Positions

Overview

  • Dr. Raman’s laboratory interrogates molecular and cellular mechanisms driving the immunopathogenesis of autoimmune diseases with a special emphasis on multiple sclerosis (MS) and rheumatoid arthritis (RA). Within this are of research, the current studies focus on molecular mechanisms underlying activation and differentiation of effector T cells, B cells and innate cells in the pathogenesis of these autoimmune diseases. Current investigations involve human immunology bridged with mouse models to study RA and MS. The major area of investigation is immunopathogenesis of multiple sclerosis. We have several interrelated projects in this area of investigation:

    i. Type 1 IFNs (IFN-α and IFN-β) and type 2 IFN (IFN-γ) in pathogenesis and regulation of MS and RA – Our studies primarily focuses on outcomes of signaling from the IFN receptors in different innate and adaptive immune cell populations. Our immunopathogenic mechanism driving progression of multiple sclerosis (MS) that involves human studies and the mouse model, experimental autoimmune encephalomyelitis (EAE).

    ii. Molecular mechanisms by which CK2 and GSK3 modulates effector and regulatory cells in the pathogenesis of autoimmunity.

    iii. Role of CD5 in T cell and B-1a B cell development, differentiation, immunity and pathogenesis – the laboratory focuses on B-1a B cell-dependent T-independent antibody responses, T-dependent antibody responses, autoreactive B-cell generation and persistence and regulatory B-cells. For these studies, the Raman laboratory has generated unique knock-in CD5 mutant mice in which signaling domains associated with CD5-inhibitory activity (ITIM) and CD5-CK2 activation have been ablated.

