Jon Lomasney, MD
Associate Professor of Pathology
Associate Professor of Molecular Pharmacology and Biochemistry
Director of Autopsy
303 E. Chicago Avenue
Chicago, IL 60611
Phone: (312) 503-0450
Anatomic Pathology Division
Dartmouth Medical School
Site of Residency
Duke University Medical Center
Site of Fellowship
Duke University Medical Center
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.
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.
Burt RK, Chen YH, Verda L, Lucena C, Navale S, Johnson J, Han X,Lomasney JW, Baker JM, Ngai KL, Kino A, Carr J, Kajstura J, Anversa P. Mitotically inactivated embryonic stem cells can be used as an in vivo feeder layer to nurse damaged myocardium after acute myocardial infarction: a preclinical study.
Circ Res. 2012 Oct 26;111(10):1286-96.
Lomasney JW, Lomasney JW, Cheng HF, Kobayashi M, King K. Structural basis for calcium and phosphatidylserine regulation of phospholipase C d1. Biochemistry. 2012 Mar 20;51(11):2246-57
Sales VL, McCarthy PM, Carr JC, Mehlman DJ, Lomasney JW. Near-complete obstruction of an aortic homograft.
Circulation. 2012 Feb 28;125(8):e392-4.
Ng J, Villuendas R, Cokic I, Schliamser JE, Gordon D, Koduri H, Benefield B, Simon J, Murthy SN, Lomasney JW, Wasserstrom JA, Goldberger JJ, Aistrup GL, Arora R. Autonomic remodeling in the left atrium and pulmonary veins in heart failure: creation of a dynamic substrate for atrial fibrillation.
Circ Arrhythm Electrophysiol. 2011 Jun;4(3):388-96.
Webber MJ, Han X, Murthy SN, Rajangam K, Stupp SI, Lomasney JW. Capturing the stem cell paracrine effect using heparin-presenting nanofibres to treat cardiovascular diseases. J Tissue Eng Regen Med. 2010 Dec;4(8):600-10
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)