My lab employs multi-dimensional Nuclear Magnetic Resonance (NMR) spectroscopy and other biophysical techniques to characterize the structures of proteins, and to probe the protein-drug and protein-protein interactions. The goal is to elucidate the mechanism of function of proteins associated with key cellular processes. By identifying a protein structure, we can understand how it functions and rationalize how specific mutations, or changes in amino acids, affect the overall function of the protein. We are currently focusing on three proteins in the lab: MID1, alpha4, and protein phosphatase 2A (PP2A). Loss of function of MID1 and alpha4 and increased concentration of PP2A result in errors in the development of specific regions along the midline region of the body. Abnormalities include cleft lip and palate, wide-spaced eyes, and defects in the brain, heart, and genitalia. We want to know the structures of MID1 and alpha4, understand how these two proteins interact, and determine how they regulate the concentration and function of PP2A. We use current state-of-the art biochemical techniques to make and purify proteins. A background in chemistry is all that is needed to successfully pursue this line of research. We are also initiating collaborations with faculty from other departments at GW and at nearby institutions to focus on other interesting proteins.
Tao H, Simmons BN, Singireddy S, Jakkidi M, Short KM, Cox TC, Massiah MA, Structure of the MID1 tandem B-boxes reveals an interaction reminiscent of intermolecular ring heterodimers, Biochemistry. 2008 Feb 26;47(8):2450-7. Epub 2008 Jan 26.
Han, X Du, H, Massiah, M.A. Detection and characterization of the in vitro e3 ligase activity of the human MID1 protein. J Mol Biol. 2011 Apr 8;407(4):505-20. Epub 2011 Feb 4.
Massiah MA, Matts JA, Short KM, Simmons BN, Singireddy S, Yi Z, Cox TC, Solution structure of the MID1 Bbox2 CHC(D/C)C(2)H(2) zinc-binding domain: insights into an evolutionarily conserved RING fold, J Mol Biol. 2007 May 25;369(1):1-10. Epub 2007 Mar 15.