Kevin C. Ess, Ph.D., M.D.

Associate Professor

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Faculty Appointments
Director, Division of Pediatric Neurology Associate Professor of Pediatrics Gerald M. Fenichel Chair in NeurologyAssociate Professor of Cell & Developmental Biology
M.D., NOT APPLICABLE, University of Cincinnati, Cincinnati, OhioPh.D., Developmental Biology, University of Cincinnati, Cincinnati, OhioB.M., Music, University of Cincinnati, Cincinnati, Ohio
Office Address
MRBIII, Suite 6158
465 21st Ave South
Nashville, TN 37232-8552
Research Description
Research in my laboratory is focused on deciphering the molecular mechanisms required for normal brain development and how disruptions of these processes lead to malformations of the cerebral cortex. Children with such aberrations typically suffer from severe seizure disorders (epilepsy) as well as severe cognitive and behavioral problems such as autism. To approach these complex neurologic disorders, we have been studying tuberous sclerosis complex (TSC), a disease that prominently features cortical malformations and is caused by loss of either the TSC1 or TSC2 genes. TSC is quite prevalent and is the most common genetic cause of seizures and autism in children. Our previous investigations led us to hypothesize that the TSC1/2 genes are essential for neural progenitor cell function able to impact the differentiation and migration of neurons and glia. Abnormalities of these developmental processes may cause the cortical malformations in TSC that underlie epilepsy as well as autism in these patients. To study these complicated abnormalities of the human brain, we have generated experimental models of TSC using genetically engineered mice and zebrafish as well as in vitro progenitor cell systems including patient-derived induced pluripotent stem cells (iPSCs). The ability to manipulate Tsc1 or Tsc2 gene expression in mouse or human progenitor cells allows us to determine the role of these genes during neuronal and glial cell specification, differentiation, and migration. Our long term goal is to use these models to precisely define the molecular pathways used by the TSC1/2 genes during human brain development. This knowledge will facilitate the development of rational and hopefully more efficacious therapies for children who suffer from epilepsy or autism.
Research Keywords
cortical development, stem cells, epilepsy, autism, tuberous sclerosis
Kim SH, Speirs CK, Solnica-Krezel L, Ess KC. Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin. Dis Model Mech [print-electronic]. 2011 Mar; 4(2): 255-67. PMID: 20959633, PMCID: PMC3046101, PII: dmm.005587, DOI: 10.1242/dmm.005587, ISSN: 1754-8411.

Ess KC. Tuberous sclerosis complex: a brave new world?. Curr. Opin. Neurol. 2010 Apr; 23(2): 189-93. PMID: 20087180, PMCID: PMC2884012, DOI: 10.1097/WCO.0b013e32832c4ff5, ISSN: 1473-6551.

Ess KC. Tuberous sclerosis complex: everything old is new again. J Neurodev Disord [print-electronic]. 2009 Jun; 1(2): 141-9. PMID: 21547713, PMCID: PMC3164024, DOI: 10.1007/s11689-009-9014-y, ISSN: 1866-1955.

Ess KC. Treatment of infantile spasms in tuberous sclerosis complex: dismal outcomes but future hope?. Nat Clin Pract Neurol [print-electronic]. 2009 Feb; 5(2): 72-3. PMID: 19107107, PII: ncpneuro0994, DOI: 10.1038/ncpneuro0994, ISSN: 1745-8358.

Zeng LH, Ouyang Y, Gazit V, Cirrito JR, Jansen LA, Ess KC, Yamada KA, Wozniak DF, Holtzman DM, Gutmann DH, Wong M. Abnormal glutamate homeostasis and impaired synaptic plasticity and learning in a mouse model of tuberous sclerosis complex. Neurobiol. Dis [print-electronic]. 2007 Nov; 28(2): 184-96. PMID: 17714952, PMCID: PMC2117357, PII: S0969-9961(07)00157-X, DOI: 10.1016/j.nbd.2007.07.015, ISSN: 0969-9961.

Ess KC. The neurobiology of tuberous sclerosis complex. Semin Pediatr Neurol. 2006 Mar; 13(1): 37-42. PMID: 16818174, PII: S1071-9091(06)00013-1, DOI: 10.1016/j.spen.2006.01.009, ISSN: 1071-9091.

Ess KC, Kamp CA, Tu BP, Gutmann DH. Developmental origin of subependymal giant cell astrocytoma in tuberous sclerosis complex. Neurology. 2005 Apr 4/26/2005; 64(8): 1446-9. PMID: 15851742, PII: 64/8/1446, DOI: 10.1212/01.WNL.0000158653.81008.49, ISSN: 1526-632X.

Ess KC, Uhlmann EJ, Li W, Li H, Declue JE, Crino PB, Gutmann DH. Expression profiling in tuberous sclerosis complex (TSC) knockout mouse astrocytes to characterize human TSC brain pathology. Glia. 2004 Apr 4/1/2004; 46(1): 28-40. PMID: 14999811, DOI: 10.1002/glia.10324, ISSN: 0894-1491.

Wong M, Ess KC, Uhlmann EJ, Jansen LA, Li W, Crino PB, Mennerick S, Yamada KA, Gutmann DH. Impaired glial glutamate transport in a mouse tuberous sclerosis epilepsy model. Ann. Neurol. 2003 Aug; 54(2): 251-6. PMID: 12891680, DOI: 10.1002/ana.10648, ISSN: 0364-5134.

Wong M, Ess K, Landt M. Cerebrospinal fluid neuron-specific enolase following seizures in children: role of etiology. J. Child Neurol. 2002 Apr; 17(4): 261-4. PMID: 12088080, ISSN: 0883-0738.

Ess KC, Witte DP, Bascomb CP, Aronow BJ. Diverse developing mouse lineages exhibit high-level c-Myb expression in immature cells and loss of expression upon differentiation. Oncogene. 1999 Jan 1/28/1999; 18(4): 1103-11. PMID: 10023687, DOI: 10.1038/sj.onc.1202387, ISSN: 0950-9232.

Hutton JJ, Ess KC, Witte DP, Aronow BJ. Winner of the Theodore E. Woodward Award: c-Myb and the coordinate regulation of thymic genes. Trans. Am. Clin. Climatol. Assoc. 1996; 107: 115-24. PMID: 8725565, PMCID: PMC2376566, ISSN: 0065-7778.

Ess KC, Whitaker TL, Cost GJ, Witte DP, Hutton JJ, Aronow BJ. A central role for a single c-Myb binding site in a thymic locus control region. Mol. Cell. Biol. 1995 Oct; 15(10): 5707-15. PMID: 7565722, PMCID: PMC230821, ISSN: 0270-7306.

Ess K, Chen H, Kier A, Brackenbury R. Suppression of tumorigenicity, but not invasion, in glioblastoma/HeLa cell hybrids. J. Cell. Physiol. 1995 Mar; 162(3): 341-7. PMID: 7860642, DOI: 10.1002/jcp.1041620306, ISSN: 0021-9541.

Ess KC, Hutton JJ, Aronow BJ. Double-stranded phosphorothioate oligonucleotide modulation of gene expression. Ann. N. Y. Acad. Sci. 1994 May 5/31/1994; 716: 321-3. PMID: 8024203, ISSN: 0077-8923.

Carson R, Van Nielen D, Winzenburger P and Ess, K. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiology of Disease.