Home | For Faculty | Help | About | Webmaster

Tallie Z. Baram

Professor, Pediatrics
School of Medicine

Professor, Anatomy & Neurobiology
School of Medicine

Professor, Neurology
School of Medicine

Scientific Director, UCI Epilepsy Program

Danette Shepard Professor in Neurological Sciences

Professor, Physiology & Biophysics
School of Medicine

Member, Center for the Neurobiology of Learning and Memory

Executive Committee, Epilepsy Research Center

M.D., University of Miami, Florida, 1980


Ph.D., Weizmann Institute of Science, Israel

Phone: (949) 824-1131
Fax: (949) 824-1106
Email:

University of California, Irvine
Medical Sciences I, ZOT 4475
Mail Code: 4475
Irvine, CA 92697


Research
Interests
Neuroscience, neurobiology, epilepsy, epileptogenesis, learning and memory, stress, corticotropin releasing hormone, hippocampus, development, programming.
   
URL www.anatomy.uci.edu/
   
Academic
Distinctions
2013: Bernard Sachs Distinguished Award for Research, Child Neurology Society.
2011: Soriano Lectureship Award of the American Neurological Association.
2010: Mentorship Award; UCI Alumni Association.
2009: Distinguished Award for Research in Epilepsy, American Society of Pharmacology and Experimental Therapeutics.
2008: Distinguished Scholar Lectureship, Office of the President, University of California.
2006: National Institute of Health NINDS, Javits Merit award.
2005: Research Recognition Award in Basic Science, the premier Epilepsy Research honor.
2005-2010: Epilepsy Foundation, Research Council and Professional Advisory Board.
2004-2006: Elected, AES Executive Board
2003: American Epilepsy Society (AES) Research Initiative Award.
1999: Athalie Clarke Excellence in Research Award, University of California-Irvine.
1995-current: Danette D. Shepard Endowed Chair in Neurological Sciences, University of California-Irvine.
1991: American Epilepsy Society Young Investigator Research Award
1988-1993: NINDS: Career Development Research Award (KO8)
1978-1980: Kennedy Postdoctoral Award (highest Weizmann Institute Graduate Award)
1977: EMBO: Short-term International Research Award; In J. Axelrod’s lab, NIH, Bethesda
1976-1977: Bloom Fellowship for doctoral studies, life sciences, Weizmann Institute of Science
   
Research
Abstract
Research Description and Approach

We are interested in how early-life experience (specifically stress or seizures) influence the function of brain cells persistently ('re-program' them), to promote or protect from in human disease. We aim to understand the mechanisms of this neuroplasticity and employ the information to design therapies for prevention/treatment of stress-related disorders and epilepsy, respectively.

Lab members use molecular biology, transgenic, epigenetic and in vitro and in vivo imaging methods. We use both in animal models where genes are controlled in time and space and in vitro systems including slice cultures and dissociated neurons. We study:
(a) how seizures induce large-scale, epigenetic changes in gene transcription programs in neurons, and the mechanisms of this coordinate transformation of normal neurons into 'epileptic' ones.

(b) how early life stress or enriched experience modify gene expression and synaptic function in the hippocampus and in specific hypothalamic neurons, predisposing to- or protecting from-cognitive and emotional stress related disorders including depression. Students use genetically modified mice where hippocampal neurons are visible to examine in real time how stress and hormones influence dendritic spine dynamics and neuronal structure. They test how these changes influence learning and memory. Mechanisms of experience- induced changes in neuronal gene expression (programming) are studied using neuroanatomical, molecular biology and physiological approaches.

Lab members collaborate extensively, and publish in outstanding journals.
   
