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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/
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Phone: (312) 503-0450
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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.
View more Publications by Jon Lomasney, MD
listed in the National Library of Medicine (PubMed)
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