Tallie Z. Baram

Picture of Tallie Z. Baram
Bren Professor
Distinguished Professor, Pediatrics
School of Medicine
Distinguished Professor, Anatomy & Neurobiology
School of Medicine
Distinguished Professor, Neurology
School of Medicine
Danette Shepard Professor of Neurological Sciences
Director, Conte Center @ UCI
Founding Director Epilepsy Research Center (2002-2021)
Fellow, Center for Neurobiology of Learning & Memory
M.D., University of Miami, Florida
Ph.D., Weizmann Institute of Science, Israel, Neuroscience
Phone: (949) 824-1063/(949) 824-6478
University of California, Irvine
Medical Sciences I, ZOT 4475
Hewitt Research Building 3024
Mail Code: 4475
Irvine, CA 92697
Research Interests
Neuroscience, brain circuit development, stress, anhedonia, motivation, depression, learning and memory, epigenetics, paraventricular thalamus, amygdala, sex-differences, corticotropin releasing hormone, epilepsy, febrile seizures.
Academic Distinctions
2021 - current: Bren Professor, UCI
2018 - current: Distinguished Professor, UCI
1995 - current: Danette D. Shepard Endowed Chair in Neurological Sciences, UCI
Research Abstract
Tallie Z. Baram, MD, PhD is the Danette Shepard and Bren Professor of Pediatrics, Anatomy/Neurobiology, Neurology and Physiology/Biophysics at the UC-Irvine. Baram is a developmental neuroscientist and child neurologist focusing her research efforts on the influence of early-life experiences on brain maturation and the underlying mechanisms. Throughout her career, Baram has studied this topic in two broad contexts, pertaining, respectively, to stress-related and activity-dependent plasticity: a) How early-life experiences including adversity/stress promote enduring vulnerability to cognitive and emotional disorders; and b) how early-life seizures, especially those associated with fever, can convert a normal brain into an epileptic one.

A common thread of Baram’s research program is the use of multiple and trans-disciplinary technologies and levels of analysis including molecular, cellular and circuit methods and cross-species studies. She has employed these to uncover how adverse early-life experiences sculpt memory-, stress- and reward-related circuit maturation. In this context, her team has uncovered novel types of adversity in humans and rodents (unpredictable sequences of sensory signals) that contributes to aberrant circuit maturation (e.g., Birnie & Baram Science, 2022). Additionally, Baram has probed the overarching hypothesis that neuronal populations and projections expressing the stress-related peptide CRH and its signaling partners may be particularly vulnerable to early-life adversity, resulting in disrupted operations of networks that include them. This notion has led to identification of novel CRH+ reward-circuit projections, (Birnie et al., Nature Commun.2023) and assessments of established CRH-cell populations using single-cell and spatial transcriptomics.

Baram’s group has pioneered naturalistic, translationally-relevant paradigms of early-life adversity (ELA) that have been embraced world-wide, and demonstrated the causal influence of ELA on cognitive and emotional health via convergent actions of multiple mediators (including locally-synthesized CRH). More recently, through collaborative work in her Conte Center, she is applying her discoveries to humans aiming to identify important clinical questions, probe them in the lab, and then translate salient findings back to the clinic.

Baram’s work has been published in leading journals (e.g., Science, Nature Rev Neurosci, Nature Medicine, Nature Neurosci, Nature communications) and cited >35,000 times (H = 104, google scholar). She has been privileged to have her discoveries recognized, apparent from awards including the NIH NINDS Javits Merit Award, premier Research Awards of AES (2005), CNS (2013), ANA (2014) and AAN (2018), a Public Impact Award (CNLM, 2022) and Research awards from Athalie Clark Foundation (2023) UCI (2024) and ISDP (2024).

Baram strives to contribute to the scientific community by, for examples, chairing NIH study sections and involvement in editorial boards and professional organizations, including ACNP. She is passionate and committed to mentoring, with emphasis on scientific rigor and inclusivity: She is PI of a T32, and mentor of several recent K99 and F30 awardees. Many of her trainees, from diverse racial and geographical backgrounds are now contributing independently and successfully to our understanding of the brain in health and disease.

