department of pharmacology

Jason Mears, Ph.D.

Mears

Assistant Professor

Phone: (216) 368-3348
Fax: 216-368-1300
E-mail: Jam348@case.edu
W147D

Summary of Research Interests

In multicellular organisms, mitochondria are involved in a range of cellular processes, including ATP production, Ca2+ homeostasis and regulation of programmed cell death (apoptosis). Fig2 Control of these diverse processes is directly related to the dynamic nature of mitochondria, which continually divide and fuse. Inhibition of the fission machinery leads to an elongated mitochondrial network within the cell. Conversely, inhibition of fusion results in small, fragmented organelles. Therefore, a delicate balance of fission and fusion is needed to prevent morphological changes that impair mitochondrial redistribution and function. Dr. Mears’s previous research has focused on Dnm1, the yeast DRP involved in mitochondrial fission. Using cryo-EM and image reconstruction techniques, he has examined the structure of Dnm1-lipid tubes and the molecular mechanism though which mitochondrial division occurs. Moving forward, his lab will pursue a detailed understanding of the molecular machinery associated with mitochondrial division in yeast and mammalian cells (Fig. 2) Using cryo-EM along with biochemical and computational techniques, Dr. Mears’s group will investigate the structure of the DRPs and factors that regulate its activity. Mitochondrial dynamics play a critical role in maintaining the health of eukaryotic cells, and defects in mitochondrial morphology are associated with an increasing number of human diseases, including cancer, neurodegeneration and aging. Future research in the Mears laboratory will pursue a detailed understanding of the relationship between mitochondrial dynamics and disease.

Selected Publications:

Joshua S. Chappie, Jason A. Mears, Shunming Fang, Marilyn Leonard, Sandra L. Schmid, Ronald A. Milligan, Jenny E. Hinshaw and Fred Dyda. (2011) Structural studies reveal an improved model for dynamin assembly. Manuscript in preparation.

Jason A. Mears, Laura Lackner, Shunming Fang, Elena Ingerman, Jodi Nunnari and Jenny E. Hinshaw. (2011) Conformational changes in Dnm1 support a contractile mechanism for mitochondrial fission. Nat. Struct. Mol. Biol., 18, 20-26.

Timothy A. Schulz, Mal-Gi Choi, Sumana Raychaudhuri, Jason A. Mears, Rodolfo Ghirlando, Jenny E. Hinshaw, and William A. Prinz (2009) Lipid-regulated sterol transfer between closely apposed membranes by oxysterol-binding protein homologs. J. Cell Biol., 187, 889-903.

Jason A. Mears and Jenny E. Hinshaw (2008) Visualization of dynamins. Methods in Cell Biol., 88, 237-256.

Jason A. Mears, Pampa Ray and Jenny E. Hinshaw (2007) A corkscrew model for dynamin constriction. Structure, 15, 1190-1202

Jason A. Mears*, Manjuli R. Sharma*, Robin R. Gutell, Amanda S. McCook, Paul E. Richardson, Thomas R. Caulfield, Rajendra K. Agrawal and Stephen C. Harvey (2006) A structural model of the large subunit of the mammalian mitochondrial ribosome. J. Mol. Biol., 358, 193-212.

Elena Ingerman, Edward M. Perkins, Michael Marino, Jason A. Mears, J. Michael McCaffery, Jenny E. Hinshaw and Jodi Nunnari (2005) Dnm1 forms spirals that are structurally tailored to fit mitochondria. J. Cell Biol., 170, 1021-1027.

Jason A. Mears, Scott M. Stagg, and Stephen C. Harvey (2005) Modeling large RNA assemblies using a reduced representation. In Handbook of RNA Biochemistry. Eds. Hartmann, R.K., Bindereif, A., Schon, A. and Westof, E. Wiley-VCH, Weinheim, Germany, pp. 546-559.

Valery I. Ivanov and Jason A. Mears (2004) Using crosslinks to study ribosomal dynamics. J. Biomol. Struct. Dyn., 21, 691-698.

Scott M. Stagg*, Jason A. Mears*, and Stephen C. Harvey (2003) A Structural Model for the Assembly of the 30S Subunit of the Ribosome. J. Mol. Biol., 328, 49-61

Jason A. Mears, Jamie J. Cannone, Scott M. Stagg, Robin R. Gutell, Rajendra K. Agrawal, and Stephen C. Harvey (2002) Modeling a minimal ribosome based on comparative sequence analysis. J. Mol. Biol., 321, 215-234.

*These authors contributed equally