    iv. TGFβR3/betaglycan dependent regulation of adaptive immune effector cells in the pathogenesis of autoimmune diseases
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 CD5 on dendritic cells regulates CD4+ and CD8+ T cell activation and induction of immune responses 2019
    2017 TβRIII is induced by TCR signaling and downregulated in FoxP3+ regulatory T cells 2017
    2016 CD5-CK2 signaling modulates ERK activation and thymocyte survival 2016
    2016 A Potential Structural Switch for Regulating DNA-Binding by TEAD Transcription Factors 2016
    2016 Apigenin, a Natural Flavonoid, Attenuates EAE Severity Through the Modulation of Dendritic Cell and Other Immune Cell Functions 2016
    2015 Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival 2015
    2015 Brief report: Expression of interferon-γ receptor genes in peripheral blood mononuclear cells is associated with rheumatoid arthritis and its radiographic severity in african americans 2015
    2015 Inhibition of system Xc<sup>-</sup> transporter attenuates autoimmune inflammatory demyelination 2015
    2015 MAT2A mutations predispose individuals to thoracic aortic aneurysms 2015
    2014 Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses 2014
    2014 CD5 enhances Th17-cell differentiation by regulating IFN-γ response and RORγt localization 2014
    2014 Therapeutic efficacy of suppressing the JAK/STAT pathway in multiple models of experimental autoimmune encephalomyelitis 2014
    2013 The interdependent, overlapping, and differential roles of type i and II IFNs in the pathogenesis of experimental autoimmune encephalomyelitis 2013
    2013 MHCII is required for α-Synuclein-induced activation of microglia, CD4 T cell proliferation, and dopaminergic neurodegeneration 2013
    2013 The carboxy-terminal region of CD5 is required for c-CBL mediated TCR signaling downmodulation in thymocytes 2013
    2013 Type i interferons: Beneficial in Th1 and detrimental in Th17 autoimmunity 2013
    2012 Lithium Controls Central Nervous System Autoimmunity through Modulation of IFN-γ Signaling 2012
    2012 Picosecond to second dynamics reveals a structural transition in clostridium botulinum no-sensor triggered by the activator BAY-41-2272 2012
    2012 CD5-dependent CK2 activation pathway regulates threshold for T Cell anergy 2012
    2012 Betaglycan (TβRIII) Is Expressed in the Thymus and Regulates T Cell Development by Protecting Thymocytes from Apoptosis 2012
    2012 Janus-like effects of type I interferon in autoimmune diseases 2012
    2012 Signal transducer and activator of transcription-3/suppressor of cytokine signaling-3 (STAT3/SOCS3) axis in myeloid cells regulates neuroinflammation 2012
    2012 Serine phosphorylation of FcγRI cytoplasmic domain directs lipid raft localization and interaction with protein 4.1G 2012
    2011 Green tea: A new option for the prevention or control of osteoarthritis 2011
    2011 Rescue of tumor-infiltrating lymphocytes from activation-induced cell death enhances the antitumor CTL response in CD5-deficient mice 2011
    2011 Pro-B cells sense productive immunoglobulin heavy chain rearrangement irrespective of polypeptide production 2011
    2011 Interferon-β exacerbates Th17-mediated inflammatory disease 2011
    2011 The immunomodulatory properties of the CD5 lymphocyte receptor in health and disease 2011
    2011 The reaction mechanism of allene oxide synthase: Interplay of theoretical QM/MM calculations and experimental investigations 2011
    2010 Increased antigen responsiveness of naive CD8 T cells exposed to IL-7 and IL-21 is associated with decreased CD5 expression 2010
    2010 T helper type 1 and 17 cells determine efficacy of interferon-Β in multiple sclerosis and experimental encephalomyelitis 2010
    2010 Marginal zone precursor B cells as cellular agents for type I IFN-promoted antigen transport in autoimmunity 2010
    2009 The structures of indazolin-3-one (=1,2-dihydro-3H-indazol-3-one) and 7-nitroindazolin-3-one 2009
    2009 Increased numbers of thymic and peripheral CD4+ CD25 +Foxp3+ cells in the absence of CD5 signaling 2009
    2009 Mutations in Smooth Muscle Alpha-Actin (ACTA2) Cause Coronary Artery Disease, Stroke, and Moyamoya Disease, Along with Thoracic Aortic Disease 2009
    2008 Structural insights into the evolutionary paths of oxylipin biosynthetic enzymes 2008
    2008 CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells 2008
    2008 Corrigendum: Mutations in smooth muscle α-actin (ACTA2) lead to thoracic aortic aneurysms and dissections (Nature Genetics (2007) 39, (1488-1493)) 2008
    2008 Erratum: MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor1 and angiotensin II (Human Molecular Genetics (2007) vol. 16 (20) (2453-2462) 10.1093/hmg/ddm201) 2008
    2008 Lithium prevents and ameliorates experimental autoimmune encephalomyelitis 2008
    2007 Mutations in smooth muscle α-actin (ACTA2) lead to thoracic aortic aneurysms and dissections 2007
    2007 MYH11 mutations result in a distinct vascular pathology driven by insulin-like growth factor 1 and angiotensin II 2007
    2007 Efficient synthesis of 7-substituted or 3,7-disubstituted 1H-indazoles 2007
    2007 A new mutation within the porphobilinogen deaminase gene leading to a truncated protein as a cause of acute intermittent porphyria in an extended indian family 2007
    2006 CD5-CK2 binding/activation-deficient mice are resistant to experimental autoimmune encephalomyelitis: Protection is associated with diminished populations of IL-17-expressing T cells in the central nervous system 2006