Publications Selected peer-reviewed publications grouped by topic, in reverse chronology (of >170 peer reviewed):

NEUROBIOLOGY OF STRESS, LEARNING AND MEMORY AND THE CELLULAR MACHINERY OF CRH

Maras PM, Molet J, Chen Y, Rice C, Ji SG, Solodkin A, Baram TZ. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress. Mol Psychiatry 2014. (IF = 15)

Vogel-Ciernia A, Barrett RM, Matheos DP, Kramár E, Azzawi S, Chen Y, Magnan CN, Zeller M, Sylvain A, Haettig J, Jia Y, Tran A, Dang R, Post RJ, Chabrier M, Babayan A, Wu JI, Crabtree GR, Baldi P, Baram TZ, Lynch G, Wood MA. The neuron-specific chromatin regulatory subunit BAF53b is necessary for synaptic plasticity and memory. Nat Neurosci, 16:552-61, 2013.

Andres AL, Regev L, Phi L, Seese RR, Chen Y, Gall CM, Baram TZ. NMDA Receptor Activation and Calpain Contribute to Disruption of Dendritic Spines by the Stress Neuropeptide CRH. J Neurosci, 33:16945-60, 2013.

Chen Y, Kramár EA, Chen LY, Babayan AH, Andres AL, Gall CM, Lynch G, Baram TZ. Impairment of synaptic plasticity by the stress mediator CRH involves selective destruction of thin dendritic spines via RhoA signaling. Mol Psychiatry, 18:485-96, 2013. (IF = 15.5)

Baram TZ, Davis EP, Obenaus A, Sandman CA, Small SL, Solodkin A, Stern H. Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders. Am J Psychiatry, 169:907-15, 2012.

Maras PM, Baram TZ. Sculpting the Hippocampus from within: Stress, Spines, and CRH. Trends Neurosci, 35:315-24, 2012.

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.

Chen Y, Rex CS, Rice CJ, Dubé CM, Gall CM, Lynch G, Baram TZ. Correlated memory defects and hippocampal dendritic spine loss after acute stress involve corticotropin-releasing hormone signaling. PNAS, 29:13123-28, 2010.

Korosi A, Shanabrough M, McClelland S, Liu ZW, Borok E, Gao XB, Horvath TL, Baram TZ. Early-life experience reduces excitation to stress-responsive hypothalamic neurons and re-programs the expression of corticotropin releasing hormone. J Neurosci, 30:703-13, 2010.

Joëls M, Baram TZ. The Neuro-symphony of Stress. Nature Reviews Neuroscience, 10:459-66, 2009. (IF = 29)

Chen Y, Dubé C, Rice CJ, Baram TZ. Rapid loss of dendritic spines after stress involves derangement of spine dynamics by corticotropin-releasing hormone. J Neurosci, 28:2903-11, 2008.

Fenoglio KA, Chen Y, Baram TZ. Neuroplasticity of the hypothalamic-pituitary-adrenal (HPA) axis early in life requires recurrent recruitment of stress-regulating brain regions. J Neurosci, 26:2434-42, 2006.

Chen Y, Fenoglio KA, Dube CM, Grigoriadis DE, Baram TZ. Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent. Mol Psychiatry, 11:992-1002, 2006. (IF = 15.5)

Fenoglio KA, Brunson KL, Baram TZ. Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects. Front Neuroendocrinol, 27:180-92, 2006. (IF = 12.7)

Brunson KL, Kramár E, Lin B, Chen Y, Colgin LL, Yanagihara TL, Lynch G, Baram TZ. Mechanisms of late-onset cognitive decline after early life stress. J Neurosci, 25:9328-38, 2005.

Chen Y, Bender RA, Brunson KL, Pomper J, Grigoriadis DE, Wurst W, Baram TZ. Modulation of dendritic differentiation by corticotropin-releasing factor in developing hippocampus. PNAS, 101:15782-87, 2004.

Avishai-Eliner S, Brunson KL, Sandman CA, Baram TZ. ‘Stressed out?’ Or in (utero). Trends Neurosci, 25:518-24, 2002.

Roozendaal B, Brunson KL, Holloway B, McGaugh JL, Baram TZ. Involvement of stress-released CRH in the basolateral amygdala in regulating memory consolidation. PNAS, 99:13908-13, 2002.

