J. Neuroinflamm. 14: 37. PMID: 28202084
• Johnson, M.B., Young, A.D., and Marriott, I. (2017). The therapeutic potential of targeting substance P/NK-1R interactions in inflammatory CNS disorders. Front. Cell. Neurosci. 10: 296. PMID: 28101005
• Burmeister, A.R., Johnson, M.B., Chauhan, V.S., Moerdyk-Schauwecker, M., Young, A.D., Cooley, I.D., Martinez, A.N., Ramesh, G., Philipp, M.T., and Marriott, I. (2017). Human microglia and astrocytes constitutively express the neurokinin-1 receptor and functionally respond to substance P. J. Neuroinflamm. 14: 245. PMID: 29237453
• Johnson MB, Suptela SR, Sipprell SE, Marriott I. (2022). Substance P exacerbates the inflammatory and pro-osteoclastogenic responses of murine osteoclasts and osteoblasts to Staphylococcus aureus. Inflammation. In Press. PMID: 36040535.

2. Resident cells of the brain use cell surface and cytosolic pattern recognition receptors to recognize bacterial and viral pathogens.

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 the innate immune system recognizes a wide array of pathogens.  Studies from our group were among the first to demonstrate that glia express cell surface and endosomal TLRs that recognize bacterial and viral motifs.  In addition, we determined that glial cells also express cytosolic sensors for bacterial and viral motifs that may be more relevant for the detection of intracellular pathogens.  For example, we described the expression of NOD2 by glia and we demonstrated the essential role played by this molecule in inflammatory responses to clinically relevant bacterial CNS pathogens.  In addition, we discovered that glia express two members of the RLR family, RIG-I and MDA5, that function as cytosolic sensors for replicative RNA viruses.  We subsequently showed that RIG-I plays a critical role in the inflammatory responses of human astrocytes to neurotropic RNA viruses and, recently, showed that this sensor can also mediate the detection of bacterial nucleic acids in human microglia.  Finally, we described the expression of several cytosolic sensors for DNA in human and murine glia cells that include cyclic GMP-AMP synthase (cGAS), gamma-interferon inducible protein-16 (IFI16) and DNA-dependent activator of interferon-regulatory factors (DAI). Further, we have shown that cGAS mediates, in part, human microglial responses to exogenous cytosolic DNA, while DAI expression is critical for maximal inflammatory mouse glial responses to HSV-1 infection, suggesting that these novel cytosolic dsDNA sensors might play a critical role in the detection of replicative DNA viruses by glia.

Current Project Support:

• North Carolina Biotechnology Center: Flash Grant “Nucleic acid nanoparticles in the treatment of bacterial meningitis”

Recent Publications:

• Johnson, M.B., Halman, J.R., Burmeister, A.R., Currin, S., Khisamutdinov, E.F., Afonin, K.A., and Marriott, I. (2020).  Retinoic acid inducible gene-I mediated detection of bacterial nucleic acids in human microglial cells.  Neuroinflamm.  17: 139. PMID: 32357908.
• Jeffries, A.M., and Marriott, I. (2020). Cytosolic DNA sensors and CNS responses to viral pathogens.  Cell. Infect. Microbiol. 10: 501. PMID: 33042875
• Jeffries, A., Nikita, Truman, A.W., and Marriott, I. (2020).  The intracellular DNA sensors cGAS and IFI16 do not mediate effective immune responses to HSV-1 in human microglial cells.  Neurovirol. 26: 544-555.  PMID 32488842.
• Jeffries AM, Suptela AJ, Marriott I. (2022).  Z-DNA binding protein 1 mediates necroptotic and apoptotic cell death pathways in murine astrocytes following herpes simplex virus-1 infection. J Neuroinflammation. 19:109. PMID: 35549723.

