Marlene Kanmogne

MSTP in PhD Training

Program: Neurosciences

Current advisor: Robyn S. Klein, MD, PhD

Undergraduate university: Johns Hopkins University, 2016

Enrollment year: 2016

Research summary
Investigating Classical Complement Protein Signaling in Viral Neuroinflammatory Responses.

My projects aim to evaluate the mechanisms of complement ligand and complement receptor mediated acute neuroinflammation following West Nile virus Neuroinvasive Disease (WNND). West Nile virus (WNV) is the leading cause of domestically acquired arboviral disease in the United States and infection can lead to a severe neuroinvasive outcomes (i.e. meningitis, acute flaccid paralysis) termed WNND. Furthermore, patients who survive the acute neuroinvasive syndromes can experience long term memory deficits. Currently there are no treatments for the acute or latent cognitive deficits, but a role for complement proteins has been established. The Klein lab has shown that following WNV infection, microglia prune neuronal synapses in a complement dependent manner. I will expand on this by evaluating: 1) The CNS production of classical complement proteins post infection. 2) How C1q (initiating ligand) and C3aR (inflammatory receptor) impacts microglial cell activation post infection. 3) How C1q and C3aR impact spatial learning and memory and molecular neural correlates of learning such as synapse elimination post infection. 4) How C3aR impacts peripheral immune cell recruitment and activation post infection. And 5) Develop a role for complement protein C4 in WNND. I will be using a combination of neuroscience and immunology based techniques to evaluate these objectives including: flow cytometry, immunohistochemistry, qRT-PCR, and Barnes Maze behavioral testing. Furthermore, I will use Cre-Lox technology to specifically delete C1q from multiple cell types (i.e. microglia and neurons) to better study the cell specific role of complement proteins in WNND.

Graduate publications
Kanmogne M, Klein RS. 2021 Neuroprotective versus Neuroinflammatory Roles of Complement: From Development to Disease. Trends Neurosci, 44(2):97-109.

Garber C, Soung A, Vollmer LL, Kanmogne M, Last A, Brown J, Klein RS. 2019 T cells promote microglia-mediated synaptic elimination and cognitive dysfunction during recovery from neuropathogenic flaviviruses. Nat Neurosci, 22(8):1276-88.

Klein RS, Garber C, Funk KE, Salimi H, Soung A, Kanmogne M, Manivasagam S, Agner S, Cain M. 2019 Neuroinflammation During RNA Viral Infections. Annu Rev Immunol, 37():73-95.

Garber C, Soung A, Vollmer L, Kanmogne M, Last A, Brown J, Klein RS. (2017) Interferon gamma inhibits cognitive recovery from viral encephalitis. ISN Satellite meeting Immune Cells and the CNS, Chateau de Cely, France, Abstract.

Garber C, Soung A, Vollmer L, Kanmogne M, Last A, Brown J, Klein RS. (2017) T-Cell Activation of Microglia Prevents Complete Cognitive Recovery from WNV encephalitis. Gordon Research Seminar, Viruses and Cells, Lucca (Barga), Italy, Abstract.

Garber C, Soung A, Vollmer L, Kanmogne M, Last A, Brown J, Klein RS. (2017) Cytokine mediated decreases in adult neurogenesis underlie cognitive dysfunction following viral encephalitis. 2017 Hope Center Retreat, Creve Coeur, MO, Abstract.

Garber C, Soung A, Vollmer L, Kanmogne M, Last A, Brown J, Klein RS. (2017) Neuroimmune mechanisms inhibit cognitive recovery from viral encephalitis. ASCI/AAP/APSA Annual Joint Meeting, Chicago, IL, Abstract.