Ritu Chakravarti
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Associate Professor
BMSP Cellular Signaling Course Director
Assistant Professor, Physiology and Pharmacology , College of Medicine and Life Sciences
Contact Info
Overview
overview
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I am an investigator with demonstrated expertise and a passion for studying pathologies associated with autoimmune diseases such as arthritis and vasculitis. The current focus of the Chakravarti Laboratory is to research cytokine signaling in arthritis and its related pathologies. In particular, we study the role of 14-3-3z, an intracellular protein with well-known adaptor functions, in immune regulations. We first identified a new auto-antigenic property of 14-3-3z (Arthritis & Rheumatology-2015). My experience examining adaptor proteins (Proc Natl Acad Sci-2010, JBC-2012, FRBM-2015, Structure-2015, JBC-2018) enabled me to pose fundamental questions to understand how this protein operates in the context of an autoimmune disease. Some of the highlights of our contributions include the following- (1) characterizing how exogenous 14-3-3z can skew human T cell polarization ex vivo and identifying unique epitopes that contribute to its specificity (PLoS One-2017, Front Immunol-2019, J Mol Med-2020), (2) demonstrated that 14-3-3z is uniquely essential for IL-17 receptor signaling to induce IL6 but negatively regulates CXCL1. This unique regulation requires interactions of TRAF proteins with 14-3-3z, which has functional consequences on IL-17A signaling (Proc Natl Acad Sci-2020, Immunobiology-2021). This project is currently funded by NIH-R01. My laboratory developed a novel CRISPR-Cas9-edited deletion rat model of 14-3-3z and demonstrated that 14-3-3z is essential to curb the severity of arthritis and strongly prevent inflammation-associated bone loss (Proc Natl Acad Sci-2021). The project has resulted in one successful US patent application and attracted significant media attention from 60 news outlets, including BBC World News Radio. This attention underscores the importance of our work to millions suffering from inflammatory arthritis worldwide and, more importantly, ignites my curiosity to understand the mechanisms governing protection from bone loss and joint inflammation. We have received very encouraging feedback from the RA community worldwide, so we are determined to invest in it and bring it to clinical trials to relieve millions. To understand how 14-3-3z plays an immune suppressive role in arthritis, we examined its role in RANKL-mediated bone loss. We determined a novel mechanism of its action (Journal of Biological Chemistry, 2024). We are further investigating the human connection of 14-3-3z to pathologies during bioinformatics analyses (Genes, 2024).
My research has been funded by the National Institute of Health, Ohio Department of Health, American Heart Association, Vasculitis Foundation, and CSTR grants.
In addition to collaborative research, I have important education and service components. I have trained more than 15 post-graduate students, 10 medical students, and three technicians in lab research and management. At the college level, I serve as Course Director of ‘Basis of Cellular Signaling’ in the College of Graduate Studies (for the last five years) and the “Medical Student’s Summer Research” program. I have served as director of the 'Molecular Medicine' graduate track, coordinator of the 'Pre-Med Summer Camp' at the College of Medicine & Life Sciences, and coordinator of the 'Training Leaders Club' at the Department of Physiology & Pharmacology. I am heavily involved in teaching and advising students in the MD curriculum. I teach several topics related to cellular signaling and cardiovascular and pulmonary physiology to 1st and 2nd-year medical students. I also co-led learning pod sessions for 10-12 first-year MD students to educate them on various professional and scientific issues for three years. Currently, I am vice president of the COMLS Faculty Council. I also represent COMLS at the Faculty Council and IACUC committee at the institutional level.
Overall, I am a curious researcher and an engaging teacher.
