- As an immunologist, my laboratory investigates broad issues related to the immune system and how it is regulated. Prior studies, in collaboration with EVMS behavior neuroscientist Larry Sanford, Ph.D, examined how escapable and inescapable stress regulated the immune response to a neuroinvasive viral pathogen related to Rabies virus. Currently, we are examining whether these two types of stress alone (no pathogen or extrinsic antigen) can activate the brain's immune system. We have demonstrated that these stressors alone activated the brain's immune system resulting in sterile neuroinflammation. Importantly, how the host perceived the stressor markedly influenced the immune response in distinct brain regions (hippocampus, prefrontal cortex, amygdala) associated with the stress response. Since stress is a common everyday occurrence, these studies suggest that our brain's may have an ongoing chronic, low-grade neuroinflammatory response which may contribute to neurodegenerative diseases that are so common in our modern society. In addition to these studies, we are using optogenetic approaches to manipulate (inhibit, stimulate) specific nuclei within the amygdala (eg., basal lateral amygdala) to clarify their role in regulating stress-induced neuroimmune responses in discrete regions of the brain that the amygdala innervates.
Richard P. Ciavarra POSITION TITLE
Department of Microbiology and Molecular Cell Biology
eRA COMMONS USER NAME
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION DEGREE
(if applicable) YEAR(s) FIELD OF STUDY
Boston University B.S. (1968) Biology/Chemistry
American University M.Sc. (197I) Immunology
Tufts University School of Medicine (Ph.D. (1978) Tumor Immunology
University of Texas, Southwestern Medical School, Dallas, TX, Postdoctoral Fellow, (1978-81) Viral Immunology/Immunogenetics
A. Positions and Honors:
Positions: PROFESSOR, Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA, 2003-present; ADJUNCT ASSOCIATE PROFESSOR, Department of Biology, ODU, 1989-present; ASSOCIATE PROFESSOR, Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk, VA, 1987-present; ASSISTANT PROFESSOR, The Biological Sciences Group, Genetics/Cell Biology Section, The University of Connecticut, Storrs, CT, 1981-1987; Cell-Mediated Cytotoxic Responses Against Viruses and Neoplastic Cells; INSTRUCTOR, Department of Microbiology, Southwestern ; PREDOCTORAL CANDIDATE, Department of Pathology, Tufts University School of Medicine, Boston, MA; Analysis of Cell-Mediated and Humoral Immune Responses Against Murine Leukemia Cells, 1973-1978; RESEARCH ASSISTANT, Department of Gastroenterology, New England Medical Center, Boston, MA; 1972.
HONORS: MEMBER, Immunological Sciences Study Section, Department of Defense Breast Cancer Research Program, 2002-present; MEMBER, Virginia Prostate Center, Eastern Virginia Medical School, Norfolk, VA, 1999-present;; National Research Service Award, 1978; NIH Pre-doctoral Fellow, Tufts University School of Medicine, 1973. American Cancer Society in 23-Grant, 1973; Charlton Fund Award, 1974; Teaching Fellowship, American University, 1971; Academic Scholarship, Boston University, 1966
B. Selected peer-reviewed publications (out of 44)
-Vesicular Stomatitis Antigens Recognized by Cytotoxic T Cells. Analysis Using Defective Interfering Particles and Reconstituted Membrane Vesicles. Richard P. Ciavarra, C.Y. Kang, and James Forman. J. Immunol., 125:336-343, 1980.
-Cytotoxic T Cells Specific for Antigens Expressed on Surface Immunoglobulin-Positive Cells. James Forman, Richard P, Ciavarra, and Ellen Vitetta. J. Exp. Med., 154:1357-1368, 1981.
-H-2L Restricted Recognition of Viral Antigens: In the H 2Ld Haplotype Anti-vesicular Stomatitis Virus Cytotoxic T Cells are Restricted Solely by H-2L. Richard P Ciavarra and James Forman. J. Exp. Med., 156:778-790, 1982.
-Use of DNA-mediated Gene Transfer to Analyze the Role of H 2Ld in Controlling the Specificity of Antivesicular Stomatitis Virus Cytotoxic T Cells. James Forman, Robert Goddenow, Leroy Hood and Richard P. Ciavarra. J. Exp. Med., 157:1261-1272, 1983
-Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS. C. D. Steel, W. K. Kim, L. D. Sanford, L.L. Wellman, S. Burnett, N. van Rooijen, R. P. Ciavarra. J Neuroimmunol. Sep 14;226(1-2):81-92, 2010
-Early gene activation initiates neuroinflammation prior to VSV neuroinvasion: Impact on antiviral responses and sleep. Richard P Ciavarra, Mayumi Machida, Marta Ambrozewicz, Lauie Wellman, Kimberly Breving, Christina Steel and Larry D Sanford, J. Neurolimmunol 303: 31-42, 2017
-Sleep and behavior during vesicular stomatitis virus induced encephalitis in BALB/cJ and C57BL/6J mice. Machida M, Ambrozewicz MA, Breving K, Wellman LL, Yang L, Ciavarra RP, Sanford LD. Brain, Behavior and Immunity, 2013
-Controllable and uncontrollable stress differentially impact pathogenicity and survival in a mouse model of viral encephalitis Ciavarra RP, Machida M, Lundberg PS, Gauronskas P, Wellman LL, Steel C, Aflatooni JO, Sanford LD J Neuroimmunol. 2018 Jun 15;319:130-141.
