Introduction

Understanding the brain – how it arises developmentally, how it carries out its myriad complex tasks and how it is affected by diseases represents a major challenge for both basic science and medicine.  Two topic areas with both basic and potentially therapeutic relevance drive our current studies:  the role of lysophospholipid signaling; and the role of genomic alterations within individual neurons, as manifested by aneuploidy. 

Lysophospholipid signaling 

Lysophospholipids are simple phospholipids containing a glycerophosphate or sphingoid backbone and single acyl chain of varied length and saturation.  Two major forms of lysophospholipids are lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P).  It is now clear from the work of our lab and many others that most important actions of lysophospholipids are mediated by cognate G-protein coupled receptors.  The creation of mice null for single and multiple receptors is being used to determine receptor selctivity and physiological function.  Our data has demonstrated roles in nervous sytem development, reproduction, and auditory and vestibular function. Ongoing research is investigating the receptor-mediated signaling mechanisms that mediate the diverse biological functions of LPA and S1P.

Neural Aneuploidy

Are all neurons in the brain genetically identical, as widely assumed or are there differences encoded within individual genomes?  Using a combination of Spectral Karyotyping (SKY), which “paints” chromosomes to allow their unambiguous detection, and fluorescence in situ hybridization (FISH) that utilizes labeled point-probes to identify discrete genetic loci in interphase cells, a substantial degree of genomic variation has been identified in the normal brain. In normal developing brain, chromosome missegregation defects were found, indicating that aneuploidy in neural cells can, at least in part, be accounted for by known mechanisms.  Current work is exploring the functional significance of neural aneuplody during development and in disease processes.

Updated research page, coming soon...
for a general description of our current research, click here.