Publications
selected publications
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Article (Web of Science)
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202014-3-3 zeta-TRAF5 axis governs interleukin-17A signaling. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 117:25008-25017.Full Text via DOI: 10.1073/pnas.2008214117 PMID: 32968020
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2020High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication. VIRUSES-BASEL. 12.Full Text via DOI: 10.3390/v12040442 PMID: 32295140
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2020The interferon-inducible protein TDRD7 inhibits AMP-activated protein kinase and thereby restricts autophagy-independent virus replication. JOURNAL OF BIOLOGICAL CHEMISTRY. 295:6811-6822.Full Text via DOI: 10.1074/jbc.ra120.013533
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201914-3-3 zeta-A Novel Immunogen Promotes Inflammatory Cytokine Production. FRONTIERS IN IMMUNOLOGY. 10.Full Text via DOI: 10.3389/fimmu.2019.01553 PMID: 31396202
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2018Glyceraldehyde-3-phosphate dehydrogenase is a chaperone that allocates labile heme in cells. JOURNAL OF BIOLOGICAL CHEMISTRY. 293:14557-14568.Full Text via DOI: 10.1074/jbc.RA118.004169
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2018Nitric oxide alters hyaluronan deposition by airway smooth muscle cells. PLOS ONE. 13.Full Text via DOI: 10.1371/journal.pone.0200074
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2018Glyceraldehyde-3-phosphate dehydrogenase is a chaperone that allocates labile heme in cells. JOURNAL OF BIOLOGICAL CHEMISTRY. 293:14557-14568.Full Text via DOI: 10.1074/jbc.ra118.004169
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2017Bioinformatic analysis reveals new determinants of antigenic 14-3-3 proteins and a novel antifungal strategy. PLOS ONE. 12.Full Text via DOI: 10.1371/journal.pone.0189503
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2017Qualitative and Quantitative Assay for Detection of Circulating Autoantibodies against Human Aortic Antigen. BIO-PROTOCOL. 7.Full Text via DOI: 10.21769/bioprotoc.2367
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201514-3-3 in Thoracic Aortic Aneurysms: Identification of a Novel Autoantigen in Large Vessel Vasculitis. ARTHRITIS & RHEUMATOLOGY. 67:1913-1921.Full Text via DOI: 10.1002/art.39130
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2015A Bipartite Interaction between Hsp70 and CHIP Regulates Ubiquitination of Chaperoned Client Proteins. STRUCTURE. 23:472-482.Full Text via DOI: 10.1016/j.str.2015.01.003
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2015Novel insights in mammalian catalase heme maturation: Effect of NO and thioredoxin-1. FREE RADICAL BIOLOGY AND MEDICINE. 82:105-113.Full Text via DOI: 10.1016/j.freeradbiomed.2015.01.030
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2014Hydrogen sulfide and nitric oxide metabolites in the blood of free-ranging brown bears and their potential roles in hibernation. FREE RADICAL BIOLOGY AND MEDICINE. 73:349-357.Full Text via DOI: 10.1016/j.freeradbiomed.2014.05.025
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2012Abnormal platelet aggregation in idiopathic pulmonary arterial hypertension: role of nitric oxide. AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY. 302:L512-L520.Full Text via DOI: 10.1152/ajplung.00289.2011
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2012Heme Binding Properties of Glyceraldehyde-3-phosphate Dehydrogenase. BIOCHEMISTRY. 51:8514-8529.Full Text via DOI: 10.1021/bi300863a
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2012Thioredoxin-1 Regulates Cellular Heme Insertion by Controlling S-Nitrosation of Glyceraldehyde-3-phosphate Dehydrogenase. JOURNAL OF BIOLOGICAL CHEMISTRY. 287:16179-16186.Full Text via DOI: 10.1074/jbc.m112.342758
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2010GAPDH regulates cellular heme insertion into inducible nitric oxide synthase. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 107:18004-18009.Full Text via DOI: 10.1073/pnas.1008133107
