Department of Cellular and Structural Biology
CSB Postdoctoral Fellow
Sharma, Lokendra Select a Tab
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- I joined the Department of Cellular and Structural Biology in Dr. Yidong Bai's lab in September 2007 as a postdoctoral fellow. My area of research is to investigate the role of mitochondrial dysfunctions caused by pathogenic mitochondrial DNA mutations in human diseases.
- Mammalian mitochondrial genome is a double-stranded circular DNA of nearly 16 kb and contains 37 genes encoding 13 peptides for the respiratory chain as well as 22 tRNAs and 2 rRNAs essential for protein synthesis within mitochondria. Since mtDNA is in the proximity of reactive oxygen species (ROS) generation sites (respiratory chain) and has relatively less sophisticated DNA protection or repair systems, mtDNA is therefore vulnerable to high mutation rates. High levels of mtDNA mutations have been found in many tumors and cancer cells. Also, accumulation of mtDNA mutations has been suggested to play a major role in the aging and development of neurodegenerative diseases. Still it is a question of debate, whether these mutations are the causes or consequences of such diseases. How mtDNA mutations contribute in the development of disease phenotype. Due to the multiplicity of mitochondrial genomes in each cell, a threshold of mutant mtDNA must be reached before cellular dysfunction caused by defective mitochondria becomes apparent. Isolated deficiency of respiratory complex I is the most frequent among mitochondrial disorders, which has been linked to the mutations in genes encoding complex I subunits and assembly factors. Also it is a site of production of ROS, which also mediates cellular functions ranging from apoptosis and necrosis to cell proliferation and carcinogenesis.
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My research interest includes:
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1. Investigate the regulatory mechanisms within mitochondria and the role of mitochondria in regulating various cellular pathways.
2. In particular, to study the cellular mechanism or effect of pathogenic mtDNA mutations in respiratory complex I. These mutations are associated with human diseases including cancer and aging.
3. Develop approaches to restore the mitochondrial functions in cells with mitochondrial deficiency.
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Lu J, Sharma LK, Bai Y. (2009)
Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res. 2009 Jul;19(7):802-15. -
Sharma LK*, Lu J, Bai Y. (2009)
Mitochondrial respiratory complex I: structure, function and implication in human diseases. Curr Med Chem. 2009;16(10):1266-77. -
Park JS, Sharma LK*, Li H, Xiang R, Holstein D, Wu J, Lechleiter J, Naylor SL, Deng JJ, Lu J, Bai Y. (2009)
A heteroplasmic, not homoplasmic, mitochondrial DNA mutation promotes tumorigenesis via alteration in reactive oxygen species generation and apoptosis.
Hum Mol Genet. 2009 May 1;18(9):1578-89. - Madina BR, Sharma LK, Chaturvedi P, Sangwan RS, Tuli R. (2007) Purification and characterization of a novel glucosyltransferase specific to 27beta-hydroxy steroidal lactones from Withania somnifera and its role in stress responses. Biochim Biophys Acta. 2007 Sep;1774(9):1199-207.
- Sharma LK, Madina BR, Chaturvedi P, Sangwan RS, Tuli R. (2007) Molecular cloning and characterization of one member of 3beta-hydroxy sterol glucosyltransferase gene family in Withania somnifera. Arch Biochem Biophys. 2007 Apr 1;460(1):48-55.