Autoimmune Diseases of the Nervous System
Paraneoplastic Syndromes, Nervous System
Health Informatics And Implementation Science
<p >Potential rotation projects My lab primarily investigates Plasmodium falciparum malaria-induced dysregulation of EBV-specific T cell immunity and its role in the etiology of endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in Equatorial Africa. Within the context of our ongoing studies of healthy Kenyan children with divergent malaria exposure histories (chronic/repeated infections in a holoendemic area versus low infection rates in a nearby highland, malaria hypoendemic area) and by examining children diagnosed with eBL we have established a repository of samples that can be used to address this question. <p >1. One avenue of exploration involves homeostatic cytokine regulation of memory T cells. IL-15 and/or IL-7 responsiveness of EBV-specific memory T cells may be impaired in children with chronic malaria exposure and in children with endemic Burkitt lymphoma (eBL). We would like to investigate IL-15Ra and IL-7Ra surface expression, and CFSE proliferation of EBV-specific T cells in response to cognate antigen with and without IL-15 or IL-7 stimulation and compared children with divergent malaria exposure histories and children diagnosed with eBL. T cell responsiveness to IL-15 and IL-7 can be measured by STAT5 phosphorylation and the specificity of this effect for EBV-specific T cells can be evaluated by comparing IL-15Ra and IL-7Ra expression and responsiveness on other lymphocyte subsets and CMV-specific T cells. <p >2. Another putative mechanism by which malaria may interfere with the development of immunologic memory and influence EBV-specific T cell immunity is through the Programmed death-1 (PD-1) pathway. PD-1 is an immune inhibitory molecule that negatively regulates activated immune cells upon interacting with its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2) resulting in down-regulation of immune responses. Previous studies in murine and primate viral and parasitic diseases have reported the up-regulation of PD-1 and soluble PD-1 (sPD-1) but no studies have reported the expression of PD-1 in individuals from areas with divergent malaria transmission dynamics or in children presenting with endemic Burkitt lymphoma (eBL). In addition the PD-1 pathway has been suggested to be involved in the evasion of antitumor immunity by the host immune system. Preliminary studies in my lab suggest that PD-1 expression is significantly increased on CD4, CD8 T cells, B cells and NK cells in those residing in high malaria transmission areas compared to age-matched individuals without a history of malaria exposure. Future studies will explore the kinetics of this effect, the impact of antigen dose and how malaria exploits PD-1 mediated regulation to impair the development of immunologic memory. <p >3. Another area of interest is the role of Th17 cells in pediatric immunity. Because of the naturally delayed production of TH1 mediated pro-inflammatory cytokines (i.e. IL-12 and IFN-g) in utero, neonatal immunity is thought to be Ã¢â‚¬ËœsuppressedÃ¢â‚¬â„¢. However, more recent studies have shown that neonatal monocytes and antigen-presenting cells do express pro-inflammatory and regulatory cytokines (i.e. IL-6, IL-10 and IL-23) and at higher levels than adults. Thus TH17 cells appear to be an early, sequential response to pathogens prior to the induction of a TH1 or TH2 response. TH17 cells are also stimulated with IL-21 and IL-22 in an autocrine and paracrine fashion by natural killer cells. Exploring Th17 cell responses within the context of early-age human infections with malaria and EBV would be an exciting new avenue of investigation in my laboratory.
Raibagkar P, Berkowitz AL. The Many Faces of Neurocysticercosis. J Neurol Sci. 2018 07 15; 390:75-76.
Raibagkar P, Chavali RV, Kaplan TB, Kim JA, Nitka MV, Chou SH, Edlow BL
Raibagkar P, Chavali RV, Kaplan TB, Kim JA, Nitka MV, Chou SH, Edlow BL. Reverse Locked-In Syndrome. Neurocrit Care. 2017 Aug; 27(1):108-114.
Neagu MR, Raibagkar P, Lyons JL, Klein JP
Neagu MR, Raibagkar P, Lyons JL, Klein JP. Imaging in Neurologic Infections II: Fungal and Viral Diseases. Curr Infect Dis Rep. 2015 Apr; 17(4):474.
Imaging in Neurologic Infections II: Fungal and Viral Diseases.
