Edward A. Dennis, Ph.D.
Chancellor’s I Distinguished Professor and Distinguished Professor of Pharmacology, Chemistry & Biochemistry, Emeritus
Edward Dennis, Ph.D.
Chancellor’s I Distinguished Professor and Distinguished Professor of Pharmacology, Chemistry & Biochemistry, Emeritus
Research Interests
The Dennis Laboratory has extended its LIPID MAPS initiative to quantitatively identify thousands of individual lipid molecular species in cells, blood and other tissues to advance our understanding of metabolic syndrome, cancer, infection, and various neurodegenerative diseases especially non-alcoholic fatty liver disease and NASH. It also hosts the UCSD LIPID MAPS Lipidomics Core.
The Dennis group also studies the structure and function of the phospholipase A2 enzyme superfamily. From these studies, they have developed a general model for the action of water-soluble enzymes acting at membrane phospholipid interfaces in which the membrane causes allosteric changes in the enzyme allowing it to bind a single phospholipid molecule in its catalytic site. The specificity of the each enzyme depends mainly on the specific fatty acid occupying the sn-2 position.
Since phospholipase A2 liberates free arachidonic acid from phospholipids, it plays a central role in the eicosanoid cascade and the initiation of inflammation, so the group is studying it’s in vivo specificity in macrophages and also focuses on developing potent pharmacological agents for controlling numerous diseases.
Selected Publications
Navratil AR, Shchepinov MS, Dennis EA (2018) Lipidomics reveals dramatic physiological kinetic isotope effects during the enzymatic oxygenation of polyunsaturated fatty acids ex vivo. J Am Chem Soc, 140, 235-43. [PMC5765537]
Mouchlis VD, Chen Y, McCammon JA, Dennis EA (2018) Membrane allostery and unique hydrophobic sites promote enzyme substrate specificity. J Am Chem Soc,140, 3285-91. [PMC5846079]
Gregus AM, Buczynski MW, Dumlao DS, Norris PC, Rai G, Simeonov A, Maloney DJ, Jadhav A, Xu Q, Wei SC, Fitzsimmons BL, Dennis EA, Yaksh TL (2018) Inhibition of spinal 15-LOX-1 attenuates TLR4-dependent, NSAID-unresponsive hyperalgesia in male rats. Pain, 159: 2620-9. [PMC6237621]
Mouchlis VD, Armando AM, Dennis EA (2019) Substrate specific inhibition constants for phospholipase A2 acting on unique phospholipid substrates in mixed micelles and membranes using lipidomics. J Med Chem, 62, 1999-2007. [PMC6398150]
Watrous JD, Niiranen TJ, Lagerborg KA, Henglin M, Xu YJ, Rong J, Sharma S, Vasan RS, Larson MG, Armando AM, Mora S, Quehenberger O, Dennis EA, Cheng S, Jain M (2019) Directed non-targeted mass spectrometry and chemical networking for discovery of eicosanoids and related oxylipins. Cell Chem Biol, 26, 433-42. [PMC6636917]
Venn-Watson S, Lumpkin R, Dennis EA (2020) Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? Sci Rep, 10, 8161. [PMC7235264]
Tam VC, Suen R, Treuting PM, Armando A, Lucarelli R, Gorriochotegui-Escalante N, Diercks A, Quehenberger O, Dennis EA, Aderem A, Gold ES (2020) PPARα exacerbates necroptosis leading to increased mortality in post-influenza bacterial super-infection. Proc Natl Acad Sci USA, 117, 15789-98. [PMC7355019]
Hayashi D, Mouchlis VD, Dennis EA (2021) Omega-3 versus omega-6 fatty acid availability is controlled by hydrophobic site geometries of phospholipase A2s, J Lipid Res, 62, 100113, https://doi.org/10.1016/j.jlr.2021.100113. [PMC8551542]
Mouchlis VD, Hayashi D, Vasquez AM, Cao J, McCammon JA, Dennis EA (2022) Lipoprotein-associated phospholipase A2: a paradigm for allosteric regulation by membranes, Proc Natl Acad Sci USA 119, e2102953118. [PMC8764669]
Mouchlis VD, Dennis EA (2022) Membrane association allosterically regulates phospholipase A2 enzymes and their specificity. Acc Chem Res, 55, 3303-11. https://pubs.acs.org/doi/10.1021/acs.accounts.2c00497. [PMC9730854]