De Biase, Lindsay

Titles

Assistant Professor, Physiology

Member, Molecular, Cellular & Integrative Physiology GPB Home Area

Neuroscience GPB Home Area

Contact Information

Email
LDeBiase@mednet.ucla.edu
Address

Mailing Address:

77-200F CHS
10833 Le Conte Ave
Los Angeles, CA 90095
UNITED STATES

Biography

Lindsay M. De Biase, PhD is an Assistant Professor in the Department of Physiology in the David Geffen School of Medicine at UCLA. She received her B.S in Cellular, Molecular, and Developmental Biology at Yale University in 2003. Upon graduation, she worked as a research assistant with Drs. Eric Hoffman and Robert Frieshtat at the Children’s National Medical Center in Washington D.C. investigating gene expression changes associated with amyotrophic lateral sclerosis (Lou Gehrig’s disease) and acute lung injury. Dr. De Biase then entered the Neuroscience Graduate Program at Johns Hopkins School of Medicine where she earned her Ph.D. working with Dr. Dwight Bergles on synaptic signaling from neurons to oligodendrocyte precursor cells (OPCs). During her thesis work, Dr. De Biase developed novel approaches for electrophysiological analysis of neuron-OPC synapses and discovered that OPC synaptic connectivity varies across brain regions and is rapidly lost as the cells mature into oligodendrocytes, consistent with the hypothesis that this signaling acts as a brake on OPC differentiation. Dr. De Biase then completed postdoctoral training with Dr. Antonello Bonci at the National Institute on Drug Abuse, where she discovered that microglia in distinct basal ganglia nuclei exhibit regionally-specialized phenotypes, overturning the widespread belief that these cells are equivalent throughout the CNS. Her work also provided evidence that local regulatory cues play a critical role in shaping microglial diversity. She joined UCLA's faculty in the fall of 2018.

Research Interests

Causes and consequences of microglial regional specialization within basal ganglia circuits.

Microglia are dynamic, macrophage-like cells within the CNS. In disease and injury contexts, they undergo dramatic changes in cell phenotype that result in powerful neuroprotective and/or neurotoxic effects. In the healthy brain, microglia remove cellular debris and pathogens from surrounding tissue and can modulate both neuronal membrane properties and synapses, positioning these cells as key contributors to both physiological and pathological circuit function. 

Microglia are not equivalent throughout the brain and exhibit specialized phenotypes in different nuclei of the basal ganglia (BG), circuits involved in reward and motivation. We know almost nothing about the potential impact of this regional microglial variation on function and resilience of surrounding neurons. Work in the De Biase lab focuses on three overarching questions: 1) How does microglial variation impact synaptic function of BG neurons and associated reinforcement-driven behaviors? 2) How does basal phenotype shape microglial injury responses and influence susceptibility of BG neurons to damage? 3) What regulatory cues instruct basal phenotypes of BG microglia? We pursue these questions using multiple technical approaches including slice electrophysiology, advanced imaging, and molecular biology.

An overarching goal of this research program is to promote innovative approaches to treating CNS circuit dysfunction and disease. Microglia are ubiquitous, capable of self-renewal, highly plastic, and can be influenced from the periphery, making them highly attractive targets for therapeutic interventions in a broad range of pathological contexts. Information obtained from these research efforts will be particularly relevant for pathological alterations that impact BG circuits, such as addiction and other psychiatric illness, neurodegeneration, toxic poisoning, and focal inflammatory conditions.


Publications

A selected list of publications:

Shen Hui, Marino Rosa Anna M, McDevitt Ross A, Bi Guo-Hua, Chen Kai, Madeo Graziella, Lee Pin-Tse, Liang Ying, De Biase Lindsay M, Su Tsung-Ping, Xi Zheng-Xiong, Bonci Antonello   Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice Proceedings of the National Academy of Sciences of the United States of America, 2018; 115(49): E11532-E11541.
De Biase Lindsay M, Bonci Antonello   Region-Specific Phenotypes of Microglia: The Role of Local Regulatory Cues The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 2018; 1073858418800996.
Xin Wendy, Schuebel Kornel E, Jair Kam-Wing, Cimbro Raffaello, De Biase Lindsay M, Goldman David, Bonci Antonello   Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018; 1073858418800996.
Wallace Veronica J, Cimbro Raffaello, Rubio F Javier, Fortuno Lowella V, Necarsulmer Julie C, Koivula Pyry P, Henderson Mark J, DeBiase Lindsay M, Warren Brandon L, Harvey Brandon K, Hope Bruce T   Neurons Internalize Functionalized Micron-Sized Silicon Dioxide Microspheres Cellular and molecular neurobiology, 2017; 37(8): 1487-1499.
De Biase Lindsay M, Schuebel Kornel E, Fusfeld Zachary H, Jair Kamwing, Hawes Isobel A, Cimbro Raffaello, Zhang Hai-Ying, Liu Qing-Rong, Shen Hui, Xi Zheng-Xiong, Goldman David, Bonci Antonello   Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia Neuron, 2017; 95(2): 341-356.e6.
De Biase Lindsay M, Bergles Dwight E   Same players, different game: AMPA receptor regulation in oligodendrocyte progenitors Nature neuroscience, 2011; 14(11): 1358-60.
De Biase Lindsay M, Kang Shin H, Baxi Emily G, Fukaya Masahiro, Pucak Michele L, Mishina Masayoshi, Calabresi Peter A, Bergles Dwight E   NMDA receptor signaling in oligodendrocyte progenitors is not required for oligodendrogenesis and myelination The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(35): 12650-62.
Boersma Matthew C H, Dresselhaus Erica C, De Biase Lindsay M, Mihalas Anca B, Bergles Dwight E, Meffert Mollie K   A requirement for nuclear factor-kappaB in developmental and plasticity-associated synaptogenesis The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011; 31(14): 5414-25.
De Biase Lindsay M, Nishiyama Akiko, Bergles Dwight E   Excitability and synaptic communication within the oligodendrocyte lineage The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010; 30(10): 3600-11.
Freishtat Robert J, Natale Joanne, Benton Angela S, Cohen Joanna, Sharron Matthew, Wiles Andrew A, Ngor Wai-Man, Mojgani Bahar, Bradbury Margaret, Degnan Andrew, Sachdeva Reecha, Debiase Lindsay M, Ghimbovschi Svetlana, Chow Matthew, Bunag Clarice, Kristosturyan Ervand, Hoffman Eric P   Sepsis alters the megakaryocyte-platelet transcriptional axis resulting in granzyme B-mediated lymphotoxicity American journal of respiratory and critical care medicine, 2009; 179(6): 467-73.
Freishtat Robert J, Mitchell Lindsay W, Ghimbovschi Svetlana D, Meyers Samuel B, Hoffman Eric P   NKG2A and CD56 are coexpressed on activated TH2 but not TH1 lymphocytes Human immunology, 2005; 66(12): 1223-34.