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Research Overview

We seek to understand the mechanisms by which heterogenous cell types orchestrate synchronous network patterns for brain computations as fundamental as memory, which may be key to understanding the origins of pathological hypersynchrony in epilepsy. Using cutting-edge in vivo approaches to home in on these mechanisms with precision, our goal is to restore circuit function with minimal side effects. As a step towards translation, we are developing new tools to uncover mechanisms of ultrasound neuromodulation and use parameter-optimized stimulation patterns to achieve cell type-specificity, but without the need for surgery or genetic manipulations.

Research Background

Dr. Farrell received his PhD from the Hotchkiss Brain Institute in Canada where he discovered that a stroke-like event occurring after seizures is responsible for long-lasting behavioral impairments and is driven by the overproduction of blood flow regulating lipids. This work won the best publication award from the Canadian Institutes of Health Research and Canadian League Against Epilepsy and has directly led to two clinical trials. He then did his postdoc with Ivan Soltesz at Stanford University, where he received the K99/R00 Pathway to Independence Award from the NIH National Institute of Neurological Disorders and Stroke to better understand how the hypothalamus controls hippocampal synchrony and epileptic seizures. He is currently an Assistant Professor of Neurology at Harvard Medical School and a faculty member of the Rosamund Stone Zander Translational Neuroscience Center and F.M. Kirby Neurobiology Center at Boston Children’s Hospital.

Selected Publications

  1. Murphy KR, Farrell JS, Gomez JL, Stedman QG, Li N, Leung S, Good CH, Qiu Z, Firouzi K, Butts Pauly K, Khuri-Yakub BT, Michaelides M, Soltesz I, de Lecea L. A tool for monitoring cell type specific focused ultrasound neuromodulation and control of chronic epilepsy. PNAS 119: e2206828119 (2022).
  2. Szabo GG, Farrell JS, Dudok B, Hou W-S, Ortiz A, Varga C, Moolchand P, Gulsever CI, Gschwind T, Dimidschtein J, Capogna M, Soltesz I. Ripple-selective GABAergic projection cells in the hippocampus. Neuron 110: 1959-1977 (2022).
  3. Farrell JS, Lovett-Barron M, Klein PM, Sparks FT, Gschwind TA, Ortiz A, Ahanonu B, Terada S, Bradbury S, Oijala M, Huang E, Dudok B, Szabo G, Schnitzer MJ, Deisseroth K, Losonczy A, Soltesz I. Supramammillary regulation of locomotion and hippocampal activity. Science 374: 1492-1496 (2021).
  4. Dong A, He K, Dudok B, Farrell JS, Guan W, Liput DJ, Puhl HL, Cai R, Duan J, Albarran E, Ding J, Lovinger DM, Li B, Soltesz I, Li Y. A fluorescent sensor for spatiotemporally resolved endocannabinoid dynamics in vitro and in vivo. Nature Biotechnology 1-12 (2021).
  5. Farrell JS, Colangeli R, Dong A, George AG, Addo-Osafo K, Kingsley PJ, Morena M, Wolff MD, Dudok B, He K, Patrick TA, Sharkey KA, Patel S, Marnett LJ, Hill MN, Li Y, Teskey GC, Soltesz I. In vivo endocannabinoid dynamics at the timescale of physiological and pathological neural activity. Neuron 109: 2398-2403 (2021).
  6. Farrell JS, Nguyen QA, Soltesz I. Resolving the micro-macro disconnect to address core features of seizure networks. Neuron 101: 1016-28 (2019).
  7. Farrell JS, Gaxiola-Valdez I, Wolff MD, David LS, Dika HI, Geeraert BL, Wang XR, Singh S, Spanswick SC, Dunn JF, Antle MC, Federico P, Teskey GC. Postictal behavioural impairments are due to a severe prolonged hypoperfusion/hypoxia event that is COX-2 dependent. eLife 5: e19352 (2016).

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Publications