Mercy Mascreen Davidson, M.Sc., Ph.D.
Senior Research Scientist
Columbia University College of Physicians and Surgeons
Area of expertise:
Genetics and biology of mitochondrial diseases
In vitro models of mitochondrial diseases
Microbeam irradiation induced mitochondrial damage
Blood-brain barrier in MELAS
Nuclear-mitochondrial genome interaction
Angiogenesis in MELAS
B.Sc., Biochemistry, 1968, Queen Mary’s College, Madras, India
M.Sc., Biochemistry, 1970, University of Madras, India
Ph.D., Biochemistry, 1979, University of Madras, India
Winsome F. Walker, M.P.H
Senior Research Worker
Huabin Huang, MD
Mitochondria contain their own DNA distinct from the nuclear DNA and precise interaction between the two genomes is necessary for normal function of the cell. Mitochondria play an important role not only in ATP synthesis, but also have important signaling and regulatory roles in cellular homeostasis. Dr. Davidson’s laboratory has been investigating the pathogenic mechanism of mitochondrial diseases and therapeutic strategies using complex in vitro disease models generated in her laboratory. These include cybrids (cytoplasmic hybrids) with a neutral nuclear background to study mtDNA mutations, transnuclear cell lines to test nuclear contribution in patients with homoplasmic mtDNA mutations. Dr. Davidson has generated a unique proliferating human ventricular cardiomyocyte cell line by a novel mitochondrial function-based approach, which can be used generically to force postmitotic cells to reenter the cell cycle.
Dr. Davidson’s group has demonstrated for the first time that mitochondria can interact resulting in functional complementation of non-overlapping deletions and point mutations in both proliferating cells as well as in postmitotic muscle. These data contribute to our understanding of mtDNA interactions and have implications in complementation of the effects of mtDNA mutations.
Currently, she is investigating genotoxic effects of environmental toxins and alpha particle radiation on mitochondrial dynamics and function to understand how these changes modulate bystander effects and genomic instability. Her current interests are in the study of the blood brain barrier (BBB) in MELAS using an in vitro model of the normal and MELAS BBB with the constituent cell types, to understand the pathogenesis of recurrent stroke-like episodes and cerebral edema in patients. This work has led her to evaluate angiogenesis as a compensatory mechanism of hypoxia in MELAS stroke patients. Another area of investigation is nuclear-mitochondrial genome interactions in the pathomechanism of mitochondrial cardiomyopthies. For this purpose, she has generated proliferating human cardiomyocyte cell lines from patient’s transplanted heart. Dr. Davidson’s research is currently funded by the National Institutes of Health (NIH), USA.
Commission on the status of women
Research Officers Committee
King, M. P., Koga, Y., Davidson, M. and Schon, E. A. Defects in mitochondrial protein synthesis and respiratory chain activity segregate with the tRNALeu(UUR) mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. Mol. Cell. Biol. (1992), 12, 480-490.
Papadapoulou L.C., Sue C.M., Davidson, M., Tanji, K, Nishino, Ichizo, Sadlock, JE, Krishna, S, Walker, W, Selby, J, Glerum, DM, Van Coster, R, Lyon, G, Scalais, e, labal, R, Kaplan, P, Shanske, S, De Vivo, D, Bonilla, E, Hirano, M, DiMauro, S and Schon, EA. Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nature Genetics: (1999), 3, 333-337.
Claudia Sobreira, Michael P.King, Mercy M. Davidson, Hyejong Park, Yasutoshi Koga and Armand, F. Miranda. Long-term analysis of differentiation in human myoblasts repopulated with mitochondria harboring mtDNA mutations. Biochem. Biophys. Res. Commun. (1999), 266, 179-186..
Leonardo Salviati, Evelyn Hernandez-Rosa, Winsome F. Walker, Sabrina Sacconi, Salvatore DiMauro. Eric A. Schon, and Mercy M. Davidson. Copper supplementation restores cytochrome c oxidase activity in cultured cells from patients with SCO2 mutations. Biochem. J. (2002), 363, 321-327.
Carla Giordano, Francesco Pallotti, Winsome F.Walker, Nicoletta Checcarelli, Olimpia Musumeci ,Filippo Santorelli, Giulia d’Amati, Eric A. Schon, Salvatore DiMauro, Michio Hirano, and Mercy M. Davidson. Pathogenesis of the deafness-associated A1555G mitochondrial DNA mutation. Biochim. Biophys. Res. Commun. (2002), 293, 521-529.