3. The role of bone-forming osteoblasts in bacterially-induced inflammatory bone diseases

Osteomyelitis (OM) is a severe infection of bone tissue that is associated with significant morbidity and often leads to bone resorption, dysfunction, and progressive inflammatory destruction.  The Gram-positive organism, Staphylococcus aureus, is the most common causative agent of OM.  Despite improvements in prophylaxis and diagnosis this condition is often refractory to current treatment strategies and is recurrent.  An explanation for these phenomena may lie in the ability of the causative agents of OM to invade and persist within resident bone cells including osteoblasts (OB).  Importantly, our laboratory has demonstrated that isolated OBs utilize members of the TLR and NLR families of innate immune receptors to detect the presence of microbial products.  The activation of these sensors precipitates the production of inflammatory cytokines and chemokines, and antigen presenting and co-stimulatory molecules.  Consistent with this observation, our in vitro and in vivo studies show that S. aureus provides a potent stimulus for the production of soluble and cell surface molecules by isolated OBs that could play key roles in the initiation and/or progression of inflammatory immune responses, and enhance the activity of bone-resorbing osteoclasts. As such, the production of these mediators by bacterially challenged OBs may significantly contribute to involucrum and sequestrum formation during OM, and the development of damaging inflammatory host responses following infection.

Current Project Support:

• NIH: 1R01 AI170012 “Substance P exacerbation of staphylococcal bone damage”

Recent Publications:

• Becker, S.C., Roach, D.R., Chauhan, V.S., Shen, Y., Foster-Frey, J., Powell, A.M., Bauchan, G., Lease, R.A., Mohammad, H., Harty, W.J., Simmons, C., Schmelcher, M., Camp, M., Dong, S., Baker, J.R., Sheen, T.R., Doran, K.S., Pritchard, D.G., Almeida, R.A., Nelson, D.C., Marriott, I., Lee, J.C., and Donovan, D.M. (2016). Triple-acting Lytic Enzyme Treatment of Drug-Resistant and Intracellular Staphylococcus aureus.  Rep.  6: 25063. PMID: 27121552
• El-Ghannam, A., Greenier, M., Johnson, M., and Marriott, I. (2020).  Synthesis and characterization of porous bioactive SiC tissue engineering scaffold.  Biomed. Mater. Res. A.  108: 2162-2174.  PMID: 32319213.

4. Glial cells produce novel IL-10 family members and are sensitive to their immune regulatory effects

It is well known that glial cells contribute to neuroinflammation, but it is only now becoming apparent that glia also play an important role in producing and responding to immunosuppressive factors that serve to limit the detrimental effects of such responses.  IL-10 is generally considered to be the quintessential immunosuppressive cytokine and evidence has accumulated that CNS cells can produce and respond to this suppressive factor.  Recently, we have described the ability of microglia and astrocytes to express other members of the IL-10 cytokine family including IL-19, IL-20, and IL-24.  We have found that IL-19 and IL-24, like IL-10, are produced by glia in a delayed manner and these cytokines limit glial inflammatory responses.  In contrast, IL-20 is produced rapidly by glia and appears to act as a novel proinflammatory factor.

Recent Publications:

• Burmeister, A.R., and Marriott, I. (2018).  The interleukin-10 family of cytokines and their role in the CNS.  Cell. Neurosci. 12: 458. PMID: 30542269
• Burmeister, A.R., Johnson, M.B., and Marriott, I. (2019).  Murine astrocytes are responsive to the pro-inflammatory effects of IL-20.  Neurosci Lett.  708: 134334. PMID: 31238130.
• Burmeister, A.R., Johnson, M.B., Yaemongkol, J.J., and Marriott, I. (2019).  Murine astrocytes produce IL-24 and are susceptible to the immunosuppressive effects of this cytokine. J. Neuroinflamm. 16: 55. PMID: 30825881

CURRENT LAB MEMBERS

Alexander Suptela, Ph.D. Candidate

Sophie Sipprell, doctoral student

Andrew Dunphy, doctoral student