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   Jon Lomasney, MD
   Associate Professor of Pathology
   Associate Professor of Molecular Pharmacology and Biochemistry
   Director of Autopsy      
   Ward 3-210
   303 E. Chicago Avenue  
   Chicago, IL  60611

   j-lomasney@northwestern.edu
   http://www-lomasney.pathology.northwestern.edu/

Phone:  (312) 503-0450    

Anatomic Pathology Division
Autopsy  

Medical School

Dartmouth Medical School

Site of Residency

Duke University Medical Center

Site of Fellowship

Duke University Medical Center

Research Interests

Lipids are important regulators of the activity of many proteins including those involved in cardiac, vascular, pulmonary, and neural regulation, yet little is known about the molecular mechanisms mediating these effects. My laboratory staff members are engaged in a program of basic research to elucidate the molecular mechanisms by which lipids act as specific ligands to regulate cellular responses, and to investigate in select areas of cardiovascular disease how aberrations of signaling pathways may play a vital role in the pathogenesis of human disease.

We have used the family of phosphoinositide-specific phospholipase C isoforms as a model to study protein-lipid interactions. Upon stimulation by various hormones these membrane associated enzymes hydrolyze polyphosphoinositides to yield second messengers such diacylglycerol and inositol 1,4,5-trisphosphate. The determinants of enzyme function are complex and can be broken down into several primary components: substrate binding and catalysis, enzyme translocation, and regulation. During the past several years we have identified the structural motifs in the PLC delta 1 isoform that mediate each of the three primary functions. All three motifs require the binding of a specific lipid for function. The structural motif mediating translocation also modulates the rate catalysis, and is encoded by a unique domain termed the pleckstrin homology or PH domain. This newly discovered protein module of 100 amino acids exists in many molecules (including PLC d1) that participate in signal transduction. Our research is among the first to demonstrate a clear function in signal transduction for the PH domain, and serves a paradigm for the activation and regulation of many signaling molecules.

Work in progress includes characterization of a new family of PLC isoforms and the elucidation of the physiological roles of various PLC isoforms using primary cell culture and transgenic mice.

Techniques

Our laboratory is not technique-driven. We utilize many different techniques in our work depending on the questions we are addressing including those from cell biology, protein biochemistry, molecular biology, pharmacology, and genetics. The following methods are employed in the laboratory: radionuclide ligand binding and analysis, high performance stearic-exclusion liquid chromatography, cell culture, affinity chromatography, photoaffinity labeling, SDS-gel electrophoresis, protein assay, Western blotting, DNA/RNA isolation and characterization by Northern and Southern blotting, isolation of novel genes and construction of DNA molecules by PCR, DNA sequencing, site directed mutagenesis, mammalian cell transfection and establishment of stably expressing cell lines, assay of signal transduction pathways via adenylyl cyclase, phospholipase C, D and A2; isolation of alleles by single stranded conformation polymorphism analysis (SSCP), measurement of intracellular calcium fluxes via fluorescent calcium sensitive dyes, and the generation and assessment of transgenic mice.

Selected Publications

Evellin S, Nolte J, Tysack K, vom Dorp F, Thiel M, Weernink PA, Jakobs KH, Webb EJ, Lomasney JW, Schmidt M. Stimulation of phospholipase C-epsilon by the M3 muscarinic acetylcholine receptor mediated by cyclic AMP and the GTPase Rap2B. J Biol Chem. 277:16805-16813, 2002.

Harrison T, Samuel BU, Akompong T, Hamm H, Mohandas N, Lomasney JW, Haldar K. Erythrocyte G protein-coupled receptor signaling in malarial infection. Science. 301:1734-1736, 2003.

Kobayashi M, Gryczynski Z, Lukomska J, Feng J, Roberts MF, Lakowicz JR, Lomasney JW. Spectroscopic characterization of the EF-hand domain of phospholipase C delta1: Identification of a lipid interacting domain. Arch Biochem Biophys 440:191-203, 2005.

Murphy SC, Hiller NL, Harrison T, Lomasney JW, Mohandas N, Haldar K. Lipid rafts and malaria parasite infection of erythrocytes. Mol Membr Biol. 23:81-8, 2006.

Murthy SN, Chung PH, Lin L, Lomasney JW. Activation of phospholipase Cepsilon by free fatty acids and cross talk with phospholipase D and phospholipase A2. Biochemistry. 45:10987-97, 2006.

Rajangam K, Behanna HA, Hui MJ, Han X, Hulvat JF, Lomasney JW, Stupp SI. Heparin binding nanostructures to promote growth of blood vessels. Nano Lett. 6:2086-90, 2006.


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View more Publications by Jon Lomasney, MD
listed in the National Library of Medicine (PubMed)
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