Robert W. Taylor, Carla Giordano, Mercy M. Davidson, Giulia d’Amati, Hugh Bain, Christine M. Hayes, Helen Leonard, Martin J. Barron, Carlo Casali, Filippo M. Santorelli, Michio Hirano, Robert N. Lightowlers, Salvatore DiMauro and Douglass M. Turnbull. A homoplasmic mitochondrial transfer ribonucleic acid mutation as a cause of maternally inherited hypertrophic cardiomyopathy. J. Amer. Coll. Cardiol. (2003), 41, 1786-1796..
F. Pallotti, A. Baracca, E. Hernandez-Rosa, W. F. Walker, G. Solaini, G. Lenaz, G.V. Melzi d’Eril, S. DiMauro, E.A. Schon, and M. Davidson. (2004). Biochemical analysis of respiratory function in cybrid cell lines harboring mtDNAmutations. Biochem J. (2004), 384, 287-294.
Mercy M. Davidson, Claudia Nesti, Winsome F. Walker, Evelyn Hernandez, Lev Protas, Michio Hirano and Nithila D. Isaac. Novel human cell lines derived from adult human ventricular cardiomyocytes. J. Mol. Cell. Cardiol. (2005), 39, 133-147
Michael A. Partridge, Sarah X.L. Huang, Evelyn Hernandez-Rosa, Mercy M. Davidson and Tom K. Hei. Arsenic induced mitochondrial DNA damage and altered mitochondrial oxidative function: Implications for genotoxic mechanisms in mammalian cells. Cancer Res. (2007) 67, 5239-5247.
Sabrina Sacconi, Leonardo Salviati, Yutaka Nishigaki, Winsome F. Walker, Evelyn Hernandez-Rosa, Eva Trevisson, Severine Delplace, Claude Desnuelle, Sara Shanske, Michio Hirano, Eric A. Schon, Eduardo Bonilla, Darryl C. De Vivo, Salvatore DiMauro, and Mercy M. Davidson. A functionally dominant mitochondrial DNA mutation. (2008), Hum. Mol. Genet. 17, 1814-1820.
Honging Zhou, Vladimir N. Ivanov, Yu-Chin Lien, Mercy Davidson and Tom K. Hei. Mitochondrial function and nuclear factor-kB-mediated signaling in radiation-induced bystander effects. (2008), Cancer Res., 68, 2233-2240.
Robert W. Gilkerson, Eric A. Schon, Evelyn Hernandez, and Mercy M. Davidson. Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation. (2008) J. Cell. Biol. 181, 1117-1128.
Mercy M. Davidson, Winsome F. Walker, Evelyn Hernandez-Rosa and Claudia Nesti. Evidence for nuclear modifier gene in mitochondrial cardiomyopathy. (2009) J, Mol, Cell, Cardiol. 46: 936-942.
Mercy M. Davidson, Winsome F. Walker and Evelyn Hernandez-Rosa. The m.3243A>G mtDNA mutation is pathogenic in an in vitro model of the human blood brain barrier. (2009). Mitochondrion, 9: 463-470.
M. D’Aurelio, C. Vives-Bauza, M.M. Davidson and G. Manfredi. Mitochondrial DNA background modifies the bioenergetics of NARP/MILS ATP6 mutant cells. Hum. Mol. Gen. (2010). 19: 374–386.
Huang SX, Partridge MA, Ghandhi SA, Davidson MM, Amundson SA, Hei TK. Mitochondria-derived reactive intermediate species mediate asbestos-induced genotoxicity and oxidative stress-responsive signaling pathways. (2012) Environ Health Perspect. 120, 840-847.
Casarin A, Giorgi G, Pertegato V, Siviero R, Cerqua C, Doimo M, Basso G, Sacconi S, Cassina M, Rizzuto R, Brosel S, Davidson MM, DiMauro S, Schon EA, Clementi M, Trevisson E, Salviati L.Copper and bezafibrate co-operate to rescue cytochrome c oxidase deficiency in cells of patients with SCO2 mutations.
Orphanet J Rare Dis. (2012) 7, 21.