Research Description and Approach

We are interested in how early-life adversity influences the function of brain cells and circuits persistently to promote or protect from in neuropsychiatric disorders. We aim to understand the mechanisms of this neuroplasticity and employ the information to design therapies or preventative measures for stress-related disorders.

Current projects include:
a) where in the brain is early-life adversity encoded, and how does it influence adult motivated behaviors?
Our genetic tagging has pinpointed the PVT a a key ELA encoder. We use spatial transcriptomics, fiber photometry, chemo and optogenetic manipulations and circuit mapping and manipulation to identify how transient ELA changes reward and fear behaviors enduringly in a sex dependent manner

b) we identified a novel CRH and GABA expressing projection from basolateral amygdala to nucleus accumbens that underlies consequences of ELA on reward behaviors (Birnie, Nature Commun, 2023). How do GABA and CRH contribute the the projection's function?

c) we find that acute traumatic stress ( modeling mass shootings, natural disasters) impacts both spatial and fear-related memories in a sex- and estrogen-levels dependent manner, creating a PTSD-like phenotype. We use transgenic mice, epigenomics, and pharmacology to uncover the role of sex, hippocampal-estrogen levels and specific estrogen receptors in the vulnerability to acute trauma.

Other projects are ongoing. Lab members collaborate extensively and publish in outstanding journals.
Awards and Honors
2024 Senior Investigator Award, International Society of Developmental Psychobiology
2024 UCI School of Medicine Lifetime Research Achievement Award
2023 UCI Athalie Clarke Research Achievement Award
2022 Scientific Council Member, Brain & Behavior Research Foundation (BBRF)
2022 Public Impact Award, Center for the Neurobiology of Learning & Memory, UC-Irvine
2021 Bren Endowed Professor, UC-Irvine
2020 Elected Fellow, American College of Neuropsychopharmacology
2019 Elected Fellow, American Association for the Advancement of Science
2018 Fritz Dreifus Lecture, American Epilepsy Society
2018 George C. Cotzias Lectureship, American Academy of Neurology (the highest research award of the American Academy of Neurology)
2017 CURE Lectureship, University of Maryland, Baltimore
2017 Einstein Translational Medicine Lecture, Albert Einstein Sch. Med., NY
2015 Elected Member, American College of Neuropsychopharmacology
2014 Phil Dodge lectureship, Washington University St Louis
2013 Bernard Sachs Distinguished Research Award Child Neurology Society
2013 Lothman Memorial Lecturer, University of Virginia School of Medicine.
2012 Soriano Lectureship Award, American Neurological Association
2010 Outstanding Mentor Award, University of California Emeriti Association
2010-6 Chair, Board of Trustees, Lennox & Lombroso Research Trust of the American Epilepsy Society
2009 International Award for Epilepsy Research; American Society of Pharmacology and Experimental Therapeutics/ International League Against Epilepsy (ASPET-ILAE)
2008 Distinguished Scholar Lectureship, Office of the President, UCI
2006 National Institute of Health, Javits Neuroscience Merit Award
2005-2010 Epilepsy Foundation, Research Council and Professional Advisory Board.
2005 American Epilepsy Society Basic Research Recognition Award (premier worldwide prize in Epilepsy Research)
2004-2006 American Epilepsy Society, Executive Board member; elected.
2003 American Epilepsy Society, Research Initiative Award
1999 Athalie Clarke Outstanding Research Award, UCI
1995 Endowed Chair, Danette Shepard Professor in Neurological Sciences
1994 Innovative Clinical Research Award, University of Southern California
1991 Epilepsy Foundation of America, Young Investigator Award
1988 NIH NINDS Clinical Investigator Development Award, (Ko8) 1988-1993
1978 Kennedy Memorial Award (Highest Weizmann Institute PhD prize, provides funds for a postdoctoral fellowship).
1977: EMBO: Short-term International Research Award; In J. Axelrod’s lab, NIH, Bethesda
1975 Haim Weizmann Fellowship, 1975-1980
1976 Bloom fellowship for life science doctoral studies, 1976-1977
(H factor = 104; >35,000 citations, google scholar)
Selected publications:

1. Maturation of brain circuits underlying reward and stress is impacted by early-life adversity, in a cell-type and sex-specific manner

Birnie MT Short AK, de Carvalho G, Taniguchi L Gunn BG, Pham AL, Itoga CA, Xu X, Chen LY Mahler SV,i Chen Y, Baram TZ Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice. Nature communications, 2023

Birnie MT, Baram TZ Principles of emotional brain circuit maturation Science, 2022 (epub June 3)

Jessica L Bolton, Annabel K Short, Shivashankar Othy, Cassandra L Kooiker, Manlin Shao, Benjamin G Gunn, Jaclyn Beck, Xinglong Bai, Stephanie M Law, Julie C Savage, Jeremy J Lambert, Delia Belelli, Marie-Ève Tremblay, Michael D Cahalan, Tallie Z Baram. Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses. Cell Reports, 2022, 38: 13.

Annabel K Short, Christina W Thai, Yuncai Chen, Noriko Kamei, Aidan L Pham, Matthew T Birnie, Jessica L Bolton, Ali Mortazavi, Tallie Z Baram. Single-Cell Transcriptional Changes in Hypothalamic Corticotropin-Releasing Factor–Expressing Neurons After Early-Life Adversity Inform Enduring Alterations in Vulnerabilities to Stress. Biological Psychiatry Global Open Science. 2023 3:1:99-109.

Levis SC, Benzley BS, Molet J, Bolton JL, Perrone CR, Baram TZ, Mahler SV. On the early life origins of vulnerability to opioid addiction. Molec. Psych, 2019.

Bolton JL, Molet J, Regev L, Chen Y, Rismanchi N, Haddad E, Yang DZ, Obenaus A, Baram TZ. Anhedonia following early-life adversity involves aberrant interaction of anxiety and reward circuits and is reversed by partial silencing of amygdala corticotropin-releasing hormone. Biol Psychiatry, 2018, 83:137-147.

2. Early-life adversity / stress: cognitive effects across species

Short AK, Baram, TZ Adverse early-life experiences and neurologic disease: Age-old questions and novel answers. Nat Rev Neuro 2019

Davis EP, Stout SA, Molet J, Vegetabile B, Glynn LM, Sandman CA, Heins K, Stern H,
Baram TZ. Exposure to unpredictable maternal sensory signals influences cognitive development across species. PNAS, 2017, 114:10390-10395. PMC5625898.

Bonapersona V, Hoijtink H; RELACS Consortium (Abbinck, M, Baram TZ, Bolton J et al) Sarabdjitsingh RA, Joëls M. Increasing the statistical power of animal experiments with historical control data. Nat Neurosci. 2021. doi: 10.1038/s41593-020-00792-3

Ivy A, Rex C, Chen Y, Dubé C, Maras P, Grigoriadis D, Gall C, Lynch G, Baram TZ. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve activation of CRH receptors. J Neurosci, 30:13005-15, 2010.

3. Mechanisms of aberrant brain circuit maturation after early-life adversity: Epigenetics and impaired microglial function

Bolton JL, Short AK, Othy S, Kooiker CL, Shao M, Gunn BG, Beck J, Bai X, Law SM, Savage JC, Lambert JJ, Belelli D, Tremblay MÈ, Cahalan MD, Baram TZ. Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses. Cell Rep. 2022 38:110600. doi: 10.1016/j.celrep.2022.110600

Singh-Taylor A, Molet J Jian S, Korosi A, Bolton JL, Noam Y, Simeone K, Cope J Chen Y, Mortazavi A, Baram TZ. NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience. Mol Psychiatry, 2018

Bolton JL, Schulmann A, Garcia-Curran MM, Regev L, Chen Y, Kamei N, Shao M, Singh-Taylor A, Jiang S, Noam Y, Molet J, Mortazavi A, Baram TZ. Unexpected Transcriptional Programs Contribute to Hippocampal Memory Deficits and Neuronal Stunting after Early-Life Adversity. Cell Rep. 33: 108511, 2020.

