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Location:
Research
The DeSilva laboratory focuses on the role of neuroinflammatory responses in neurodegenerative diseases such as multiple sclerosis (MS) and Alzheimer’s disease (AD) and their impact on neuronal function. Therapeutic strategies that target the glutamate-mediated excitotoxic cascade, a critical driver of neurodegeneration, are currently being developed. These efforts aim to identify key molecular mediators that initiate cell death pathways in neurons and myelin, the insulating sheath around neuronal axons responsible for proper nerve transmission. The overall goal of these studies is to therapeutically target early mechanisms of disease for therapeutic intervention before overt neurodegeneration ensues. In parallel, the DeSilva laboratory explores innate immune responses, particularly how microglia contribute to debris clearance during brain development and how these pathways might be harnessed or reactivated to promote regeneration in the diseased brain. By understanding how immune responses affect neuronal function and repair, the DeSilva laboratory aims to develop new approaches to mitigate neurodegeneration and enhance recovery. The DeSilva laboratory combines innovative brain imaging with single cell transcriptomics to detect early signs of neurodegeneration in multiple sclerosis and Alzheimer’s disease in both white and gray matter structures in the brain. Furthermore, these studies have extended to the visual system, which relays information to and from the brain, with utilization of retinal imaging as a biomarker for neurodegeneration in the brain.
Biography
Tara M. DeSilva, PhD is an Associate Professor at the Cleveland Clinic and Case Western Reserve University School of Medicine. Dr. DeSilva received her PhD from the University of Pennsylvania and completed her postdoctoral training at Children’s Hospital Boston, Harvard Medical School. Dr. DeSilva has secured funding for neurodevelopmental disabilities, multiple sclerosis, and Alzheimer’s disease from the National Institutes of Health, National Science Foundation, Department of Defense, National Multiple Sclerosis Society, the Women’s Alzheimer’s Movement (WAM), and the pharmaceutical industry. These research endeavors have centered on four major themes: (1) neurodevelopment, (2) neuroinflammatory processes that drive disease states, (3) neuroprotective strategies to mitigate neurodegeneration and enhance recovery, and (4) the use of retinal imaging as a biomarker for neurodegeneration.
Dr. DeSilva has served on many National Institutes of Health (NIH) study sections including; Cellular and Molecular Mechanisms of Glia (CMBG), NIH Outstanding Investigator Award (R35), NINDS blueprint neurotherapeutics network (BPN) as well as the National Multiple Sclerosis Society. Dr. DeSilva also serves on the board of directors and is a consultant for several pharmaceutical companies. She is also involved in many international societies as a speaker and organizer. She participates as an organizer for ACTRIMS Young Scientist Summit every year to promote career development and education for early career scientists studying multiple sclerosis.
At a local level, Dr. DeSilva served as Chair of the Neurological and Vision Impact Research Area at the Lerner Research Institute, where she advanced interdisciplinary translational research initiatives and was instrumental in establishing a pilot funding mechanism to foster innovative collaborations. She also organizes a monthly seminar series designed to catalyze partnerships between clinical, translational, and basic neuroscience and ophthalmic research. In addition to her leadership in research development, Dr. DeSilva teaches a graduate-level ‘bench-to-bedside’ course on neurological diseases, which provides PhD students with comprehensive training in brain anatomy, neuropathological diagnosis, and mechanisms and treatments for neurodegenerative diseases. Within her own laboratory, Dr. DeSilva has built a comprehensive mentoring program that engages trainees at all levels. This structure not only provides early exposure to cutting-edge research but also cultivates leadership, teaching, and mentoring skills among more advanced trainees, thereby creating a dynamic and sustainable training environment.
Education & Professional Highlights
Appointed
2016
Medical Education - University of Pennsylvania
Biological Chemistry
Philadelphia, PA USA
Graduate School - University of Pennsylvania
Biological Chemistry
Philadelphia, PA USA
Undergraduate - Albright College
Biochemistry
Reading, PA USA
"CIMER Trained Mentor" indicates the principal investigator has completed mentorship training based on curriculum from the Center for the Improvement of Mentored Experiences in Research, aimed at advancing mentoring relationships and promoting cultural change in research.
