Luke Healy, PhD
Dr. Healy’s lab works on the cellular and molecular mechanisms of neuroinflammation with a particular focus on the innate immune cell of the brain, the microglia. Microglia are the first cells to react and respond to any pathological changes in the CNS, placing them at the center of all neurological disease. The advent of genome-wide association studies has now clearly identified mutations in multiple genes highly expressed in microglia that infer risk for the development of several, classically non-neuroinflammatory diseases of the CNS. These include Huntington’s, Parkinson’s, and Alzheimer’s disease. Understanding the resting or basal functions of these microglia cells is thus central in understanding their role in disease.
Dr. Healy’s lab works primarily with human microglia derived from cultured brain tissue, removed during the course of surgical treatment of temporal lobe epilepsy. Given the difficulty of obtaining such samples in abundance, however, the lab has established a method for the generation of microglia from inducible pluripotent stem cells (iPSCs) in less than 5 weeks. This highly efficient method enables high purity and robust scalability making it an ideal platform to screen libraries for compounds with anti-inflammatory activities in a population of patient-specific, disease-relevant cells.
Dr. Healy’s work currently focuses on building a comprehensive transcriptomic and functional picture of the human spinal cord and brain microglia. His lab studies the homeostatic functions of microglia, with a focus on phagocytosis, to understand how the function of phagocytosis is affected by disease relevant stimuli and how it may be targeted pharmacologically to combat chronic microglial inflammation. The lab is also developing inducible microglia from MS and neurodegenerative disease patient-derived iPSCs to examine how microglia can provide a link between genetic risk factors, inflammation and neurodegenerative disease-associated phenotypes.
Dr. Luke Healy obtained his B.Sc. (Hons) in Neuroscience from the University College of Cork (Ireland) and undertook his doctoral work at Trinity College Institute of Neuroscience in Trinity College Dublin under the supervision of Professor Kumlesh Dev. His PhD focused on the pharmacologic effects of a new multiple sclerosis disease-modifying therapy, Gilenya, on human astrocytes. In 2014 Dr. Healy undertook his postdoctoral training in the laboratories of Drs. Jack Antel and Amit Bar-Or at the Montreal Neurological Institute (MNI), McGill University (Montreal, Canada) where he focused on the role of human myeloid cell populations in the pathogenesis of multiple sclerosis. His work using monocyte-derived-macrophages from patient populations in addition to primary human adult microglia derived from surgically resected tissues has shed light on the molecular processes of phagocytic uptake of myelin debris by these cell types. He joined The Neuro as an assistant professor in the Department of Neurology and Neurosurgery in March 2018.
Abud, EM, Ramirez, R, Martinez, N, Healy, LM, Nguyen, C, Newman, SA, Yeromin, AV, Scarfone, V, Marsh, S, Fimbres, C, Caraway, C, Fote, G, Gylys, K, Cahalan, M, Cummings, B, Antel, JP, Mortazavi, A, Carson, M, Poon, W, Blurton-Jones, M. Generation of human microglia-like cells to study neurological disease. 2017. Neuron. 94(2):278-293.
Antel JP, Lin YH, Cui QL, Pernin F, Kennedy TE, Ludwin SK, Healy LM. Immunology of oligodendrocyte precursor cells in vivo and in vitro. Journal of Neuroimmunology. 2018. S0165-5728(18)30121-8.
Healy, LM, Perron, G, Bell, SC, Michell-Robinson, MA, Won, SY, Salmon, C, Rezyk, A, McBride, H, Ludwin, S, Moore, CS, Bar-Or, A and Antel JP. MerTK as a functional regulator of myelin phagocytosis in human myeloid cells. 2016. Journal of Immunology. 96(8):3375-84
Healy, LM, Won, SY, Jang JH, Lin, YH, Aljarallah, S, Bar-Or, A and Antel, JP. MerTK-mediated regulation of myelin phagocytosis by macrophages generated from patients with MS 2017. Neurology: Neuroimmunology and Neuroinflammation. 4 (6) e402
Healy LM, Perron G, Won SY, Rao VTS, Guiot MC, Moore C, Bar-Or A, Antel JP. Differential transcriptional response profiles in human myeloid cell populations. Clinical Immunology. 2018. 189:63-74.