Phenomena or Process: Genome

“I love doing science, and a chance to do some good for the world. Sanford Burnham Prebys is a great place to pursue science.“

Professor at UC San Diego and TSR
Department Head, Molecular Neuroscience, Merck Research Labs

Education

1988-1991: Postdoctoral Fellow, Whitehead Institute/MIT, laboratories of Drs. Rudolf Jaenisch and David Baltimore, Developmental and Molecular Biology
1988: MD, PhD, Stanford University School of Medicine, Neuroscience
1981: B.A., University of Hawaii at Manoa, English and Biology

Honors and Recognition

2016: Alzheimer’s San Diego Courage and Hope Award
2014: Thomson Reuters World’s Most Influential Scientific Minds list of highly cited researchers 
2011: Killam Lecturer, Montreal Neurological Institute 
2010: Journal of Lipid Research Lecturer, Keystone Symposium on Bioactive Lipids: Biochemistry and Diseases, Kyoto, Japan 
2007: Chancellor’s Award for Excellence in Neuroscience, LSU Medical School 
1999-2006: Independent Scientist Award, NIMH 
1994-1999: First Award, NIMH 
1993-1995: Basil O’Connor Scholar (March of Dimes Birth Defects Foundation), UCSD 
1992-1995: Klingenstein Fellow in the Neurosciences, UCSD 
1992-1994: Alfred P. Sloan Research Fellow, UCSD 
1988-1991: Helen Hay Whitney Fellow, Whitehead Institute for Biomedical Research 
1981-1988: Trainee, Medical Scientist Training Program (MSTP), Stanford University School of Medicine 

Related Disease
Alzheimer’s Disease, Hydrocephalus, Multiple Sclerosis

Phenomena or Processes
Aneuploidy, Development and Differentiation, Development of Neuronal Circuits, G-Protein Coupled Receptors, Genome, Lipids, LPA, Mosaicism, S1P, Single Cell

Anatomical Systems and Sites
Brain, Nervous System

Genomic Mosaicism in the Brain
Genomic mosaicism (GM) is a surprising phenomenon whereby cells from the same brain actually have distinct genomes (different DNA sequences). We continue to define forms of GM, involved cell types, and GM’s impact on normal brain function and disease. Diseases of particular interest include Alzheimer’s disease, Down syndrome, Parkinson’s, and other neurodegenerative diseases as well as neuropsychiatric disorders and substance abuse.

Lysophospholipid Receptor Signaling
Lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are small fat molecules that act through G protein-coupled receptors (GPCRs) on the surface of cells. We continue to study fundamental aspects of their signaling properties, and their disease roles in hydrocephalus (water on the brain), neuropsychiatric disorders (schizophrenia, autism), and neurodegenerative disorders (multiple sclerosis, Alzheimer’s disease).

Neuroscience Drug Discovery
From these and other research areas, new therapeutics for diseases of the brain are being pursued, which include identifying new targets, novel biomarkers, and mechanism-of-action studies. This approach successfully aided in the development of the first oral treatment for multiple sclerosis, fingolimod, and related lysophospholipid receptor compounds. Drug discovery efforts include not only small molecules, but also other forms of molecular therapeutics.