Sam Horng, MD, PhD
- ASSISTANT PROFESSOR | Neurology, Multiple Sclerosis
Research Topics:Blood-Brain Barrier, Brain Imaging, Chemokines, Cytokines, Demyelination, Immunology, Multiple Sclerosis, Neuro-degeneration/protection, Neurobiology, Neurology, Neuroscience
Dr. Horng received his B.A. in biology, summa cum laude, from Columbia University, then trained as a pre-doctoral fellow in clinical bioethics at the National Institutes of Health. He completed his MD., PhD. degree at Harvard Medical School and the Massachusetts Institute of Technology, where his graduate research investigated how early patterning events specify different sensory areas of the thalamus and cortex.
Dr. Horng completed his medical internship at Yale New Haven Hospital and his neurology residency at Mount Sinai Hospital, where he served as chief resident and was awarded an R25 Research in Residency grant from the National Institutes of Health and a Leon Levy Neuroscience Fellowship from 2015 to 2017 to study mechanisms of blood-brain barrier breakdown in inflammatory brain disease.
Dr. Horng investigates the role of specialized blood-brain barrier cells called astrocytes in controlling immune cell entry into the brain during autoimmune attack. He recently published work featured on the cover of The Journal of Clinical Investigation, demonstrating for the first time, that astrocytes act as an inducible barrier to immune cell entry in the early stages of autoimmune attack.
His laboratory is now focused on identifying specific contact-mediated interactions between astrocytes and immune cells, hypothesizing that astrocytes activate immune cells and control subsequent steps in the process of autoimmune attack. He aims to translate this work towards treatment strategies for multiple sclerosis and other CNS autoimmune diseases.
Neurology, American Board of Psychiatry and Neurology
MD, Harvard Medical School
BA, Columbia University
PhD, Massachusetts Institute of Technology
Internship, Internal Medicine, Yale-New Haven Hospital
Residency, Neurology, Mount Sinai School of Medicine
Fellowship, Multiple Sclerosis, Mount Sinai School of Medicine
K08 Mentored Clinical Scientist Research Career Development Award
Research Fellowship in Neuroscience
Arnold P. Gold Foundation’s Humanism and Excellence in Teaching Award
F30 Predoctoral NRSA Fellowship
Clinical disability in multiple sclerosis (MS) is driven by immune cell infiltration into the CNS parenchyma. Understanding the mechanisms by which CNS barrier cells regulate immune cell activation and entry during this infiltrative process may identify novel therapeutic strategies for MS and other CNS autoimmune diseases.
During CNS inflammation, immune cells traffic from the blood through a two-barrier structure termed the neurovascular unit. While many have focused on entry through the first barrier, a specialized endothelial wall known as the blood-brain barrier, less is known about how immune cells interact with the second barrier, a layer of endfoot processes extending from specialized cells called astrocytes, a barrier referred to as the glia limitans.
In MS lesions, immune cells circulate within the space between the first and second barriers, a compartment termed the perivascular space. Within this space, immune cells interact with the astrocyte endfeet and potentially receive signals that prime them for autoimmune attack. Our laboratory is interested in identifying and characterizing the signaling pathways between astrocytes and immune cells within the perivascular spaces. We are testing the hypothesis that this cross-talk regulates immune cell function prior to CNS entry and induces functional differentiation in both cell types which contributes to both the acute phase of CNS inflammation and more chronic processes of neurodegeneration.
Harel A, Horng S, Gustafson T, Ramineni A, Farber RS, Fabian M. Successful treatment of progressive multifocal leukoencephalopathy with recombinant interleukin-7 and maraviroc in a patient with idiopathic CD4 lymphocytopenia. Journal of Neurovirology 2018;.
Horng S, Therattil A, Moyon S, Gordon A, Kim K, Argaw AT, Hara Y, Mariani JN, Sawai S, Flodby P, Crandall ED, Borok Z, Sofroniew MV, Chapouly C, John GR. Astrocytic tight junctions control inflammatory CNS lesion pathogenesis. The Journal of Clinical Investigation 2017 Aug; 127(8).
Laitman BM, Asp L, Mariani JN, Zhang J, Liu J, Sawai S, Chapouly C, Horng S, Kramer EG, Mitiku N, Loo H, Burlant N, Pedre X, Hara Y, Nudelman G, Zaslavsky E, Lee YM, Braun DA, Lu QR, Narla G, Raine CS, Friedman SL, Casaccia P, John GR. The Transcriptional Activator Krüppel-like Factor-6 Is Required for CNS Myelination. PLoS Biology 2016 05; 14(5).
Chapouly C, Tadesse Argaw A, Horng S, Castro K, Zhang J, Asp L, Loo H, Laitman BM, Mariani JN, Straus Farber R, Zaslavsky E, Nudelman G, Raine CS, John GR. Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions. Brain: A Journal of Neurology 2015 Jun; 138(Pt 6).
Merlin S, Horng S, Marotte LR, Sur M, Sawatari A, Leamey CA. Deletion of Ten-m3 induces the formation of eye dominance domains in mouse visual cortex. Cerebral Cortex 2013 Apr; 23(4).
Lyckman AW, Horng S, Leamey CA, Tropea D, Watakabe A, Van Wart A, McCurry C, Yamamori T, Sur M. Gene expression patterns in visual cortex during the critical period: synaptic stabilization and reversal by visual deprivation. Proceedings of the National Academy of Sciences of the United States of America 2008 Jul; 105(27).
Horng SH, Miller FG. Placebo-controlled procedural trials for neurological conditions. Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics 2007 Jul; 4(3).
Tropea D, Kreiman G, Lyckman A, Mukherjee S, Yu H, Horng S, Sur M. Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex. Nature Neuroscience 2006 May; 9(5).
Horng SH, Sur M. Visual activity and cortical rewiring: activity-dependent plasticity of cortical networks. Progress in Brain Research 2006; 157.
Tobias ML, Barnard C, O'Hagan R, Horng SH, Rand M, Kelley DB. Vocal communication between male . Animal Behaviour 2004 Feb; 67(2).
Horng S, Grady C. Misunderstanding in clinical research: distinguishing therapeutic misconception, therapeutic misestimation, and therapeutic optimism. IRB 2003; 25(1).
Horng S, Miller FG. Ethical framework for the use of sham procedures in clinical trials. Critical Care Medicine 2003 Mar; 31(3 Suppl).
Horng S, Miller FG. Is placebo surgery unethical?. The New England Journal of Medicine 2002 Jul; 347(2).
Horng S, Emanuel EJ, Wilfond B, Rackoff J, Martz K, Grady C. Descriptions of benefits and risks in consent forms for phase 1 oncology trials. The New England Journal of Medicine 2002 Dec; 347(26).