Research
The major hallmark of demyelinating diseases such as multiple sclerosis (MS), transverse myelitis, and neuromyelitis optica (NMO) is immune cell infiltration into the central nervous system (CNS; i.e., brain, spinal cord and optic nerve), resulting in myelin destruction. Myelin is the insulation around nerve fibers (i.e., axons) that is important for the conduction of nerve impulses. Demyelination of the neuronal axon not only slows propagation of nerve impulses, but causes axonal injury, resulting in motor and vision impairments, bowel/bladder dysfunction, pain sensation, and cognitive decline. New early-stage myelin cells appear at lesion sites in demyelinating diseases, but fail to reform myelin as they would during normal development. The DeSilva lab focuses on three major areas of research:
1) Blocking immune cell infiltration into the CNS
2) Protecting the CNS during the onslaught of immune cell infiltration
3) Promoting regeneration of myelin in the CNS
Demyelinating Diseases
The most common form of MS is relapsing–remitting (RRMS), whereby exacerbations of symptoms are followed by a period of remission. A relapse is defined as a clinical event involving the onset of neurological symptoms caused by inflammation in the CNS. NMO has a similar relapsing-remitting disease progression; however, lesions are selective to the optic nerve and spinal cord and are relatively absent in the brain, unlike MS. Transverse myelitis is an acute inflammatory event selective to the spinal cord and in many cases patients are paralyzed within several hours or days. Some patients recover partially, but many patients with severe attacks have major disabilities. In some cases, transverse myelitis may present as a first relapse to develop later into MS or NMO.
Protecting the CNS
Disease-modifying therapies for MS are effective at reducing relapses, but do not eliminate them and have not been proven to slow disease progression. Therefore, therapeutic strategies to protect the CNS have clinical relevance. Using pharmacological and genetic approaches, the DeSilva lab has shown that excessive glutamate release from the system Xc- transporter expressed in microglia and macrophages causes excitotoxic damage to myelin in models of autoimmune neuroinflammation. To better understand the mechanisms driving glutamate release and its potential human clinical applications, the DeSilva lab is selectively and inducibly deleting the system Xc- transporter and its target proteins in cells of the peripheral and CNS in models of autoimmune neuroinflammation.
Blocking Immune Cell Infiltration into the CNS
While it appears that excitotoxic mechanisms play an important role in autoimmune demyelination, recent data from the DeSilva laboratory also provide evidence that glutamate contributes to immune cell infiltration into the CNS. The DeSilva lab has shown that pharmacological blockade or genetic deletion of system Xc- attenuated T cell infiltration into the CNS. Infiltration of primed T cells into the CNS is thought to initiate pathogenesis of demyelinating diseases. Furthermore, immune cells express many glutamate receptors and transporters necessary for glutamate regulation, corroborating evidence that glutamate contributes to immune cell trafficking into the CNS. The goal of this project is to understand the role of glutamate in immune cell migration and blood-brain barrier permeability in autoimmune demyelination.
Activity-Dependent Myelination and Regeneration in the CNS
The cells that form myelin are called oligodendrocytes, which are generated from oligodendrocyte progenitor cells (OPCs). Under normal conditions, OPCs mature into myelinating oligodendrocytes that ensheath nerve fibers, allowing for proper signal conduction. In pathological conditions, such as in demyelinating diseases, OPCs fail to form myelin as they normally would during development. Research in the DeSilva lab focuses on signaling factors between nerve fibers and early stage myelin-producing cells that are necessary to initiate myelination, with a special focus on the neurotransmitter glutamate. Glutamate is the primary excitatory neurotransmitter of the CNS. The DeSilva lab has shown that activity-dependent glutamate release from neurons is a necessary factor to promote myelination during development. This process may be perturbed in autoimmune neuroinflammation, where the DeSilva lab has shown that excessive glutamate release occurs through the system Xc- transporter triggering a glutamate imbalance. This work suggests that glutamate signaling must be properly activated in demyelinating diseases in order for new early stage myelin-producing cells to initiate remyelination.
Our Team
Selected Publications
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Chappel M*, Shelestak J*, Davis, D, Nemes-Baran A, Muhammad I, and DeSilva TM. Cerebellar white matter development is regulated by fractalkine-dependent microglia phagocytosis of oligodendrocyte progenitor cells. *authors contributed equally. Cell:iScience. 2025.
