Zsuzsanna Fabry, PhD

Portrait Zsuzsanna Fabry, PhD
Professor
CMP Graduate Program Chair
Pathology and Laboratory Medicine
Address: 
6130 MSC
1300 University Ave
Madison, WI 53706
Telephone: 
(608) 265-8716
Focus Groups: 
Immunology/Immunopathology
Neuroscience/Neuropathology
Education: 
PhD, Immunology, Budapest, Hungary
Research Summary: 
Mechanisms of neuroinflammation in autoimmunity, infection or traumas of the Central Nervous System.
Research Detail: 

For the last several years, I have focused my research program on immune, traumatic and infectious diseases of the central nervous system (CNS) that are important for public health. Our goal is to improve strategies for treating CNS inflammation.

Multiple Sclerosis (MS) project: There are a number of important CNS human diseases of poorly understood autoimmune etiology which are characterized by the presence of inflammatory cell infiltrates in the CNS and immune-mediated disruption of CNS function. One example is Multiple Sclerosis (MS), which is a chronic inflammatory disease of the CNS. The pathogenesis of this disease is very difficult to understand. Our laboratory characterized several cellular and molecular factors that are involved in the regulation of dendritic cell and T-lymphocyte adhesion, migration and activation at the brain microvessel wall an in the CNS parenchyma. The goal of our studies is to understand the role of dendritic cells and T cells in CNS autoimmune inflammatory reactions and to design new treatment for CNS inflammatory diseases. Based on our in vitro studies, my team is participating in a National Multiple Sclerosis Society (NMSS) funded clinical trial to test novel therapies to treat humans with MS.

Central Nervous System Mycobacterium tuberculosis (Mtb) infection (CNSTB) project: One of the most dangerous infectious diseases of the CNS is caused by Mycobacterium tuberculosis (Mtb) (CNSTB). The World Health Organization (WHO) declared a tuberculosis (TB) global emergency and it is estimated that today 1/3 of the world population, or approximately 2 billion people, is infected with latent TB and CNSTB is on the rise. Despite its public health importance, current understanding about the pathogenesis of this disease is outdated and limited. The goal of our work is to study the pathogenesis of CNSTB. Our overall goals are to define the mechanisms of Mtb dissemination into the CNS and the nature of protective immunity in CNSTB. Our experiments will fill the gap in our knowledge regarding the pathogenesis of CNSTB and will lead to improved strategies for treating mycobacterial infections of the CNS.

CNS Stroke project: Stroke is one of the leading causes of death and disability worldwide. Clinical studies and preclinical experimental studies suggested the contribution of inflammation in acute and long-term neuronal tissue damage following ischemic stroke; however, the mechanisms and cells involved in stroke-induced neuroinflammation are not fully understood. We study the contribution of immune cells and mediators to stroke. Based on our preliminary data, we hypothesize that IL21 critically contributes to ischemic damage in the CNS. We aim to determine if IL-21 contributes to neuronal tissue injury in the post ischemic brain by activating specific immune cells, damaging the blood-brain barrier and inducing neuronal death.

Selected Publications: 
Rayasam A, Hsu M, Hernandez G, Kijak J, Lindstedt A, Gerhart C, Sandor M, Fabry Z. Contrasting roles of immune cells in tissue injury and repair in stroke: The dark and bright side of immunity in the brain. Neurochem Int. 2017. doi: 10.1016/j.neuint.2017.02.009. PubMed PMID: 28245997.
Clarkson BD, Walker A, Harris MG, Rayasam A, Hsu M, Sandor M, Fabry Z. CCR7 deficient inflammatory Dendritic Cells are retained in the Central Nervous System. Sci Rep. 2017;7:42856. doi: 10.1038/srep42856. PubMed PMID: 28216674; PMCID: PMC5316931.
Brooks EG, Thornton JM, Ranheim EA, Fabry Z. Incorporation of Autopsy Case-Based Learning into PhD Graduate Education: a Novel Approach to Bridging the 'Bench to Bedside' Gap. Hum Pathol. 2017. doi: 10.1016/j.humpath.2017.03.006. PubMed PMID: 28315694.
Joshi DC, Zhang CL, Lin TM, Gusain A, Harris MG, Tree E, Yin Y, Wu C, Sheng ZH, Dempsey RJ, Fabry Z, Chiu SY. Deletion of mitochondrial anchoring protects dysmyelinating shiverer: implications for progressive MS. J Neurosci. 2015;35(13):5293-306. doi: 10.1523/JNEUROSCI.3859-14.2015. PubMed PMID: 25834054; PMCID: PMC4381002.
Harding JS, Rayasam A, Schreiber HA, Fabry Z, Sandor M. Mycobacterium-Infected Dendritic Cells Disseminate Granulomatous Inflammation. Sci Rep. 2015;5:15248. doi: 10.1038/srep15248. PubMed PMID: 26515292; PMCID: PMC4626772.
Harding J, Ritter A, Rayasam A, Fabry Z, Sandor M. Lymphangiogenesis is induced by mycobacterial granulomas via vascular endothelial growth factor receptor-3 and supports systemic T-cell responses against mycobacterial antigen. Am J Pathol. 2015;185(2):432-45. doi: 10.1016/j.ajpath.2014.09.020. PubMed PMID: 25597700; PMCID: PMC4305185.
Clarkson BD, Walker A, Harris MG, Rayasam A, Sandor M, Fabry Z. CCR2-dependent dendritic cell accumulation in the central nervous system during early effector experimental autoimmune encephalomyelitis is essential for effector T cell restimulation in situ and disease progression. J Immunol. 2015;194(2):531-41. doi: 10.4049/jimmunol.1401320. PubMed PMID: 25505278; PMCID: PMC4362728.
Harris MG, Hulseberg P, Ling C, Karman J, Clarkson BD, Harding JS, Zhang M, Sandor A, Christensen K, Nagy A, Sandor M, Fabry Z. Immune privilege of the CNS is not the consequence of limited antigen sampling. Sci Rep. 2014;4:4422. doi: 10.1038/srep04422. PubMed PMID: 24651727; PMCID: PMC3961746.
Clarkson BD, Walker A, Harris M, Rayasam A, Sandor M, Fabry Z. Mapping the accumulation of co-infiltrating CNS dendritic cells and encephalitogenic T cells during EAE. J Neuroimmunol. 2014;277(1-2):39-49. doi: 10.1016/j.jneuroim.2014.09.016. PubMed PMID: 25288303; PMCID: PMC4250311.
Clarkson BD, Ling C, Shi Y, Harris MG, Rayasam A, Sun D, Salamat MS, Kuchroo V, Lambris JD, Sandor M, Fabry Z. T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice. J Exp Med. 2014;211(4):595-604. doi: 10.1084/jem.20131377. PubMed PMID: 24616379; PMCID: PMC3978271.