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Uthayashanker Ezekiel, Ph.D., MB(ASCP)

Tenured Professor
Clinical Health Sciences

Education

  • Post-Doctoral Fellowship, Yale University
  • Post-Doctoral Fellowship, University of Chicago
  • Ph.D. in Microbiology, Saint Louis University
  • Master of Science in Integrated Biology, Madurai Kamaraj University
  • Bachelor of Science in Zoology, Madurai Kamaraj University

Research Interests

The Ezekiel Lab investigates the role of C-terminal-binding proteins (CtBPs) in neurodevelopment. CtBPs, a highly conserved protein family comprising CtBP1 and CtBP2, function primarily as transcriptional corepressors. Studies in both invertebrate and vertebrate systems have shown that transcriptional repressors containing PLDLS/PXDLS motifs recruit CtBPs to mediate gene repression.

While CtBPs were not previously associated with neurological disorders, recent discoveries link de novo CTBP1 mutations to hypotonia, cerebellar ataxia, developmental delay, and tooth-enamel defect syndrome (HADDTS), establishing a direct role for CtBP1 in neurodevelopmental disease.

To explore these mechanisms, we employ patient-derived and genome-edited isogenic induced pluripotent stem cell (iPSC) lines, differentiated into neural stem cells and neurons, to examine how CTBP1 mutations disrupt neurodevelopmental processes. Genome-wide transcriptomic analyses of isogenic mutant cell lines have revealed key transcriptional factors dysregulated by CTBP1 mutations.

Our current efforts focus on deciphering how pathogenic CTBP1 alleles contribute to disease phenotypes using isogenic iPSCs differentiated into cerebellar granule cells, where CTBP1 is highly expressed. In parallel, we are developing 3D organoid models to further investigate the mechanisms by which CTBP1 pathogenic alleles drive HADDTS. By uncovering these molecular pathways, we aim to identify strategies to ameliorate disease manifestations in HADDTS.

Publications and Media Placements

  • Lee S, Vijayalingam S, Klotz E, Dedert C, Xu F, Chinnadurai G and Ezekiel UR. Isogenic iPSC-Derived CTBP1 Mutant Neuronal Cells Exhibit Neurodevelopmental Defects. Frontiers in Neuroscience.2025, Manuscript ID: 1695464
  • Lee S, Ezekiel UR. Using Allen Brain Cell Atlas of the Human Brain to Gain Insights into the C-Terminal Binding Protein 1 (CTBP1)’s Potential Function. Biologics 2025, 5, 14. https://doi.org/10.3390/biologics5020014
  • Vijayalingam S, Ezekiel UR, Xu F, Subramanian T, Geerling E, Hoelscher B, San K, Ganapathy A, Pemberton K, Tycksen E, Pinto AK, Brien JD, Beck DB, Chung WK, Gurnett CA and Chinnadurai G. Human iPSC-Derived Neuronal Cells from CTBP1-Mutated Patients Reveal Altered Expression of Neurodevelopmental Gene Networks. Frontiers in Neuroscience.2020;14:1-19. PMCID: PMC7653094
  • Beck DB, Subramanian T, Vijayalingam S, Ezekiel UR, Donkervoort S, Yang ML, Dubbs HA, Ortiz-Gonzalez XR, Lakhani S, Segal D, Au M, Graham JM Jr, Verma S, Waggoner D, Shinawi M, Bönnemann CG, Chung WK, Chinnadurai G. A pathogenic CtBP1 missense mutation causes altered cofactor binding and transcriptional activity. Neurogenetics. 2019; 20:129-43. PMCID: PMC8078134
  • Complete List of Published Work in MyBibliography: https://www.ncbi.nlm.nih.gov/sites/myncbi/18AwOwimlcMkp/bibliography/44578012/public/?sort=date&direction=ascending 

Professional Organizations and Associations

  • Society for Neuroscience
  • American Society for Microbiology
  • International Society for Stem Cell Research
  • American Society for Clinical Laboratory Science
  • American Association for Clinical Chemistry
  • American Society for Biochemistry and Molecular Biology