25% Biology, 75% Chemistry
B.A. Biochemistry, 2004 University of Texas at Austin; Ph.D., 2009 University of Texas at Austin; Postdoctoral Fellow 2009-2014, University of Michigan
- ASPET Molecular Pharmacology Division Young Scientist Award, 2012
- American Heart Association Post-Doctoral Fellow, 2011-2014
- Lyon, A.M., Begley, J.A., Manett, T.D., and Tesmer, J.J.G., Molecular Mechanisms of PLCβ3 Autoinhibition, Structure 2014, 22, , 1844-1854 ,
- Lyon, A.M., Dutta, S., Boguth, C.A., Skiniotis, G., and Tesmer, J.J.G., Structure of Full-Length Phospholipase C β3 in Complex with Gαq Reveals Functional Interfaces of its Cterminal Coiled-Coil Domain, Nat. Struct. Mol. Biol. 2013, 20, , 355-362 ,
- Lyon, A.M., Tesmer, V.M., Dhamsania, V. D., Thal, D.M., Gutierrez, J., Chowdhury, S., Suddala, K., Northup, J.K., and Tesmer, J.J.G., An Autoinhibitory Helix in the C-Terminal Region of Phospholipase Cβ Represses Basal Activity and Mediates Gαq Activation, Nat. Struct. Mol. Biol. 2011, 18, , 999-1005 ,
Professional Faculty Research
Cardiovascular disease is a growing problem worldwide and the leading cause of death in the United States. Phospholipase C (PLC) enzymes, in particular PLCβ and PLCε, are essential for normal cardiovascular function. These proteins generate second messengers that regulate the concentration of intracellular calcium and the activation of protein kinase C (PKC). Dysregulation of calcium levels and PKC activity can result in cardiovascular diseases and heart failure. PLCβ is regulated principally via interactions with the heterotrimeric G protein subunits Gαq and Gβγ. Much less is known about the regulation and activation of PLCε. PLCε integrates and amplifies signals generated by tyrosine kinase receptors and G protein-coupled receptors via small GTPases such as Ras, Rho, and Rap.
My lab uses an innovative combination of X-ray crystallography and cryo-electron microscopy to gain structural insights into PLC regulation and activation. Structure-based hypotheses are validated through functional assays, and ultimately cell-based and whole animal studies. A long-term interest is the development of small molecule modulators to regulate PLCε function. These studies will aid in the identification and development of novel chemical probes that could be used to study and potentially treat cardiovascular disease.