Theodore Friedmann, A.B., M.D.
Shaochun Song, M.D., Ph.D.
The Friedmann laboratory has long been interested in the development of the concepts and techniques of human gene therapy. These interests have taken the form of work in a variety of gene transfer vector systems, most notably the development of the VSV-G pseudotyping methods of retroviruses and more recently the development of self-assembled nanoparticles that enhance gene transfer of naked plasmids or liposomes through the incorporation of envelope protein receptor ligands such as VSV-G or other viral envelope glycoproteins. Previous disease models of interest have included neoplastic, cardiovascular and CNS disorders and now focus on Lesch Nyhan Disease, a neuro-developmental disorder caused by deficiency of the purine biosynthetic enzyme hypoxanthine guanine phosphoribosyltransferase (HPRT) and associated with disordered dopamine neurotransmission in the brain. We are approaching this complex monogenic disease by extensive characterization of the effects of HPRT gene mutations on global gene expression patterns and on the proteome of affected tissues. To understand how the brain development of the dopamine neurotransmitter system goes awry in HPRT deficiency, we are now applying these molecular methods to a study of normal and HPRT-deficient human embryonic stem cells as they differentiate into dopaminergic neurons.
We are also currently carrying out similar extensive studies of the effects of growth factors and anabolic steroids on gene expression and on the proteomes of muscle cells in culture and on mouse muscle and other tissues in vivo. These studies are aimed partly at developing molecular screening methods for gene-based doping in sport.