The Koralnik laboratory is involved in the study of the immunopathogenesis of JC virus (JCV), the agent of Progressive Multifocal Leukoencephalopathy (PML), and the development of an animal model for this disease which affects immunosuppressed individuals with AIDS, leukemias, and organ transplant recipients. We are also studying the virologic and metabolic determinants of PML, and developping immunotherapies for this disease. Furthermore, we have identified a JC virus variant which infects and destroys granule cell neurons of the cerebellum, and characterized a novel disease entity called JCV granule cell neuronopathy (JCV GCN). In addition, we are studying the immune response against the polyomavirus BK (BKV), which causes a nephropathy in renal transplant recipients.
Du Pasquier, RA, Kuroda M, Zheng Y, Jean-Jacques J, Letvin NL, Koralnik IJ. A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of Progressive Multifocal Leukoencephalopathy. Brain 2004, 127(9):1970-1978
Lima MA, Marzocchetti A, Autissier P, Tompkins T, Chen Y, Gordon J, Clifford DB, Gandhi RT, Venna N, Berger JR, Koralnik IJ. Frequency and phenotype of JC virus-specific CD8 T lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy. J. Virology 2007, 81:3361-8
Wuethrich C, Cheng, YM, Joeseph JT, Kesari S, Beckwith C, Stopa E, Bell JE, Koralnik IJ. Frequent infection of cerebellar granule cell neurons by JC virus in patients with progressive multifocal leukoencephalopathy, J Neuropath Exp Neurol 2009 68:15-25. NIHMSID 87313
Tan CS, Dezube BJ, Bhargava P, Autissier P, Wuethrich C, Miller J, Koralnik IJ. Detection of JC virus DNA and proteins in bone marrow of HIV and HIV- patients: implications for viral latency and neurotropic transformation. J Infect Dis 2009, 1999:881-8, NIHMSID 90990
Chen Y, Bord E, Tompkins T, Miller J, Tan CS, Kinkel RP, Stein MC, Viscidi R, Ngo LH, Koralnik IJ. Asymptomatic reactivation of JC virus in multiple sclerosis patients treated with natalizumab. New Engl J Med 2009. 361:1067-74
External Recognition:
1990 John Bizot Prize for M.D. thesis, Geneva University Medical School
1991 Swiss Society of Internal Medicine Award
2001 Best Clinical Science Poster Award, Beth Israel Deaconess Medical Center Research Day (selected out of 158 presentations)
2003 Committee On Microbiological Safety, Harvard Medical School
2003 Reviewer, special emphasis panel/initial review group 2004/01 ZAI1 BLG-I (J1), Pathogenesis of Polyomavirus Associated Nephropathy, NIAID, NIH
2003 Panel member, Validation of a Causal Relationship: Criteria to Establish Etiology of Carcinogens, NCI, NIH
2005 Committee on Public Policy, American Neurological Association
2005 Harvard Center for AIDS Research (CFAR) feasibility and scholar awards review panel, Reviewer
2005 Selective Adhesion Molecules Inhibitors and CNS Disease, NINDS, Panel Member
2005 National NeuroAids Tissue Consortium (NNTC) scientific agenda meeting: Future directions, NIMH, Panel Member
2006 Board of Scientific Counselors, Basic Neurosciences Program, NINDS, site visit of Laboratory of Molecular Medicine and Neuroscience, Eugene O. Major,Chief, Reviewer
2006 SV40 assay development working group meeting, NCI, Panel Member
2006 Special Emphasis Panel/Scientific Review Group 2007/01 ZRG1 AARR-D, Reviewer
2008 Member, American Society for Clinical Investigation
Major Collaborative Activities:
Collaboration with Robert Lenkinski PhD, BIDMC, on Magnetic Resonance Spectroscopy studies of PML , and Rajesh Gandhi, MGH, on dendritic cell based immunotherapy of PML. Collaboration with Bruce Dezube and Parul Barghawa, BIDMC on detection of JCV in bone marrow samples. Collaboration with Rip Kinkel, BIDMC, on JCV studies in MS patients treated with natalizumab.