Brunson KL, Eghbal-Ahmadi M, Roland R, Chen Y, Baram TZ. Long-term progressive hippocampal cell loss and dysfunction induced by early-life stress. PNAS, 98:8856-61, 2001.

Brunson KL, Khan N, Eghbal-Ahmadi, Baram TZ. ACTH acts directly on amygdala neurons to down-regulate corticotropin releasing hormone gene expression. Ann Neurol, 49:304-13, 2001.

Chen Y, Bender R, Frotscher M, Baram TZ. Novel and transient populations of corticotropin-releasing hormone-expressing neurons in developing hippocampus suggest unique functional roles: a quantitative spatio-temporal analysis. J Neurosci, 21:7171-81, 2001.

Eghbal-Ahmadi M, Avishai-Eliner S, Hatalski CG, Baram TZ. Differential regulation of the expression of corticotropin releasing factor receptor type 2 (CRF2) in hypothalamus and amygdala of the immature rat by sensory input and food intake. J Neurosci, 19:3982-91, 1999.

Baram TZ, Hatalski CG. Neuropeptide-mediated excitability: A key triggering mechanism for seizure generation in the developing brain. Trends Neurosci, 21:471-76, 1998.


EPILEPSY, SEIZURES, EPILEPTOGENESIS AND UNDERLYING MECHANISMS

Noam Y, Ehrengruber MU, Koh A, Feyen P, Manders EM, Abbott GW, Wadman WJ, Baram TZ. Filamin A Promotes Dynamin-dependent Internalization of Hyperpolarization-activated Cyclic Nucleotide-gated Type 1 (HCN1) Channels and Restricts Ih in Hippocampal Neurons. J Biol Chem, 2014.

Marcelin B, Liu Z, Chen Y, Lewis AS, Becker A, McClelland S, Chetkovich DM, Migliore M, Baram TZ, Esclapez M, Bernard C. Dorsoventral differences in intrinsic properties in developing CA1 cells. J Neurosci, 32:3736-47, 2012.

Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol, 7:31-40, 2011.

McClelland S, Flynn C, Dubé C, Richichi C, Zha QQ, Ghestem A, Esclapez M, Bernard C, Baram TZ. Neuron-restrictive silencer factor-mediated hyperpolarization activated, cyclic nucleotide gated channelopathy in experimental temporal lobe epilepsy. Ann Neurol, 70:454-65, 2011.

Noam Y, Bernard C, Baram TZ. Towards an integrated view of HCN channel role in epilepsy. Curr Opin Neurobiol, 21:873-79, 2011.

Dubé CM, Ravizza T, Hamamura M, Zha Q, Keebaugh A, Fok K, Andres AL, Nalcioglu O, Obenaus A, Vezzani A, Baram TZ. Epileptogenesis provoked by prolonged experimental febrile seizures: mechanisms and biomarkers. J Neurosci, 30:7484-94, 2010.

Noam Y, Zha Q, Phan L, Wu RL, Chetkovich DM, Wadman WJ, Baram TZ. Trafficking and surface expression of the hyperpolarization-activated nucleotide-gated channels in hippocampal neurons J Biol Chem, 285:14724-36, 2010.

Lewis AS, Schwartz E, Chan CS, Noam Y, Shin M, Baram TZ, Macdonald RL, Chetkovich DM. Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function. J Neurosci, 29:6250-65, 2009.

Dube C, Brewster AL, Richichi, C, Zha QQ, Baram TZ. Fever, febrile seizures and epilepsy. Trends Neurosci, 30:490-96, 2007.

Bender RA, Kirschstein T, Kretz O, Brewster AL, Richichi C, Rüschenschmidt C, Shigemoto R, Beck H, Frotscher M, Baram TZ. Localization of HCN1 channels to presynaptic compartments: novel plasticity that may contribute to hippocampal maturation. J Neurosci, 27:4697-706, 2007.