-Stressor Controllability and Amygdala function: Optogenetic inhibition of basal lateral amygdala suppresses neuroinflammation induced by controllable and uncontrollable stress, Richard P. Ciavarra, Laurie Wellman, Phillip Gauronkas, Wong-Ki Kim, Larry D. Sanford, Manuscript in preparation, 2020
-Consequences of Basolateral Amygdala Glutamatergic Neurotransmission on Sonic Hedgehog Signaling and Blood Brain Barrier Integrity During Stress, Richard P. Ciavarra, Laurie Wellman, Phillip Gauronkas, Larry D. Sanford, Manuscript in preparation, 2020
- Role of Sonic Hedgehog Signaling in Stress Induced Neuroinflammation
- Stresor Controllability and Dynamic Neuroimmne Interactions. We have demonstrated that stress induces cytokine gene activation in discrete regions in the brain associated with the stress response. We have further demonstrated that this results in neuroinflammation. We are currently examining what role the basal lateral amygdala plays in this response using optogenetic technology to inhibit neuronal input from the basal lateral amygdala during stress presentation.
- Neuroinvasive Vesicular Stomatitis Virus (VSV) rapidly activates multiple cytokine genes in the olfactory bulb and hippocampus. Controllable and uncontrollable stress (modeled by escapable and inescapable shock (ES and IS), respectively) amplify cytokine gene expression by augmenting type I interferon (IFN-I) and Rig-I (retinoic acid-inducible gene I) signaling through a mir146a-dependent pathway. Ingenuity Platform Analysis identified shared network nodes including IRF7, TLRs and RIG-I. ES uniquely included TLR/MYD88 and CD80 activation while IS activated several cytokines, CD40 and OAS2. Thus, stressor controllability differentially regulates neuroimmune responses to VSV with likely mediation by stress-responsive miR146a and its influence on different proinflammatory mediators.
- Role of miR146a in the Immune Response to a Neuroinvasive Viral Pathogen: We examine the role of this microRNA in regulating the neuroimmune response to a neurotropic virus related to Rabies
- Stresor Controllability and Dynamic Neuroimmne Interactions
2018Controllable and uncontrollable stress differentially impact pathogenicity and survival in a mouse model of viral encephalitis. JOURNAL OF NEUROIMMUNOLOGY. 319:130-141.
2017Modeling the peak of emergence in systems: Design and katachi. PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY. 213-241.
2017EFFECT OF SLEEP FRAGMENTATION ON THE MICROBIOME-GUT-BRAIN AXIS. SLEEP. A32-A33.
2017Early gene activation initiates neuroinflammation prior to VSV neuroinvasion: Impact on antiviral responses and sleep. JOURNAL OF NEUROIMMUNOLOGY. 303:31-42.
2014Role of peripheral immune response in microglia activation and regulation of brain chemokine and proinflammatory cytokine responses induced during VSV encephalitis. JOURNAL OF NEUROIMMUNOLOGY. 267:50-60.
2014Sleep and behavior during vesicular stomatitis virus induced encephalitis in BALB/cJ and C57BL/6J mice. BRAIN BEHAVIOR AND IMMUNITY. 35:125-134.
2012SLEEP AND ACTIVITY DURING VIRAL EENCEPHALITIS IN C57BL/6J MICE. SLEEP. A34-A34.
2010Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS. JOURNAL OF NEUROIMMUNOLOGY. 226:81-92.
2006Evaluation of immunological paradigms in a virus model: Are dendritic cells critical for antiviral immunity and viral clearance?. JOURNAL OF IMMUNOLOGY. 177:492-500.
- Professor of Microbiology and Molecular Cell Biology
- Richard P. Ciavarra, M.Sc, PH.D
recognition and awards
2002-Present- Member, Immunological Sciences Study Section, Department of Defense Breast Cancer Research Program
1999-2010- Member, Virginia Prostate Center, Eastern Virginia Medical School, Norfolk, VA
1978- National Research Service Award
1973- NIH Pre-doctoral Fellow, Tufts University School of Medicine
1973- American Cancer Society in 23-Grant
1974- Charlton Fund Award
1971- Teaching Fellowship, American University
1966- Academic Scholarship, Boston University