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Daniel Raben Portrait

Daniel Raben
Professor of Biological Chemistry
Johns Hopkins University School of Medicine

725 N. Wolfe St.
Hunterian 502
Baltimore, MD21205
Office Phone: 410-955-1289
Lab Phone: 410-955-1410
Fax: 410-955-5759
Email: draben@jhmi.edu
Lab Web Site

Click Here for PDF of CV

Biochemistry and chemistry of lipids and lipid metabolizing enzymes involved in signaling cascades

Lipid second messengers have emerged as major components in a number of signaling cascades. The importance of these pathways is underscored by the observations demonstrating that defects in these pathways often contribute to pathological conditions such as diabetes, cardiovascular diseases, neurological disorders, dysfunctions of the immune system, and cancer among others. Understanding the regulation of the enzymes involved in controlling these lipid-involved pathways, therefore, will provide key insights into novel therapeutic targets.

A major effort in our laboratory is focused on understanding the biochemistry and chemistry underlying the molecular aspects involved in regulating lipid metabolizing signaling enzymes and the physiological roles of this regulation. Control of lipid metabolizing enzymes involves the modulation of two key parameters; their sub-cellular distribution and their intrinsic enzymatic activity. Our studies have concentrated on three families of lipid-metabolizing signaling enzymes, diacylglycerol kinases, phospholipases C, and phospholipases D. In addition to these enzymes, we are also interested in enzymes involved in sphingolipid metabolism as these lipids also play important roles in signaling cascades. Specific areas of interest are listed below.
 
Enzymology of Lipid Metabolizing Signaling Enzymes: A major effort in our laboratory is centered on investigating the effects of agonist stimulation on the intrinsic activities of these enzymes. We are particularly interested in identifying the critical modulating proteins, lipids, and post-translational modifications. In these studies we consider the fact that these enzymes, like most lipid metabolizing enzymes, are interfacial enzymes and their regulation potentially includes a number of interfacial-dependent parameters. Interestingly, our recent studies show that some of the interfacial parameters are indeed altered upon agonist stimulation.
 
Enzyme Structure/Function Studies: We are also interested in the structural components of these enzymes that are critical for their distribution/re-distribution to specific sub-cellular compartments. Additionally, and to compliment the enzymology studies, we are interested in elucidating the catalytic mechanism(s) of these enzymes. These studies will be conducted partly in collaboration with Dr. Albert Mildvan. Our long-term goal is to understand the biochemistry and chemistry of these enzymes and determine how changes in their sub-cellular localization and/or enzymatic activity affect their signaling functions.
 
Nuclear Signaling Cascades: In the course of our studies we have shown that some of the lipid-metabolizing signaling enzymes redistribute to unique sub-cellular compartments including the nucleus in response to particular agonists in various cell types. In that, one of our major goals is to understand the biochemistry and physiological roles of novel agonist-induced signaling cascades that involve lipid metabolism at the nucleus. Evidence is increasing that implicates these pathways in a number of important signaling systems including, but not limited to, those that regulate growth, differentiation, mRNA export, and chromatin remodeling.
Recent Publications

Tu-Sekine, B. and Raben, D.M. (2011) Regulation and roles of neuronal diacylglycerol kinases: a lipid perspective. Crit. Rev. Biochem. Mol. Biol. May 4 (Epub ahead of print).
PubMed Reference 

Link, T.M., Park, U., Vonakis, B.M., Raben, D.M., Soloski M.J., Caterina, M.J. (2010) TRPV2 plays a pivotal role in macrophage particle binding and phagocytosis. Nature Immunology Mar;11(3):232-9. Epub 2010 Jan 31.
PubMed Reference

Tu-Sekine, B. and Raben, D.M. (2010) Characterization of Cellular DGK-. Advances in Enzyme Reg. 50:81-94.
PubMed Reference

Raben, D.M. and Wattenberg, B.W. (2009) Signaling at the Membrane Interface by the DGK/SK Enzyme Family. J Lipid Res 50th Anniversary Edition: J. Lipid Res. April Supplement: S35-S39.
PubMed Reference

Tu-Sekine and Raben D.M. (2009) Regulation of DGK- J. Cell Physiol. 220(3):548-52.
PubMed Reference

Tu-Sekine, B., Ostroski, M, and Raben, D.M. (2007) Modulation of DGKq Activity by a-Thrombin and Phospholipids. Biochemistry, 46(3): 924 -932.
PubMed Reference

Wattenberg, B.W. and Raben, D.M. (2007) Diacylglycerol Kinases Put the Brakes on Immune Function. Science STKE (398) pe43.
PubMed Reference

Raben, D.M. and Tu-Sekine (2007) Nuclear Localization Of Diacylglycerol Kinases: Regulation And Roles. Frontiers in Bioscience 13:590-597.
PubMed Reference

Tu-Sekine, B., Ostroski, M. and Raben, D.M. (2006) Analysis of Two Diacylglycerol Kinase Activities in Mixed Micelles. Advances in Enzyme Regulation.
Pub Med Reference

Wattenberg, BW, Piston, SM, and Raben, D.M. (2006) The Sphingosine- and Diacylglycerol-Kinase Superfamily of Signaling Kinases. Localization as a key to signaling function. J Lipid Res. 47(6):1128-1139.
Pub Med Reference

Raben, DM. (2006) Lipid Signaling in the Nucleus. Biochem Biophys Acta 1761(5-6):503-4.
PubMed Reference​

Raben DM, Baldassare JJ. (2005) A new lipase in regulating lipid mobilization: hormone-sensitive lipase is not alone. Trends Endocrinol Metab. Mar;16(2):35-6.
PubMed Reference

Ostroski M, Tu-Sekine B, Raben DM. (2005) Analysis of a novel diacylglycerol kinase from Dictyostelium discoideum: DGKA. Biochemistry. Aug 2;44(30):10199-207.
PubMed Reference​

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