Dubé C, Richichi C, Bender RA, Chung G, Litt B, Baram TZ. Temporal lobe epilepsy after experimental prolonged febrile seizures: prospective analysis. Brain, 129:911-22, 2006.

Dubé C, Vezzani A, Behrens M, Bartfai T, Baram TZ. Interleukin 1? contributes to the generation of experimental febrile seizures. Ann Neurol, 57:152-55, 2005.

Dubé C, Yu H, Nalcioglu O, Baram TZ. Serial magnetic resonance imaging (MRI) after experimental febrile seizures: altered T2 signal does not signify neuronal death. Ann Neurol, 56:709-14, 2004.

Baram TZ. Long-term neuroplasticity and functional consequences of single versus recurrent early-life seizures. Ann Neurol, 54:701-05, 2003.

Bender RA, Soleymani SV, Brewster AL, Nguyen ST, Beck H, Mathern GW, Baram TZ. Enhanced expression of specific HCN in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus. J Neurosci, 23:6826-36, 2003.

Santoro B, Baram TZ. The multiple personalities of the H Channels. Trends Neurosci, 26:550-54, 2003.

Sullivan PG, Dubé C, Dorenbos K, Steward O, Baram TZ. Mitochondrial uncoupling protein-2 contributes crucially to the resistance of immature brain to excitotoxic neuronal death. Ann Neurol, 53:711-17, 2003.

Brewster A, Bender RA, Chen Y, Eghbal-Ahmadi M, Dubé C, Baram TZ. Developmental febrile seizures modulate hippocampal gene expression of HCN channels in an isoform and cell-specific manner. J Neurosci, 22:4591-99, 2002.

Chen K, Aradi I, Eghbal-Ahmadi M, Baram TZ, Soltesz I. Persistently modified h-channels after complex febrile seizures convert seizure-induced enhancement of inhibition into hyperexcitability. Nature Medicine, 73:331-77, 2001.

Dubé C, Chen K, Eghbal-Ahmadi M, Brunson K, Soltesz I, Baram TZ. Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long-term. Ann Neurol, 47:336-44, 2000.

Chen K, Baram TZ, Soltesz I. Febrile Seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nature Medicine, 5:888-94, 1999.

Toth Z, Yan XX, Heftoglu S, Ribak CE, Baram TZ. Seizure-induced neuronal injury: vulnerability to febrile seizures in an immature rat model. J Neurosci, 18:4285-94, 1998.

Baram T, Koch Y, Hazum E, Fridkin M. Gn-RH in milk. Science, 198:300-02, 1977.

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, 97:375-9, 1996.
   
Grants NIH NIMH MH 96889 (P50, PI: Baram), 06/17/2013-04/30/2018, Fragmented early life environment and emotional/cognitive vulnerabilities.
   
NIH NINDS NS 35439 (R37, PI: Baram), 4/01/1997-06/30/2014, Febrile seizure model: Neuronal injury and mechanisms. Javits Merit Award, 8/2006-
   
NIH NINDS NS 45540 (T32, PI: Baram), 7/01/2003 - 6/30/2019, Training grant for post-doctoral fellows focused on Epilepsy Research.
   
NIH NIMH MH 73136 (RO1, PI: Baram), 12/01/1999-02/28/15, Early life experience and plasticity: Role of CRH.
   
NIH NINDS NS 28912 (RO1, PI: Baram), 3/1/1992- 11/30/2014, CRH in stress-induced hippocampus neuroplasticity.
   
Professional
Societies
Society for Neuroscience
American Academy of Neurology
American Neurological Association (elected)
American Academy of Pediatrics
American Epilepsy Society
Child Neurology Society
Endocrine Society
American Association for Advancement of Science
   
Graduate Programs Interdepartmental Neuroscience Program

Cellular and Molecular Biosciences

   
Research Centers Epilepsy Research Center
   
Conte Center @ UCI, Director
   
Center for Learning and Memory
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=4479
   
Last updated 04/17/2014