Holtom-Garrett Professor of Neurology
Director, U-M Multiple Sclerosis Center
Our research investigates how chemokine and cytokine networks and leukocyte subsets act together, both in peripheral lymphoid tissues and the central nervous system (CNS), to mediate autoimmune diseases that target neuronal or glial antigens normally sequestered behind the blood-brain-barrier . We are particularly interested in the inflammatory demyelinating disease, multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). One part of the laboratory is devoted to human immunological studies (involving the analysis of peripheral blood and cerebrospinal fluid mononuclear cells that are collected from patients with MS or other neurological diseases and healthy controls). Currently we are investigating the relationship between the expression of selected cytokines (such as IL-23 and IL-17) and disease activity, as detected by advanced MRI techniques, in individuals with progressive multiple sclerosis. A complementary division of our lab is dedicated to animal studies, primarily using the EAE model.
Some of our on-going projects are to investigate the following: (i) the expression pattern and role of the interleukin (IL)-12 p40 family of monokines in secondary progressive MS; (ii) the role of IL-12 and IL-23 in T cell homing to the CNS and epitope spreading during the course of EAE; (iii) CNS expression and functional significance of “lymphoid” chemokines, such as CXCL13 and CCL21, in driving the formation of organized inflammatory infiltrates during relapsing EAE and MS; (iv) the origin and biological activities of dendritic cells that accumulate in demyelinating lesions during EAE; (v) the importance of regulatory T cells for remission during relapsing autoimmune demyelination; (vi) the role of neutrophils and the chemokines that attract them in blood-brain-barrier breakdown during EAE; and (vii) the impact of b -IFN therapy on the immune system of patients with MS.
Becher B and Segal BM. Th17 cells in CNS Autoimmunity. Current Opinions in Immunology. 2011; 23(6):707-12. PMCID: PMC3535446
Tian W, Zhu T, Zhong J, Liu X, Rao P, Segal BM, Ekholm S. Progressive Decline in Fractional Anisotropy on Serial DTI Examinations of the Corpus Callosum: A Putative Marker of Disease Activity and Progression in SPMS. Neuroradiology 2012; 54(4):287-97
Braley TJ, Segal BM and Chervin RD. Sleep-disordered breathing in multiple sclerosis. Neurology 2012; 79(9):929-36. PMCID: PMC3425840
Braley TJ, Young HL, Mohan S, Segal BM, Berini S and Srinivasan A. Differences in diffusion tensor imaging derived metrics in the corpus callosum of multiple sclerosis patients without and with gadolinium enhancing cerebral lesions. Journal of Computer Assisted Tomography 2012; 36: 410-415.
Segal BM. The unwavering commitment of regulatory T cells in the suppression of autoimmune encephalomyelitis: Another aspect of immune privilege in the CNS. Eur J Immunol 2012; 42(5):1102-5.
Rao, P and Segal BM. Experimental autoimmune encephalomyelitis. Methods Mol Biol. 2012; 900:363-80.
Braley TJ, Chervin RD and Segal BM. Fatigue, tiredness, lack of energy, and sleepiness in multiple sclerosis patients referred for clinical polysomnography. Multiple Sclerosis International 2012; 2012:673936. PMCID: PMC3539354
Segal BM. Neurosarcoidosis-- Diagnostic Approaches and Therapeutic Strategies. Curr Opin Neurol. 2013; E pub ahead of print. PMC Journal – In Process
Braley T and Segal BM. B cell-targeting agents in the treatment of multiple sclerosis. Curr Treatment Options in Neurology. 2013; PMCID: PMC3677195
Beran RG, Braley TJ, Segal BM and Chervin RD. Sleep-disordered breathing in multiple sclerosis. Neurology 2013; 80: 1354-5. PMCID: PMC3425840
Lalor S and Segal BM. TH1 mediated experimental autoimmune encephalomyelitis in CXCR3-independent. Eur. J. Immunol.; In Press
Rainey-Barger EK, Blakely PK, Huber AK, Segal BM and Irani DN. Virus-induced CD8+ T cells accelerate the onset of experimental autoimmune encephalomyelitis: implications for how viral infections might trigger multiple sclerosis exacerbations. J Neuroimmunol. 2013; In Press. PMCID: PMC3654028
Sandy AR, Stoolman J, Mallot K, Pangtornpipat P, Segal BM and Maillard I. Notch signaling regulates T cell accumulation and function in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol 2013; 191(4):1606-1613. PMCID: PMC3735619.
Lalor SJ, Segal BM. Th1-mediated experimental autoimmune encephalomyelitis is CXCR3 independent. Eur J Immunol 2013; 43(11):2866-74. PMID: 23873018
Grifka-Walk HM, Lalor SJ, and Segal BM. Highly polarized Th17 cells induce EAE via a T-bet independent mechanism. Eur. J. Immunol 2013 Nov; 43(11):2824-2831. PMCID: PMC3838449.
Braley TJ, Segal BM, and Chervin RD. Obstructive sleep apnea and fatigue in patients with multiple sclerosis. J Clin Sleep Med 2014;10(2):155-162. PMCID: PMC3899317.
Segal BM. Stage Specific Immune Dysregulation in Multiple Sclerosis. Journal of Interferon & Cytokine Research 2014 (In Press).
Rumble J and Segal BM. In Vitro Polarization of Th cells. In “T-Helper Cells: Methods and Protocols” (A. Waisman and B. Becher, ed.s) 2014 (In Press).
Stoolman JS, Duncker PC, Huber AK and Segal BM. Site-specific chemokine expression regulates CNS inflammation and determines clinical phenotype in autoimmune encephalomyelitis. J Immunol 2014; PMCID: PMC409164.
Braley TJ, Segal BM, Chervin RD. Obstructive sleep apnea is an under-recognized and consequently morbidity in multiple sclerosis. J Clin Sleep Med 2014; 10(6):709-10. PMCID: PMC4031420