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2010Nitric oxide blocks cellular heme insertion into a broad range of heme proteins. FREE RADICAL BIOLOGY AND MEDICINE. 48:1548-1558.Full Text via DOI: 10.1016/j.freeradbiomed.2010.02.038
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2008Novel role of the muskelin–RanBP9 complex as a nucleocytoplasmic mediator of cell morphology regulation. JOURNAL OF CELL BIOLOGY. 182:727-739.Full Text via DOI: 10.1083/jcb.200801133
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2005Functional Role of Syndecan-1 Cytoplasmic V Region in Lamellipodial Spreading, Actin Bundling, and Cell Migration. MOLECULAR BIOLOGY OF THE CELL. 16:3678-3691.Full Text via DOI: 10.1091/mbc.e04-10-0907
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2002Optimization of compactin production in chemically defined production medium by Penicillium citrinum using statistical methods. Process Biochemistry. 38:481-486.Full Text via DOI: 10.1016/s0032-9592(02)00138-3
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Editorial Material (Web of Science)
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2018Ifi204/p204, a new piece in the sepsis puzzle. ANNALS OF TRANSLATIONAL MEDICINE.Full Text via DOI: 10.21037/atm.2018.09.22
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Meeting Abstract (Web of Science)
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2018INHIBITION OF 14-3-3 PROTEINS PROVIDES A NOVEL ANTIFUNGAL STRATEGY. JOURNAL OF INVESTIGATIVE MEDICINE. 830-830.Full Text via DOI: 10.1136/jim-2018-000745.89
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201714-3-3: AN ADHESIVE PROTEIN OF MEDIAL INFLAMMATION. JOURNAL OF INVESTIGATIVE MEDICINE. 874-874.Full Text via DOI: 10.1136/jim-2017-000448.144
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2015Treatment With Sodium Nitrite Improves the Pulmonary Function of Rejected Human Lungs in Cellular Ex Vivo Lung Perfusion Model. The Journal of Heart and Lung Transplantation. S139.Full Text via DOI: 10.1016/j.healun.2015.01.374
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2014NO and denitrosylases regulate maturation of active catalase by influencing its heme incorporation and tetrameric structure. NITRIC OXIDE-BIOLOGY AND CHEMISTRY. 117.Full Text via DOI: 10.1016/j.niox.2014.09.057
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2014Nitric oxide alters hyaluronan deposition by cultured airway smooth muscle cells and correlates with hyaluronan levels in asthmatics. NITRIC OXIDE-BIOLOGY AND CHEMISTRY. 99.Full Text via DOI: 10.1016/j.niox.2014.09.007
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2014Pre-clinical treatment with sodium nitrite improves the pulmonary function of rejected human lungs in an ex vivo lung perfusion model. NITRIC OXIDE-BIOLOGY AND CHEMISTRY. 110.Full Text via DOI: 10.1016/j.niox.2014.09.036
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201314-3-3 in large vessel vasculitis: A novel antigen. La Presse Médicale. 720.Full Text via DOI: 10.1016/j.lpm.2013.02.161
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2012Post-translational heme insertion into NOS and related enzymes. NITRIC OXIDE-BIOLOGY AND CHEMISTRY. S5.Full Text via DOI: 10.1016/j.niox.2012.04.020
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Review Article (Web of Science)
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2021SARS-CoV-2, ACE2 expression, and systemic organ invasion. PHYSIOLOGICAL GENOMICS. 51-60.Full Text via DOI: 10.1152/physiolgenomics.00087.2020 PMID: 33275540
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2019Mechanism and biomarkers in aortitis--a review. JOURNAL OF MOLECULAR MEDICINE-JMM. 11-23.Full Text via DOI: 10.1007/s00109-019-01838-1 PMID: 31664480
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2006Comparative genomics of the syndecans defines an ancestral genomic context associated with matrilins in vertebrates. BMC GENOMICS. 83.Full Text via DOI: 10.1186/1471-2164-7-83
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2004Compactin?a review. APPLIED MICROBIOLOGY AND BIOTECHNOLOGY. 618-624.Full Text via DOI: 10.1007/s00253-003-1553-7
Contact
full name
- Ritu Chakravarti