Marilyn Farquhar

Affiliation: UCSD SOM

Professor and Chair, Department of Cellular and Molecular Medicine, Professor of Pathology

Biography

Marilyn Gist Farquhar received her A.B. degree in Zoology, and her Ph.D. in Experimental Pathology from the University of California Berkeley. She has previously held positions as Professor of Pathology at the UCSF School of Medicine, Professor of Cell Biology at Rockefeller University, and Sterling Professor of Cell Biology and Pathology at Yale University School of Medicine. Honors include the Wilson Medal of the American Society of Cell Biologists, the Homer Smith Medal of the American Society of Nephrology, the Faculty Research Award of the University of California San Diego, and the A. N. Richards Medal of the International Society of Nephrology for Research in Nephrology. She is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. Currently she is a Professor of Cellular and Molecular Medicine and Pathology, and Chair, Department of Cellular & Molecular Medicine at the UCSD School of Medicine.

Research Summary

The main interests of our lab of cell biology and experimental pathology are focused on 1) the interplay between cell signaling and protein trafficking, and 2) the cellular and molecular mechanisms of renal disease.

Cell Signaling and Protein Trafficking: All cellular processes?normal and pathological?are regulated by extensive signaling networks. We have only recently come to understand that signaling and protein trafficking are irrevocably intertwined. The main theme in our work is that there is considerable spatial regulation of signaling that is mediated by trafficking and targeting events, and trafficking is in turn regulated by signaling molecules. Our overall goal is to understand how cell growth and proliferation are regulated by growth factor and G protein coupled receptor trafficking and signaling. We have discovered a number of new molecules that serve to modulate G protein signaling and to link it to growth factor signaling and trafficking. Our current projects are focused on 1) the regulation of EGF receptor signaling by Galpha S and by RGS-PX1, a GAP for GalphaS and a sorting nexin that regulates endocytosis; 2) the regulation of TrkA, NGF growth factor signaling by GIPC, a scaffold protein that serves to cluster signaling molecules and membrane proteins together; 3) the role of GIPN, an E3 ubiquitin ligase, in down-regulation of G proteins; and 4) the spatial regulation of G protein signaling by targeting of signaling molecules to specific microdomains of the cell membrane and Golgi membranes.

Cellular and Molecular Mechanisms of Renal Disease: The kidney glomerulus serves the vital function of filtering the blood plasma, and the proximal tubule serves to reabsorb and return filtered proteins to the circulation. Renal diseases destroy these functions and lead to death or require drastic treatments such as kidney transplantation or dialysis. A long-standing interest of our laboratory is in understanding the cellular and molecular mechanisms of protein filtration and absorption in health and disease. Here again, our emphasis is on defining the role of signaling and trafficking events in regulation and maintenance of these vital functions. Our current projects in this area are aimed at attempting 1) to define how the membrane protein podocalyxin regulates glomerular epithelial cell (podocyte) architecture in order to understand how mutations or knock-out of podocalyxin leads to kidney disease (nephrotic syndrome); 2) to define the signaling mechanisms by which megalin, the main endocytic receptor in glomerular and proximal tubule epithelia, functions in reabsorption of filtered proteins; and 3) to define the signaling mechanisms by which nephrin, a protein found in the slit diaphragms of the podocytes, regulates the permeability of the slits between the foot processes. We hope that this work will lead to an understanding of how nephrin mutations in humans (Finnish Nephrotic Syndrome) and knock-out mice lead to proteinuria and the nephrotic syndrome.

References

References From PubMed (NCBI)

Training for Careers in Biomedical Research