    2006 Analogies and surprising differences between recombinant nitric oxide synthase-like proteins from Staphylococcus aureus and Bacillus anthracis in their interactions with l-arginine analogs and iron ligands 2006
    2006 De novo mutation found in the porphobilinogen deaminase gene in Slovak acute intermittent porphyria patient: Molecular biochemical study 2006
    2006 Dynamics of NO rebinding to the heme domain of NO synthase-like proteins from bacterial pathogens 2006
    2005 Requirement of the Fc receptor common γ-chain for γδ T cell-mediated promotion of murine experimental autoimmune encephalomyelitis 2005
    2005 Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis 2005
    2005 Structural basis of hereditary coproporphyria 2005
    2005 Mutations in transforming growth factor-β receptor type II cause familial thoracic aortic aneurysms and dissections 2005
    2004 Femtomolar sensitivity of a NO sensor from Clostridium botulinum 2004
    2004 Cutting edge: Critical role for CD5 in experimental autoimmune encephalomyelitis: Inhibition of engagement reverses disease in mice 2004
    2004 A Redox-controlled Molecular Switch Revealed by the Crystal Structure of a Bacterial Heme PAS Sensor 2004
    2004 Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Faslpr mice from autoimmune disease 2004
    2003 The B cell coreceptor CD22 associates with AP50, a clathrin-coated pit adapter protein, via tyrosine-dependent interaction 2003
    2002 CD5, an important regulator of lymphocyte selection and immune tolerance 2002
    2002 AP2 adaptor complex-dependent internalization of CD5: Differential regulation in T and B cells 2002
    2001 Structural basis for pterin antagonism in nitric-oxide synthase: Development of novel 4-oxo-pteridine antagonists of (6R)-5,6,7,8-tetrahydrobiopterin 2001
    2001 Crystal structure of nitric oxide synthase bound to nitro indazole reveals a novel inactivation mechanism 2001
    2001 Implications for Isoform-selective Inhibitor Design Derived from the Binding Mode of Bulky Isothioureas to the Heme Domain of Endothelial Nitric-oxide Synthase 2001
    2001 CD45 function is regulated by an acidic 19-amino acid insert in domain II that serves as a binding and phosphoacceptor site for casein kinase 2 2001
    2001 Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based inhibitors 2001
    2000 Mapping the active site polarity in structures of endothelial nitric oxide synthase heme domain complexed with isothioureas 2000
    2000 Antibody-detected folding: Kinetics of surface epitope formation are distinct from other folding phases 2000
    1999 Factors determining the selectivity of protein tyrosine nitration 1999
    1999 Crystal structures of zinc-free and -bound heme domain of human inducible nitric-oxide synthase. Implications for dimer stability and comparison with endothelial nitric-oxide synthase 1999
    1999 Zinc content of Escherichia coli-expressed constitutive isoforms of nitric-oxide synthase. Enzymatic activity and effect of pterin 1999
    1999 Heme-mediated oxygen activation in biology: Cytochrome c oxidase and nitric oxide synthase 1999
    1999 Isothermal titration calorimetry of protein-protein interactions 1999
    1998 The C331A mutant of neuronal nitric-oxide synthase is defective in arginine binding 1998
    1998 Crystal structure of constitutive endothelial nitric oxide synthase: A paradigm for pterin function involving a novel metal center 1998
    1998 Cutting edge: Differential CD5-dependent regulation of CD5-associated CK2 activity in mature and immature T cells: Implication on TCR/CD3-mediated activation 1998
    1998 Differential CD5-dependent regulation of CD5-associated CK2 activity in mature and immature T cells: implication on TCR/CD3-mediated activation. 1998
    1998 Regulation of casein kinase 2 by direct interaction with cell surface receptor CD5 1998
    1998 CD5 regulates Casein Kinase 2 (CK2) by direct interaction with the holoenzyme 1998
    1998 Interaction of AP50 with the cytoplasmic domain of murine CD22.2 1998
    1998 NO news is good news 1998
    1997 CYS 331 of neuronal nitric oxide synthase is involved in L-arg binding rather than direct BH4 binding 1997
    1997 Human Ig heavy chain CDR3 regions in adult bone marrow pre-B cells display an adult phenotype of diversity: Evidence for structural selection of D(H) amino acid sequences 1997
    1997 Cloning and characterization of HUPF1, a human homolog of the Saccharomyces cerevisiae nonsense mRNA-reducing UPF1 protein 1997
    1997 Human coproporphyrinogen oxidase. Biochemical characterization of recombinant normal and R231W mutated enzymes expressed in E. coli as soluble, catalytically active homodimers. 1997
    1997 Molecular mechanisms governing reading frame choice of immunoglobulin diversity genes 1997
    1995 Sequence of the rabbit glyceraldehyde-3-phosphate dehydrogenase-encoding cDNA 1995
    1995 Enthalpy of Antibody—Cytochrome c Binding 1995
    1995 High hydrostatic pressure induces the dissociation of cpn60 tetradecamers and reveals a plasticity of the monomers 1995
    1994 MPSA short communications 1994
    1994 Preferential VH gene usage in rabbit Ig-secreting heterohybridomas 1994
    1992 CD5+ B cells predominate in peripheral tissues of rabbit 1992
    1992 Diffusion-Limited Rates for Monoclonal Antibody Binding to Cytochrome c 1992
    1992 Identification and Cloning of Rabbit CD5 1992
    1990 Evaluation of an elsa for the detection of anti‐histoplasma ribosomal and antihistoplasmin antibodies in histoplasmosis 1990

    Book

    Year Title Altmetric
    2000 Structures of gas-generating heme enzymes: Nitric oxide synthase and heme oxygenase.  Ed. 51.  2000

    Full Name

  • Chander Raman