Richard W. Gross, M.D., Ph.D.

Professor
Internal Medicine
Bioorganic Chemistry
Developmental Biology
Chemistry

Molecular Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-2690

  • 314-362-2228

  • 314-362-2229

  • 314-362-1402

  • 8020

  • East Building, Room 101, Basement

  • rgross@wustl.edu

  • phospholipase A2, diabetes, obesity, receptor, myocardial ischemia, lipid metabolism

  • The molecular mechanisms through which biologic membranes participate in cellular activation processes

Research Abstract:

Our research is focused on the molecular mechanisms through which biologic membranes participate in cellular activation. We study both the regulation of reactions which generate lipid second messengers from membrane phospholipids (e.g. phospholipases) as well as the effects of alterations in membrane organization, membrane-protein interactions and membrane dynamics on these processes. Our research examines membrane function in health and membrane dysfunction in three disease states including: 1) Myocardial ischemia where activation of intracellular phospholipases compromise ion channel function and precipitate sudden death; 2) Obesity where we have discovered a family of new lipases which regulate energy storage and utilization in fat and muscle; and 3) Diabetes where we have uncovered new mechanisms of insulin resistance, receptor signaling and key alterations in lipid metabolism. To facilitate progress in these areas, we are advancing new technologies (e.g., mass spectrometric techniques in lipidomics, metabolomics, and proteomics) to define the precise chemical interactions which underlie these disease processes. Through the use of basic chemical principles we are extending the frontiers of these technologies to impact on the major medical problems of the 21st century.

Selected Publications:

Yang K, Jenkins CM, Dilthey B, Gross RW. (2015) Multidimensional mass spectrometry-based shotgun lipidomics analysis of vinyl ether diglycerides. Anal. Bioanal. Chem. 407:5199-5210. PMCID: PMC4474766.

Kiebish, M.A., Yang, K., Liu, X., Mancuso, D.J., Zhao, Z., Sims, H.F., Cerqua, R., Cade, W.T., Han, X., and Gross, R.W. (2013) Dysfunctional Cardiac Mitochondrial Bioenergetic, Lipidomic, and Signaling in a Murine Model of Barth Syndrome. J. Lipid Res. 54:1312-1325. PMCID: PMC3622326.

Moon SH, Jenkins CM, Liu X, Guan S, Mancuso DJ and Gross RW. (2012) Activation of mitochondrial calcium-independent phospholipase A2gamma (iPLA2gamma) by divalent cations mediating arachidonate release and the production of downstream eicosanoids. J. Biol. Chem. 287:14880-14895. PMCID: PMC3340231

Moon SH, Jenkins CM, Kiebish MA, Sims HF, Mancuso DJ, and Gross RW. (2012) Genetic ablation of calcium-independent phospholipasesA2gamma (iPLA2gamma) attenuates calcium-induced opening of the mitochondrial permeability transition pore and resultant cytochrome C release. J. Biol. Chem. 287:29837-29850. PMCID: PMC3436185.

Gross RW and Han X. (2011) Lipidomics at the interface of structure and function in systems biology.
Chem. Biol. 18:284-291. PMCID:PMC21439472.

Jenkins CM, Yang J, Sims HF and Gross RW. (2011) Reversible high affinity inhibition of phosphofructokinase-1 by acyl-CoA: A mechanism integrating glycolytic flux with lipid metabolism. J. Biol. Chem. 286:11937-11950. PMCID:PMC3069396.

Mancuso DJ, Sims HF, Yang K, Kiebish MA, Su X, Jenkins CM, Guan S, Moon SH, Pietka T, Nassir F, Schappe T, Moore K, Han X, Abumrad NA and Gross RW. (2010) Genetic ablation of calcium-independent phospholipase A2γ prevents obesity and insulin resistance during high fat feeding by mitochondrial uncoupling and increased adipocyte fatty acid oxidation. J. Biol. Chem. 285:36495-36510. PMCID:PMC2978578.

Mancuso DJ, Kotzbauer P, Wozniak DF, Sims HF, Jenkins CM, Guan S, Han X, Yang K, Sun G, Malik I, Conyers S, Green KG, Schmidt RE and Gross RW. (2009) Genetic ablation of calcium-independent phospholipase A2gamma leads to alterations in hippocampal cardiolipin content and molecular species distribution, mitochondrial degeneration, autophagy and cognitive dysfunction. J Biol Chem 284:35632-35644. PMCID:PMC2790994.

Moon SH, Jenkins CM, Mancusco DJ, Turk J, and Gross RW. (2008) Smooth muscle cell arachidonic acid release, migration, and proliferation are markedly attenuated in mice null for calcium-independent phospholipase A2beta. J. Biol. Chem. 283:33975-33987. PMCID:PMC2590683.

Sun G, Yang K, Zhao Z, Guan S, Han X and Gross RW. (2008) Matrix-assisted mass spectrometric analysis of cellular glycerophospholipids enabled by multiplexed solvent dependent analyte-matrix interactions. Anal. Chem. 80:7576-7585. PMCID:PMC2963173.

Mancuso DJ, Sims HF, Han X, Jenkins CM, Guan SP, Yang K, Moon SH, Pietka T, Abumrad NA, Schlesinger PH and Gross RW. (2007) Genetic ablation of calcium-independent phospholipase A2γ leads to alterations in Mitochondrial lipid metabolism and function resulting in a deficient mitochondrial bioenergetic phenotype. J. Biol. Chem. 282:34611-34622. PMCID:PMC2980283.

Last Updated: 8/18/2015 8:46:35 AM

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