mlesort@uab.edu
Education:
- 1987 Baccalaureat, Mathematics and Natural Sciences, Universite des Sciences et Techniques, Nantes, France
- 1991 BS, Cellular Biology and Physiology, Universite des Sciences et Techniques, Nantes, France
- 1992 M.S., Cellular Biology and Physiology, Universite des Sciences et Techniques, Nantes, France
- 1993 Advanced Degree in Neuronal Science, Universite Pierre & Marie Curie, Paris, France
- 1997 Ph.D., Neurobiology, Universite Pierre & Marie Curie, Paris, France
- 1997-2000 Postdoctoral Fellow, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham
- 2000-2001 Research Assistant Professor, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham
Academic Appointments with UAB:
- 2001-present Assistant Professor Department of Psychiatry (primary appointment)
- 2001-present Assistant Professor, Department of Pharmacology and Toxicology, UAB (secondary appointment)
- 2001-present Member of The Vision Science and Neuroscience Graduate Programs, UAB
- 2002-present Assistant Professor, Department of Cell Biology, UAB (secondary appointment).
- 2004-present Associate Scientist, Minority Health & Research Center, UAB.
Research Interests:
- Pathogenesis of Huntington’s Disease
The research interest of our laboratory is directed toward understanding the pathogenesis of Huntington’s disease. Huntington’s disease is a devastating inherited neurodegenerative disorder initiated by a pathological expansion of a glutamine domain within the huntingtin protein. Currently there is no effective treatment to slow the progression or to delay the onset of HD, and sadly, the disease is invariably lethal. The development of Huntington’s disease mouse and cellular models has provided important insights regarding the molecular mechanisms contributing to Huntington’s disease pathology. The primary focus of our research program is to understand the specific mechanisms by which the mutant huntingtin initiates Huntington’s disease pathogenesis in order to propose therapeutic strategies that will delay the onset or slow the progression of the disease. Previously we have demonstrated that the mutant huntingtin protein is associated with the outer mitochondrial membrane and directly facilitates the calcium-induced mitochondrial permeability transition pore opening (Choo et al. 2004). Currently our laboratory is (i) examining the mechanisms by which the mutated huntingtin protein compromises mitochondrial functions, (ii) taking advantages of genetically modified mice to determine if increasing the mitochondrial calcium buffering capacity can prevent or attenuate the neuropathological and behavioral phenotypes of various Huntington’s disease mouse models. The results of these studies will provide important information determining if targeting mitochondria calcium buffering defects constitute a valid therapeutic target in Huntington’s disease.
Recent Publications:
Lesort M., Lee M., Tucholski J., Johnson G.V.W. 2003 Cystamine inhibits caspase activity: implication for polyglutamine disorders. The Journal of Biochemistry. Vol278(6):3825-3830.
Ruan, Q., Lesort, M., MacDonald, M. E., and Johnson, G. V., 2004, Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway, Human Molecular Genetic 13(7):669-681.
Choo Y., Johnson G. V., MacDonald M., Detloff P. J., and Lesort M., 2004, Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Human Molecular Genetic 13(14):1407-20.
Hunter J.M., Crouse A.B., Lesort M., Johnson G.V.W., Detloff. P.J. 2005. Verification of Somatic CAG Repeat Expansion by Pre-PCR Fractionation. Journal of Neuroscience Methods, May 15;144(1):11-7.
Choo YS, Mao Z, Johnson GV, Lesort M. 2005. Increased glutathione levels in cortical and striatal mitochondria of the R6/2 Huntington's disease mouse model. Neuroscience Letters. Sep 23;386(1):63-8.
Seong IS, Ivanova E, Lee JM, Choo YS, Fossale E, Anderson M, Gusella JF, Laramie JM, Myers RH, Lesort M, Macdonald ME. 2005. HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Human Molecular Genetics. Oct 1;14(19):2871-80.
Mao Z., Choo Y.S., Lesort M. Cystamine and Cysteamine Prevent the 3-NP-Induced Mitochondrial Depolarization of Huntington’s Disease Knock-in Striatal Cells. 2006. European Journal of Neuroscience 23 (7), 1701-1710.