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Ioannis Dragatsis, PhD

Professor
Department of Physiology

Director
Transgenic/Knockout Core, Center for Genomics and Bioinformatics

The University of Tennessee Health Science Center
894 Union Avenue
Memphis, TN 38163
Phone: 901.448.3615
Fax: 901.448.7126
Lab: 502 Nash Research Building
Email: Ioannis Dragatsis

Education

  • PhD Institution: University of Athens, Greece
  • Postdoctoral: Columbia University, College of Physicians and Surgeons, Department of Genetics and Development, New York, NY , USA

Research Interests

Project 1 Title: Analysis of a mouse model for Familial Dysautonomia

Familial Dysautonomia (FD) is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, leading to death before the age of 40. The disease is characterized by progressive degeneration of the sensory and autonomic nervous system. Despite the identification of the gene that causes FD (Ikbkap) and recent medical advances, no cure is available. We have generated a mouse model recapitulating the phenotypic features of the disease and our goal is to elucidate the mechanisms that lead to neuronal degeneration in FD and to test therapeutic strategies.

Project 2 Title: Analysis of the function(s) of huntingtin

Huntington's disease (HD) is an autosomal dominant disorder that affects 1 in 10,000 individuals. HD is characterized by chorea, rigidity and progressive dementia. Symptoms usually begin between the ages of 35 and 50 years, with death typically following 15 to 20 years later. HD is caused by the expansion of an unstable stretch of CAG triplet repeats within the coding region of the HD gene. Moreover the protein encoded by the HD gene, huntingtin, is a novel protein of unknown function.

We are using the mouse as a model organism. Inactivation of the mouse homologue of the HD gene results in embryonic lethality demonstrating that huntingtin is essential for early embryonic development. Conditional inactivation of the gene at later stages results in progressive neurodegeneration in the adult mouse, suggesting that huntingtin is also essential for neuronal survival.

Techniques Utilized:

  • Molecular Biology: DNA and RNA isolation, PCR, cloning, site-directed mutagenesis, sequencing, Southern and Northern analysis, RT-PCR analysis, RNase protection, in vitro transcription.
  • Biochemistry: SDS-Page, detection of proteins using immunoblotting and immunoprecipitation.
  • Cell Biology: Cell culture (mammalian cells and in particular fibroblasts and mouse embryonic stem cells (ES), transfection and electroporation of mammalian cells, immortalization of cell lines.
  • Histology: paraffin and frozen sectioning, immunohistochemistry, in-situ hybridisation, confocal microscopy. Skeleton preparation.
  • Mouse genetics: Generation of genetically engineered (transgenic, chimeric) mice. Embryo collection, microinjection and embryo transfer.

Representative Publications

  • Morini E, Gao D, Montgomery CM, Salani M, Mazzasette C, Krussig TA, Swain B, Dietrich P, Narasimhan J, Gabbeta V, Dakka A, Hedrick J, Zhao X, Weetall M, Naryshkin NA, Wojtkiewicz GG, Ko CP, Talkowski ME, Dragatsis I, Slaugenhaupt SA. ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia. Am J Hum Genet. 2019 Apr 4;104(4):638-650. doi: 10.1016/j.ajhg.2019.02.009. Epub 2019 Mar 21. PubMed PMID: 30905397; PubMed Central PMCID: PMC6451698.
  • Shukla PK, Meena AS, Manda B, Gomes-Solecki M, Dietrich P, Dragatsis I, Rao R. Lactobacillus plantarum prevents and mitigates alcohol-induced disruption of colonic epithelial tight junctions, endotoxemia, and liver damage by an EGF receptor-dependent mechanism. FASEB J. 2018 Jun 18:fj201800351R. doi: 10.1096/fj.201800351R. [Epub ahead of print] PubMed PMID: 29912589; PubMed Central PMCID: PMC6181630.
  • Dragatsis I, Dietrich P, Ren H, Deng YP, Del Mar N, Wang HB, Johnson IM, Jones KR, Reiner A. Effect of early embryonic deletion of huntingtin from pyramidal neurons on the development and long-term survival of neurons in cerebral cortex and striatum. Neurobiol Dis. 2018 Mar;111:102-117. doi: 10.1016/j.nbd.2017.12.015. Epub 2017 Dec 21. PubMed PMID: 29274742; PubMed Central PMCID: PMC5821111.
  • Dietrich P, Johnson IM, Alli S, Dragatsis I. Elimination of huntingtin in the adult mouse leads to progressive behavioral deficits, bilateral thalamic calcification, and altered brain iron homeostasis. PLoS Genet. 2017 Jul 17;13(7):e1006846. doi: 10.1371/journal.pgen.1006846. eCollection 2017 Jul. PubMed PMID: 28715425; PubMed Central PMCID: PMC5536499.
  • Xiao J, Vemula SR, Xue Y, Khan MM, Carlisle FA, Waite AJ, Blake DJ, Dragatsis I, Zhao Y, LeDoux MS. Role of major and brain-specific Sgce isoforms in the pathogenesis of myoclonus-dystonia syndrome. Neurobiol Dis. 2017 Feb;98:52-65. doi: 10.1016/j.nbd.2016.11.003. Epub 2016 Nov 24. PubMed PMID: 27890709; PubMed Central PMCID: PMC5283163.
  • Dietrich P, Dragatsis I. Familial Dysautonomia: Mechanisms and Models. Genet Mol Biol. 2016 Oct-Dec;39(4):497-514. doi: 10.1590/1678-4685-GMB-2015-0335. Epub 2016 Aug 4. PubMed PMID: 27561110; PubMed Central PMCID: PMC5127153.

View more references (pubmed link)

May 26, 2022