Raibagkar P, Ferry JA, Stone JH. Is MuSK myasthenia gravis linked to IgG4-related disease? J Neuroimmunol. 2017 04 15; 305:82-83.
Is MuSK myasthenia gravis linked to IgG4-related disease?
Cai X, Bhattacharyya S, Plitt A, Raibagkar P, LaBuzetta JN, Schleicher SM, Munshi NC, Klein JP
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Cai X, Bhattacharyya S, Plitt A, Raibagkar P, LaBuzetta JN, Schleicher SM, Munshi NC, Klein JP. Management of Posterior Reversible Encephalopathy Syndrome Induced by Carfilzomib in a Patient With Multiple Myeloma. J Clin Oncol. 2016 Jan 10; 34(2):e1-5.
Management of Posterior Reversible Encephalopathy Syndrome Induced by Carfilzomib in a Patient With Multiple Myeloma.
Raibagkar P, Neagu MR, Lyons JL, Klein JP
Raibagkar P, Neagu MR, Lyons JL, Klein JP. Imaging in neurologic infections I: bacterial and parasitic diseases. Curr Infect Dis Rep. 2014 Dec; 16(12):443.
Imaging in neurologic infections I: bacterial and parasitic diseases.
Money KM, Mahatoo A, Samaan S, Anand P, Baber U, Bailey M, Bakshi R, Bouley A, Bower A, Cahill J, Houtchens M, Katz J, Lathi E, Levit E, Longbrake EE, McAdams M, Napoli S, Raibagkar P, Wade P, Sloane JA
Neurology(R) neuroimmunology & neuroinflammation
Money KM, Mahatoo A, Samaan S, Anand P, Baber U, Bailey M, Bakshi R, Bouley A, Bower A, Cahill J, Houtchens M, Katz J, Lathi E, Levit E, Longbrake EE, McAdams M, Napoli S, Raibagkar P, Wade P, Sloane JA. A New England COVID-19 Registry of Patients With CNS Demyelinating Disease: A Pilot Analysis. Neurol Neuroimmunol Neuroinflamm. 2021 09; 8(5).
A New England COVID-19 Registry of Patients With CNS Demyelinating Disease: A Pilot Analysis.
Bhattacharyya S, Darby RR, Raibagkar P, Gonzalez Castro LN, Berkowitz AL
Bhattacharyya S, Darby RR, Raibagkar P, Gonzalez Castro LN, Berkowitz AL. Antibiotic-associated encephalopathy. Neurology. 2016 Mar 08; 86(10):963-71.
Raibagkar P. Immune checkpoint inhibitor associated neurotoxicity: Much more than meets the eye. Immunol Lett. 2020 05; 221:72-74.
Immune checkpoint inhibitor associated neurotoxicity: Much more than meets the eye.
Berkowitz AL, Raibagkar P, Pritt BS, Mateen FJ
Berkowitz AL, Raibagkar P, Pritt BS, Mateen FJ. Neurologic manifestations of the neglected tropical diseases. J Neurol Sci. 2015 Feb 15; 349(1-2):20-32.
Neurologic manifestations of the neglected tropical diseases.
Population and Quantitative Health Sciences
Jayashri Srinivasan MD, PhD, FRCP, FAAN, FANA
Ridha M, Jones DG, Lerner DP, Vytopil M, Voetsch B, Burns JD, Ramineni A, Raibagkar P
Ridha M, Jones DG, Lerner DP, Vytopil M, Voetsch B, Burns JD, Ramineni A, Raibagkar P. The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation. Virol J. 2021 08 06; 18(1):162.
The spectrum of Epstein-Barr virus infections of the central nervous system after organ transplantation.
Raibagkar P, Ho D, Gunturu KS, Srinivasan J
Raibagkar P, Ho D, Gunturu KS, Srinivasan J. Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature. J Neuroimmunol. 2020 04 15; 341:577184.
Worsening of anti-Hu paraneoplastic neurological syndrome related to anti-PD-1 treatment: Case report and review of literature.
Joseph D. Early Chair in Biomedical Research
Raibagkar P, Ramineni A. Autoimmune Neurologic Emergencies. Neurol Clin. 2021 05; 39(2):589-614.