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My laboratory is interested in determining mechanisms that control organelle organization and trafficking in neurons and cause(s) of neurological disorders. For example, mitochondria integrate their apparently dissimilar functions (energy metabolism, motility and programmed cell death), and synergistically respond to exogenous perturbations. This mitochondrial synergy with their functions is vital along the long neuronal processes, where mitochondria are critically positioned. By using cellular, biochemical, molecular biology techniques and state-of-the art microscopy, we are studying how alcohol-induced oxidative stress alters mitochondrial dynamics. Alcohol is simply used as a model system, given the clear link between alcohol and oxidative stress. The temporal movement and spatial distribution of mitochondria in cells has the potential to develop into a tool to differentiate between healthy and diseased cells.
Related projects in the laboratory are focused on elucidating the role of mitochondrial fusion, fission and biogenesis and antioxidant status in neuro-degeneration. Mitochondrial biogenesis is under the direct control of a transcription factor, PGC1-α. We are studying the regulation of PGC1-α under conditions of oxidative stress and if these mechanism(s) are reversible.
- Das K, De la Garza G, Maffi S, Saikolappan S, and Dhandayuthapani S: (2012). Methionine sulfoxide reductase A (MsrA) deficient Mycoplasma genitalium shows decreased interactions with host cells. PLoS One. 7(4): e36247.
- Cheng B, Maffi SK, Martinez AA, Acosta YP, Morales LD, and Roberts JL: (2011). Insulin-like growth factor-I mediates neuroprotection in proteasome inhibition-induced cytotoxicity in SH-SY5Y cells. Mol Cell Neurosci. 47(3): 181-90.
- Maffi SK, Rathinam ML, Cherian PP, Pate W, Hamby-Mason R, Schenker S, and Henderson GI: (2008). Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol-induced apoptosis. J Neurosci Res. 86(5): 1064-76.
- Quinones MP, Kalkonde Y, Estrada CA, Jimenez F, Ramirez R, Mahimainathan L, Mummidi S, Choudhury GG, Martinez H, Adams L, Mack M, Reddick RL, Maffi S, Haralambous S, Probert L, Ahuja SK, and Ahuja SS: (2008). Role of astrocytes and chemokine systems in acute TNFα induced demyelinating syndrome: CCR2-dependent signals promote astrocyte activation and survival via NF-KB and Akt. Mol Cell Neurosci. 37(1): 96-109.
- Kalkonde YV, Morgan WW, Sigala J, Maffi SK, Condello C, Kuziel W, Ahuja SS, and Ahuja SK: (2007). Chemokines in the MPTP model of Parkinson's disease: absence of CCL2 and its receptor CCR2 does not protect against striatal neurodegeneration. Brain Res. 1128(1): 1-11.
- Sanyal SN, Goyal M, Kanwar SS, and Kaushal S: (2006). Use of phospholipid transfer protein as a probe to study the lipid dynamics and alkaline phosphatase activity in the brush border membrane of human term placenta. Chem Biodivers. 3(5): 527-34.
- Zeng XC, Bhasin S, Wu X, Lee JG, Maffi S, Nichols CJ, Lee KJ, Taylor JP, Greene LE, and Eisenberg E: (2004). Hsp70 dynamics in vivo: effect of heat shock and protein aggregation. J Cell Sci. 117(Pt 21): 4991-5000.
- Ramachandran V, Watts LT, Maffi SK Chen J, Schenker S, and Henderson G: (2003). Ethanol-induced oxidative stress precedes mitochondrially mediated apoptotic death of cultured fetal cortical neurons. J Neurosci Res. 74(4): 577-88.
- Ma Y, Greener T, Pacold ME, Kaushal S, Greene LE, and Eisenberg E: (2002). Identification of domain required for catalytic activity of auxilin in supporting clathrin uncoating by Hsc70. J Biol Chem. 277(51): 49267–74.
- Kaushal S, Ghosh S, Sharma N, Sanyal SN, and Majumdar S: (2001). Role of phospholipid transfer protein in rabbit lung development. Cell Mol Life Sci. 58(14): 2098-107.
- Wu X, Zhao X, Baylor L, Kaushal S, Eisenberg E, and Greene LE: (2001). Clathrin exchange during clathrin-mediated endocytosis. J Cell Biol. 155(2): 291-300.
- Karthikeyan G, Narang A, Majumdar S, and Shivani K: (1997). Photooxidant injury to glucose-6-phosphate dehydrogenase-deficient erythrocytes with bilirubin as the sensitizer--an in vitro study. Acta Paediatr. 86(3): 321-2.
- Gupta A, Kaushal S, Majumdar S, and Sanyal SN: (1996). Isolation of type II epithelial cells from rabbit fetal lungs by adherence on an IgG-coated surface. Experientia. 52(8): 799-802.
- Gupta A, Juneja R, Kaushal S, Majumdar S, and Sanyal SN: (1995). Effect of Ca(2+)-channel blockers, Ca(2+)-ionophore and increased pyrene excimer formation on the microsomal glucose-6-phosphatase. Indian J Biochem Biophys.32(5): 272-8.
- Nehru B and Kaushal S: (1993). Alterations in the hepatic enzymes following experimental lead poisoning. Biol Trace Elem Res. 38(1): 27-34.
- Nehru B and Kaushal S: (1992) Effect of lead on hepatic microsomal enzyme activity. J Appl Toxicol. 12(6): 401-5.
- Nehru B and Kaushal S: (1991) Biochemical and histological alterations following experimental lead poisoning. J Trace Elem Exp Med. 4: 203-9.