Shelestak John, Irfan Muhammad, DeSilva Tara M. Protocol for assessing regional pathology in the rodent optic nerve using longitudinal cryosections and cross-sectional electron microscopy. STAR Protoc. 2025. 40471791.
Kwun Audrey, Sullivan James K, Shelestak John, Merritt Kayla M, Liu Selena S, Mey Gabrielle, DeSilva Tara, Jørgensen Trine N. Sustained NPSLE-like phenotype in the absence of systemic lupus-like disease in TLR7-deficient B6.Nba2 mice. Brain Behav Immun. 2025. 40239904.
Tan Zhibing, Bussies Parker L, Sarn Nicholas B, Irfan Muhammad, DeSilva Tara, Eng Charis. Morphological and functional differences between hippocampal and cortical microglia and its impact on neuronal over-excitation in a germline Pten mutant mouse model. Neuroscience. 2025. 39984030.
Mey Gabrielle M, Evonuk Kirsten S, Shelestak John, Irfan Muhammad, Wolfe Laura M, Laye Sophia E, DeSilva Tara M. Inhibiting AMPA receptor signaling in oligodendrocytes rescues synapse loss in a model of autoimmune demyelination. iScience. 2024. 39569383.
DeSilva Tara Maria. Editorial: Animal models of multiple sclerosis: can they advance future therapies? Front Mol Neurosci. 2023. 37389092.
Mey Gabrielle M, DeSilva Tara M. Utility of the visual system to monitor neurodegeneration in multiple sclerosis. Front Mol Neurosci. 2023. 37063369.
Song Weilin, Hoppe George, Hanna Demiana, DeSilva Tara M, Sears Jonathan E. Hyperoxia Induced Hypomyelination. Biomedicines. 2022. 36672545.
DeSilva Tara M. Making myelin regenerate: Factors to consider. Curr Opin Pharmacol. 2023. 36512980.
Mey Gabrielle M, DeSilva Tara M. Endothelial-to-mesenchymal transition in multiple sclerosis: Good cells gone bad. Neuron. 2022. 36202086.
Shelestak John, Irfan Muhammad, DeSilva Tara M. Remyelinating strategies: What can be learned from normal brain development. Curr Opin Pharmacol. 2022. 36195009.
Mey Gabrielle M, Mahajan Kedar R, DeSilva Tara M. Neurodegeneration in multiple sclerosis. WIREs Mech Dis. 2023. 35948371.
Mey Gabrielle M, Evonuk Kirsten S, Chappell McKenzie K, Wolfe Laura M, Singh Rupesh, Batoki Julia C, Yu Minzhong, Peachey Neal S, Anand-Apte Bela, Bermel Robert, Ontaneda Daniel, Nakamura Kunio, Mahajan Kedar R, DeSilva Tara M. Visual imaging as a predictor of neurodegeneration in experimental autoimmune demyelination and multiple sclerosis. Acta Neuropathol Commun. 2022. 35706005.
Weber Grace E, Khrestian Maria, Tuason Elizabeth D, Shao Yvonne, Pillai Jagan, Rao Stephen, Feng Hao, Zhou Yadi, Cheng Feixiong, DeSilva Tara M, Stauffer Shaun, Leverenz James B, Bekris Lynn M. Peripheral sTREM2-Related Inflammatory Activity Alterations in Early-Stage Alzheimer's Disease. J Immunol. 2022. 35523454.
Irfan Muhammad, Evonuk Kirsten S, DeSilva Tara M. Microglia phagocytose oligodendrocyte progenitor cells and synapses during early postnatal development: implications for white versus gray matter maturation. FEBS J. 2022. 34496137.
Nemes-Baran Ashley D, DeSilva Tara M. Quantification of microglial contact and engulfment of oligodendrocyte progenitor cells in the rodent brain. STAR Protoc. 2021. 33855305.
Browne Kim, Zhang Emily, Sullivan James K, Evonuk Kirsten S, DeSilva Tara M, Jorgensen Trine N. Lupus-prone B6.Nba2 male and female mice display anti-DWEYS reactivity and a neuropsychiatric phenotype. Brain Behav Immun. 2021. 33607233.
