Lindsay M De Biase
Assistant Professor, Physiology, University of California Los Angeles
Assistant Professor, Neurobiology, University of California Los Angeles
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 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 in the De Biase Lab focuses on understanding 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.
Awards and Honors
- Fellows Award for Research Excellence, NIH, 2014.
- Fellows Award for Research Excellence, NIH, 2016.
- NARSAD Young Investigator Award, Brain and Behavior Research Foundation, 2018.
- Stanley Fahn Junior Faculty Award, Parkinson's Foundation, 2021.
- NIDA Postdoctoral Fellow Mentoring Award, NIDA, 2017.
- Robert Goodman Scholars Award, Johns Hopkins School of Medicine, 2009.
- First Place, Postdoctoral poster, Annual Meeting of Greater Baltimore Chapter, Society for Neuroscience, 2014.
- Fellows Award for Research Excellence, NIH, 2015.
- Excellence in Scientific Research Award, NIDA Women’s Science Advisory Committee, 2017.
- Grant for Junior Faculty, Glen Foundation and American Foundation for Aging Research, 2019.
- Second Place; Poster awards, Winter Conference on Brain Research, Breckenridge, CO, 2016.
- Innovator Award in Cognitive Aging, McKnight Brain Research Foundation / AFAR, 2021.
- Blagburn-Blanco SV, Chappell MS, De Biase LM, DeNardo LA. Synapse-specific roles for microglia in development: New horizons in the prefrontal cortex.. Frontiers in molecular neuroscience, 2022.
- Moca EN, Lecca D, Hope KT, Etienne F, Schaler AW, Espinoza K, Chappell MS, Gray DT, Tweedie D, Sidhu S, Masukawa L, Sitoy H, Mathew R, Saban DR, Greig NH, De Biase LM. Microglia Drive Pockets of Neuroinflammation in Middle Age.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2022.
- Gray DT, De Biase LM. AMPA Receptors Exist in Tunable Mobile and Immobile Synaptic Fractions In Vivo.. eNeuro, 2021.
- Hope KT, Hawes IA, Moca EN, Bonci A, De Biase LM. Maturation of the microglial population varies across mesolimbic nuclei.. The European journal of neuroscience, 2020.
- Shen H, Marino RAM, McDevitt RA, Bi GH, Chen K, Madeo G, Lee PT, Liang Y, De Biase LM, Su TP, Xi ZX, Bonci A. 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.
- De Biase LM, Bonci A. Region-Specific Phenotypes of Microglia: The Role of Local Regulatory Cues.. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry, 2018.
- Xin W, Schuebel KE, Jair KW, Cimbro R, De Biase LM, Goldman D, Bonci A. Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling.. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018.
- De Biase LM, Schuebel KE, Fusfeld ZH, Jair K, Hawes IA, Cimbro R, Zhang HY, Liu QR, Shen H, Xi ZX, Goldman D, Bonci A. Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia.. Neuron, 2017.
- Wallace VJ, Cimbro R, Rubio FJ, Fortuno LV, Necarsulmer JC, Koivula PP, Henderson MJ, DeBiase LM, Warren BL, Harvey BK, Hope BT. Neurons Internalize Functionalized Micron-Sized Silicon Dioxide Microspheres.. Cellular and molecular neurobiology, 2017.
- De Biase LM, Bergles DE. Same players, different game: AMPA receptor regulation in oligodendrocyte progenitors.. Nature neuroscience, 2011.
- De Biase LM, Kang SH, Baxi EG, Fukaya M, Pucak ML, Mishina M, Calabresi PA, Bergles DE. 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.
- Boersma MC, Dresselhaus EC, De Biase LM, Mihalas AB, Bergles DE, Meffert MK. 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.
- De Biase LM, Nishiyama A, Bergles DE. Excitability and synaptic communication within the oligodendrocyte lineage.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010.
- Freishtat RJ, Natale J, Benton AS, Cohen J, Sharron M, Wiles AA, Ngor WM, Mojgani B, Bradbury M, Degnan A, Sachdeva R, Debiase LM, Ghimbovschi S, Chow M, Bunag C, Kristosturyan E, Hoffman EP. Sepsis alters the megakaryocyte-platelet transcriptional axis resulting in granzyme B-mediated lymphotoxicity.. American journal of respiratory and critical care medicine, 2009.