McClelland S, Brennan GP, Dubé C, Rajpara S, Iyer S, Richichi C, Bernard C, Baram TZ. The transcription factor NRSF contributes to epileptogenesis by selective repression of subset of target genes. Elife 2014

4. Developmental epilepsies, including febrile seizures: the role of neuroinflammation

Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neuro, 2011, 7:31-40. An ISI highly cited paper (`1900 times)

Patterson KP, Barry JM, Curran MM, Singh-Taylor A, Brennan G, Rismanchi N, Page M, Noam Y, Holmes GL, Baram TZ. Enduring memory impairments provoked by developmental febrile seizures are mediated by functional and structural effects of neuronal restrictive silencing factor. J Neurosci, 2017.

Brennan GP, Dey D, Chen Y, Patterson KP, Magnetta E, Hall AM, Dube CM, Mei Y-T, Baram TZ. Dual and opposing roles of microRNA-124 in the generation of epilepsy are mediated through inflammatory and NRSF-dependent gene networks. Cell Reports, 2016, 14:2402-2412.

Chen K, Baram TZ, Soltesz I. Febrile Seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nature Medicine, 1999, 5:888-894.

5. Stress, epilepsy and infantile spasms

Gunn BG, Baram TZ. Stress and Seizures: Space, Time and Hippocampal Circuits. Trends Neurosci, 2017, 40:667-679.

Brunson KL, Khan N, Eghbal-Ahmadi, Baram TZ. ACTH acts directly on amygdala neurons to down-regulate corticotropin releasing hormone gene expression. Ann Neurol, 2001, 49:304-313.

Baram TZ, Mitchell WG, Tournay A, Snead OC, Hanson RA, Horton EJ. High-dose corticotropin (ACTH) versus prednisone for infantile spasms: a prospective, randomized, blinded study. Pediatrics, 1996, 97:375-379. This study, cited >400 times, is the basis of FDA approval for high-dose ACTH for infant epilepsy.

Baram TZ, Hatalski CG. Neuropeptide-mediated excitability: A key triggering mechanism for seizure generation in the developing brain. Trends Neurosci, 1998, 21:471-476.
NIH NIMH MH 96889 (P50, PI: Baram), 06/17/2013-03/31/2025, Fragmented early life environment and emotional/cognitive vulnerabilities.
NIDA 1U01DA053826 (MPI with stephen Mahler, Christie Fowler, Vivek Swarup) Dynamic epigenomic landscape of opioid abuse following early-life adversity 7/1/2022-4/30/2027
NIH NINDS NS 45540 (T32, PI: Baram), 7/01/2003 - 6/30/2029, Training grant focused on Epilepsy Research.
California Initiative for Advancing Precision Medicine. (CIAPM; PI-Baram) 7/1/2021-6/30/2025
NIH NIMH MH 132680 (R01, MPIs: Baram, Chen, Mahler) 8/1/2023 - 7/30/2028. On circuit mechanisms of reward behaviors after early-life adversity
Professional Societies
Fellow, American College of Neuropsychopharmacology (elected)
American Neurological Association (elected)
American Epilepsy Society
Society for Neuroscience
Fellow, American Association for Advancement of Science (elected)
American Academy of Neurology
Child Neurology Society
FLUX Society
International Society of Developmental Psychobiology
Other Experience
NIH CSR study sections and SEPs
President and Executive Board Member
Hewitt Foundation for Biomedical Research 2015—2024
NIH DP5 Study Section 2024
Chair and Member
NIMH K99/R00, Review Committee 2018—2024
Chair and member NIH NIMH P50 Conte Center Study Section
Joint program T32, review panel member and chair
NINDS, NIMH 2019—2020
BRAINS Review Panel
NIMH 2021
Chair Lennox/Lombroso research trust
American Epilepsy Society 2010—2016
Chair Developmental Brain Disorders study section
Graduate Programs
Cellular and Molecular Biosciences
Interdepartmental Neuroscience Program
Research Centers
Conte Center @ UCI
Center for the Neurobiology of Learning and Memory
Epilepsy Research Center
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