Education and Training
- University of Toledo, BS, Biology, 2003
- University of Maryland Baltimore, Ph.D., Neuropharmacology, 2011
- University of Maryland School of Medicine, Postdoctoral training, Psychoneuroimmunology, 2011-2015
As part of the Laboratory in Behavioral neuroimmunology, the primary focus of my research is the role of neuroimmune interactions between the adaptive immune system and the central nervous system in the development of psychiatric disorders, to include depression and anxiety, as well as schizophrenia. Like many neuroscientists, I am intrigued by how the brain works, as well as why and how function becomes impaired, whether as a consequence of genetics, environment, or both. The scope of my research spans three main components: 1) the role of the adaptive immune system in behavioral responses to stress; 2) inflammation and depression; and 3) neuroimmune interactions in neurodevelopment. This research incorporates the use of various models of stress or disease in both mice and rats, as well as human post-mortem studies, and a variety of cellular and molecular techniques and behavioral assessments. My current goal is to establish an indepentent research program to investigate neuroimmune interactions across the lifespan and their impact on brain function and behavior, with the primary hypothesis that immune regulation of neuro- and gliogenesis is necessary for normal brain development and homeostasis. Subsequently, immune dysregulation, particularly during critical periods of brain development, may contribute to the onset of various psychiatric disorders.
Using rodents to model aspects of human psychiatric disorders, such as PTSD and schizophrenia, I examine how the adaptive immune system, and T cells specifically, can impact neurodevelopment, stress responsivity, emotionality, and cognitive function. This research has allowed for identification of CD8+ T cells as modulators of cytokine responses to stress and recognition of CD4+ T cells in promoting adaptive learning and memory processes. Recently, my work also revealed a critical role for the adaptive immune system in the development of social behavior, spatial memory, and cognitive flexibility during adolescence. Finally, using a combination of rodent and human studies, I have also been working to elucidate how the immune system modulates tryptophan metabolism, resulting in dysregulation of the kynurenine pathway as part of a Silvio O. Conte center grant to Dr. Robert Schwarcz (Project 2 PI: Dr. Leonardo Tonelli) at the Maryland Pscyhiatric Research Center.
psychoneuroimmunology, T cells, stress, behavior, hippocampus, neurogenesis
Clark SM, Notarangelo FM, Li X., Chen S, Schwarcz R, Tonelli LH. Maternal immune activation in rats blunts brain cytokine and kynurenine pathway responses to a second immune challenge in early adulthood. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 8;89:286-298.
Clark SM, Song C, Li X, Keegan AD, Tonelli LH. CD8(+) T cells promote cytokine responses to stress. Cytokine. 2019. Jan; 113:256-264.
Clark SM, Soroka JA, Song C, Li X, Tonelli LH. CD4+ T cells confer anxiolytic and antidepressant-like effects, but enhance fear memory processes in Rag2-/- mice. Stress. 2016 May;19(3):303-11.
Clark SM, Pocivavsek A, Nicholson JD, Notarangelo FM, Langenberg P, McMahon RP, Kleinman JE, Hyde TM, Stiller J, Postolache TT, Schwarcz R, Tonelli LH. Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals. J Psychiatry Neurosci. 2016 Apr 11;41(4):150226.
Clark SM, Sand, J, Francis, T., Nagaraju, A, Michael, KC, Keegan, AD, Kusnecov, A, Gould, TD, and Tonelli, LH. Immune status influences fear and anxiety responses in mice after acute stress exposure. Brain Behav Immun. 2014. May; 38:192-201.
Clark S, Schwalbe J, Stasko MR, Yarowsky PJ, Costa AC. Fluoxetine rescues deficient neurogenesis in hippocampus of the Ts65Dn mouse model for Down syndrome. Exp Neurol. 2006 Jul; 200(1):256-61.
2002 The Honor Society of Phi Kappa Phi, University of Toledo
2003 NIH Training Grant for Neuroscience
2013 Outstanding Trainee Poster Presentation, Dept. Psychiatry Annual Research Day, University of Maryland
2014 Outstanding Trainee Poster Presentation, $1500 Travel Award, Dept. Psychiatry Annual Research Day, University of Maryland
2018 Virginia Huffer Excellence Award