Our research interests lie in the broad area of understanding the biochemical basis of the signal transduction pathways that regulate cell growth. This work is aimed primarily at the analysis of the function of the intracellular protooncogene products, and extends into studies of the common signals that may regulate certain types of cancer cell growth, differentiation and hypertrophy. Over the past 20 years we have contributed to the understanding of the molecular and cellular regulatory processes relating to the cytoskeleton and myogenesis, growth regulation by the Ras oncogene protein and other G-protein elements, protein kinase activities in living cells, and cell cycle regulation at the G1/S boundary.

Our work is currently focused on two areas of research: control of growth and differentiation of the human tumor, rhabdomyosarcoma (RMS), and regulation of cell growth in the pre-cancerous lesion of the human eye, called pterygium. Through the combination of molecular studies in cell culture models and ectopic gene expression, we are making inroads into the understanding of the molecular basis of these diseases. In rhabdomyosarcoma cells, many show normal expression of myogenic factors such as Myo D. In spite of this, the cells fail to growth arrest and differentiate when exposed to signals which should stimulate these events. By exploring the molecular and cellular responses (or lack thereof) of RMS cells to these cues, we hope to determine the molecular basis of this failure. For pterygium, we have established cell culture models and have begun to identify the expression patterns of important growth regulatory genes in both the normal precursor cells and the diseased pterygial cells. By these determinations and by alteration of the expression of these genes, we hope to establish the molecular basis of the abnormal growth of these cells as well.

Over the past several years, we have developed new approaches to examine the function of intracellular proteins. The main tactic has been to use somatic cell microinjection facilitated by glass capillaries. This work has allowed for the facile introduction of purified proteins, genes or inhibitory antibodies into living cultured cells, and has aided in the discovery of biological activities of several key intracellular signal transduction proteins. We believe that this type of functional analysis of the signal pathways that regulate certain differentiated functions will prove to be critical in the understanding of these biological functions.

Dr. Feramisco received his B.A. in Chemistry, his B.S. in Biochemistry, and his Ph.D. in Biochemistry from the University of California Davis. Academic History: Postdoctoral Fellow, and Senior Staff Scientist at Cold Spring Harbor Laboratory; Associate Director for Basic Research at the University of California San Diego Cancer Center; currently a Professor of Medicine and Pharmacology, and an Affiliate Member of Cellular & Molecular Medicine at the University of California San Diego.