Ioannis Dragatsis, Ph.D.
Department of Physiology
Transgenic/Knockout Core, Center for Genomics & 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
- Ph.D. Institution: University of Athens, Greece
- Postdoctoral: Columbia University, College of Physicians and Surgeons, Department of Genetics and Development, New York, NY , USA
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.
- 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.
- Morini E, Dietrich P, Salani M, Downs HM, Wojtkiewicz GR, Alli S, Brenner A, Nilbratt M, LeClair JW, Oaklander AL, Slaugenhaupt SA, Dragatsis I. Sensory and autonomic deficits in a new humanized mouse model of familial dysautonomia. Hum Mol Genet. 2016 Mar 15;25(6):1116-28. doi: 10.1093/hmg/ddv634. Epub 2016 Jan 13. PubMed PMID: 26769677; PubMed Central PMCID: PMC4764193.
- Mir H, Meena AS, Chaudhry KK, Shukla PK, Gangwar R, Manda B, Padala MK, Shen L, Turner JR, Dietrich P, Dragatsis I, Rao R. Occludin deficiency promotes ethanol-induced disruption of colonic epithelial junctions, gut barrier dysfunction and liver damage in mice. Biochim Biophys Acta. 2016 Apr;1860(4):765-74. doi: 10.1016/j.bbagen.2015.12.013. Epub 2015 Dec 23. PubMed PMID: 26721332; PubMed Central PMCID: PMC4776745.
- Chaudhry KK, Samak G, Shukla PK, Mir H, Gangwar R, Manda B, Isse T, Kawamoto T, Salaspuro M, Kaihovaara P, Dietrich P, Dragatsis I, Nagy LE, Rao RK. ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice. Alcohol Clin Exp Res. 2015 Aug;39(8):1465-75. doi: 10.1111/acer.12777. Epub 2015 Jul 14. PubMed PMID: 26173414; PubMed Central PMCID: PMC4515212.
- Smeyne M, Sladen P, Jiao Y, Dragatsis I, Smeyne RJ. HIF1α is necessary for exercise-induced neuroprotection while HIF2α is needed for dopaminergic neuron survival in the substantia nigra pars compacta. Neuroscience. 2015 Jun 4;295:23-38. doi: 10.1016/j.neuroscience.2015.03.015. Epub 2015 Mar 19. PubMed PMID: 25796140; PubMed Central PMCID: PMC4524512.
- McKinstry SU, Karadeniz YB, Worthington AK, Hayrapetyan VY, Ozlu MI, Serafin-Molina K, Risher WC, Ustunkaya T, Dragatsis I, Zeitlin S, Yin HH, Eroglu C. Huntingtin is required for normal excitatory synapse development in cortical and striatal circuits. J Neurosci. 2014 Jul 9;34(28):9455-72. doi: 10.1523/JNEUROSCI.4699-13.2014. PubMed PMID: 25009276; PubMed Central PMCID: PMC4087216.
- Cheishvili D, Dietrich P, Maayan C, Even A, Weil M, Dragatsis I, Razin A. IKAP deficiency in an FD mouse model and in oligodendrocyte precursor cells results in downregulation of genes involved in oligodendrocyte differentiation and myelin formation. PLoS One. 2014 Apr 23;9(4):e94612. doi: 10.1371/journal.pone.0094612. eCollection 2014. PubMed PMID: 24760006; PubMed Central PMCID: PMC3997429.