Nemes-Baran AD, White DR, DeSilva TM. Fractalkine-Dependent Microglial Pruning of Viable Oligodendrocyte Progenitor Cells Regulates Myelination. Cell Rep. 2020. 32814050.
Evonuk KS, Doyle RE, Moseley CE, Thornell IM, Adler K, Bingaman AM, Bevensee MO, Weaver CT, Min B, DeSilva TM. Reduction of AMPA receptor activity on mature oligodendrocytes attenuates loss of myelinated axons in autoimmune neuroinflammation. Sci Adv. 2020. 6(2):eaax5936. 31934627.
Do J, Kim D, Kim S, Valentin-Torres A, Dvorina N, Jang E, Nagarajavel V, DeSilva TM, Li X, Ting AH, Vignali DAA, Stohlman SA, Baldwin WM 3rd, Min B. Treg-specific IL-27Rα deletion uncovers a key role for IL-27 in Treg function to control autoimmunity. Proc Natl Acad Sci USA. 2017. 28874534.
Evonuk KS, Moseley CE, Doyle RE, Weaver CT, DeSilva TM. Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination. J Vis Exp. 2017. 27685467.
Evonuk KS, Prabhu SD, Young ME, DeSilva TM. Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory. Brain Behav Immun. 2016. 27600185.
Cala CM, Moseley CE, Steele C, Dowdy SM, Cutter GR, Ness JM, DeSilva TM. T cell cytokine signatures: Biomarkers in pediatric multiple sclerosis. J Neuroimmunol. 2016. 27397070.
Watson JA, Bhattacharyya BJ, Vaden JH, Wilson JA, Icyuz M, Howard AD, Phillips E, DeSilva TM, Siegal GP, Bean AJ, King GD, Phillips SE, Miller RJ, Wilson SM. Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS. PLoS Genet. 2015. 26115514.
Evonuk KS, Baker BJ, Doyle RE, Moseley CE, Sestero CM, Johnston BP, De Sarno P, Tang A, Gembitsky I, Hewett SJ, Weaver CT, Raman C, DeSilva TM. Inhibition of System Xc(-) Transporter Attenuates Autoimmune Inflammatory Demyelination. J Immunol. 2015. 26071560.
Haynes RL, DeSilva TM, Li J. Mechanisms of perinatal brain injury. Neurol Res Int. 2012. 22848819.
DeSilva TM, Borenstein NS, Volpe JJ, Kinney HC, Rosenberg PA. Expression of EAAT2 in neurons and protoplasmic astrocytes during human cortical development. J Comp Neurol. 2012. 22522966.
Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM, West AB. LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci. 2012. 22302802.
DeSilva TM, Kabakov AY, Goldhoff PE, Volpe JJ, Rosenberg PA. Regulation of glutamate transport in developing rat oligodendrocytes. J Neurosci. 2009. 19535601.
Gerstner B, Lee J, DeSilva TM, Jensen FE, Volpe JJ, Rosenberg PA. 17beta-estradiol protects against hypoxic/ischemic white matter damage in the neonatal rat brain. J Neurosci Res. 2009. 19224575.
DeSilva TM, Billiards SS, Borenstein NS, Trachtenberg FL, Volpe JJ, Kinney HC, Rosenberg PA. Glutamate transporter EAAT2 expression is up-regulated in reactive astrocytes in human periventricular leukomalacia. J Comp Neurol. 2008. 18314905.
Gerstner B, DeSilva TM, Genz K, Armstrong A, Brehmer F, Neve RL, Felderhoff-Mueser U, Volpe JJ, Rosenberg PA. (2008) Hyperoxia causes maturation-dependent cell death in the developing white matter. J Neurosci. 2008. 8234901.
DeSilva TM, Kinney HC, Borenstein NS, Trachtenberg FL, Irwin N, Volpe JJ, Rosenberg PA. (2007) The glutamate transporter EAAT2 is transiently expressed in developing human cerebral white matter. J Comp Neurol. 2007. 17311320.
Careers
Research News
Dr. Tara DeSilva’s lab found new drug targets to protect the brain through researching neurodegeneration in models of multiple sclerosis.