Our research activities in relate to the elucidation of molecular mechanisms underlying signal transduction and gene regulation pathways that are of central importance in human vascular biology and disease pathology. Our goal is to elucidate the conformations, interacting surfaces, and binding selectivities of proteins at the atomic level to reveal those molecular details of structure/function that can be incorporated into the development of novel therapeutics for human disease. We use a combination of molecular biological, biochemical, and biophysical techniques to delineate these mechanisms at the atomic level. In particular, we use heteronuclear multi-dimensional nuclear magnetic resonance (NMR) spectroscopy to determine the three-dimensional structures of proteins that play critical roles in the development of human diseases, including cardiovascular disease, cancer, sepsis, and inherited renal diseases.
Our activities have expanded to the application of computational biology and bioinformatics to investigate proteins, peptides, and nucleic acids for their structure/function relationships. This aspect of our work concerns the molecular modeling of proteins and peptides, the in silico dynamic simulation of molecular interactions between proteins or between proteins and DNA, molecular assessment of the structural consequence of amino acid mutation, and the development of computational tools to further elucidate structure/function mechanisms from protein structure database information.
Grant, MA, Baron, RM, Macias, AV, Perrella, MA, Rigby, AC. Netropsin improves survival from endotoxemia by disrupting HMGA1-binding to the NOS2 promoter, Biochem J, 2009, 418:103-112.
Grant, MA. Protein structure prediction in structure-based ligand design and virtual screening. Combinatorial Chemistry and High Throughput Screening, 2009, in press.
Grant, MA, Lazo, ND, Lomakin A, Condron, MM, Arai, H, Yamin, G, Rigby, AC, Teplow, DB. Familial Alzheimer’s Disease Mutations Alter the Stability of the Amyloid-beta Protein Monomer Folding Nucleus, Proc. Natl. Acad. Sci USA, 2007, 104(42):16522-7.
Grant, MA, Kalluri, R. The Structural Basis for the Functions of Endogenous Angiogenesis Inhibitors. Cold Spring Harb Symp Quant Biol, 2006, 70:399-410.
Grant, MA, Baikeev, R, Gilbert, GE, Rigby, AC. Lysine 5 and Phenylalanine 9 of the Factor IX w-loop interact with phosphatidylserine in a membrane mimetic environment. Biochemistry, 2004, 43(49): 15367-78.
External Recognition:
Predoctoral Research Scholarship Award, PhRMA Foundation, 2001-2003.
Individual NRSA Fellowship Award, National Heart, Lung, and Blood Institutes, NIH, 2001-2003.
Young Investigator Award, International Society for Thrombosis and Haemostasis, International Meeting, 2003.
Scientist Development Grant, American Heart Association, National Affiliate, 2005-08.
