Marilyn Farquhar
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Marilyn Gist Farquhar (July 11, 1928 – November 23, 2019) was a pathologist and cellular biologist, Professor of Cellular and Molecular Medicine and Pathology, as well as the chair of the Department of Cellular and Molecular Medicine at the
University of California, San Diego School of Medicine The University of California San Diego School of Medicine is the graduate medical school of the University of California, San Diego. It was the third medical school in the University of California system, after those established at UCSF and UCLA ...
, who previously worked at
Yale University Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wo ...
from 1973 to 1990. She has won the E. B. Wilson Medal and the
FASEB Excellence in Science Award The Excellence in Science Award was established by the Federation of American Societies for Experimental Biology (FASEB) in 1989 to recognize outstanding achievement by women in biological science. All women who are members of one or more of the so ...
. She was married to Nobel Laureate George Emil Palade from 1970 to his death in 2008. Her research focuses on control of intracellular membrane traffic and the molecular pathogenesis of auto immune kidney diseases. She has yielded a number of discoveries in basic biomedical research including: mechanisms of kidney disease, organization of functions that attach cells to one another, and mechanisms of secretions.


Early life

Marilyn Gist Farquhar was born on 11 July 1928 and was raised in the Central Valley farming community of
Tulare, California Tulare ( ) is a city in Tulare County, California. The population was 68,875 at the 2020 census. It is located in the heart of the San Joaquin Valley, eight miles south of Visalia and sixty miles north of Bakersfield. The city is named for th ...
.Oakes, Elizabeth. ''Encyclopedia of World Scientists.'' Facts on File, 2007, p.224 Her father was from a pioneer family and worked as an insurance agent and farmer, who spent his free time writing novels. Her mother was also from a pioneer family and had begun college, but had to return home before completing her degree.Sedwick, Caitlin
“Marilyn Farquhar: From the beginning”
“The Rockefeller University Press”, 25 Nov. 2013
Farquhar attributes her desire to pursue a career in medicine and biology to her mother's friend, Frances Zumwalt, who was a pediatrician.


Education and career

Farquhar received her undergraduate degree in
zoology Zoology ()The pronunciation of zoology as is usually regarded as nonstandard, though it is not uncommon. is the branch of biology that studies the Animal, animal kingdom, including the anatomy, structure, embryology, evolution, Biological clas ...
and
experimental pathology Experimental pathology, also known as investigative pathology, is the scientific study of disease processes through the microscopic or molecular examination of organs, tissues, cells, or body fluids from diseased organisms. It is closely related ...
from the
University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
. After graduation, Farquhar was admitted to the medical school at the
University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public land-grant research university in Berkeley, California. Established in 1868 as the University of California, it is the state's first land-grant u ...
.“Marilyn Gist Farquhar”
, “The American Society for Cell Biology”, 1995
In 1951, Farquhar married another medical student, with whom she had two sons. However, after two years of medical school, Farquhar shifted to a Ph.D. program where she completed her degree in
experimental pathology Experimental pathology, also known as investigative pathology, is the scientific study of disease processes through the microscopic or molecular examination of organs, tissues, cells, or body fluids from diseased organisms. It is closely related ...
in 1955.Wayne, Tiffany. ''American Women of Science Since 1990.'' Greenwood Publishing Group, 2011, p. 384-386 During her time as a graduate student, she worked in the laboratory as a junior research pathologist and then an assistant research pathologist, after completing her Ph.D., under a pathology professor who was interested in glomerular disease. Farquhar later collaborated with the
University of Minnesota The University of Minnesota, formally the University of Minnesota, Twin Cities, (UMN Twin Cities, the U of M, or Minnesota) is a public university, public Land-grant university, land-grant research university in the Minneapolis–Saint Paul, Tw ...
as a research to study renal biopsies, where they were the first to see glomerular pathology at the
electron microscope An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
level. In 1958, she left the
University of California, San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It cond ...
to do post-doctoral work as a research associate in
cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
at
Rockefeller University The Rockefeller University is a private biomedical research and graduate-only university in New York City, New York. It focuses primarily on the biological and medical sciences and provides doctoral and postdoctoral education. It is classif ...
under George Palade. At the time, many pioneers in cell biology had worked or were currently working in this lab, where there were new discoveries almost every day due to the recent innovation of the
electron microscope An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
. George Palade was working on the kidney glomerulus at the time and provided Farquhar with formal training in the field of cell biology. Together Farquhar and Palade named
tight junctions Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...
and
adherens junctions Adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions, cell–matrix junctions in epithelial and endothelial tissues, usually more basal than tight junctions. ...
. Since then, Farquhar has continued to study junctions in the podocytes. After leaving Rockefeller in 1962, she established her own laboratory at the
University of California, San Francisco The University of California, San Francisco (UCSF) is a public land-grant research university in San Francisco, California. It is part of the University of California system and is dedicated entirely to health science and life science. It cond ...
where she became a Professor of Pathology. Her lab focused on using tracers and
cytochemistry Cytochemistry is the branch of cell biology dealing with the detection of cell constituents by means of biochemical analysis and visualization techniques. This is the study of the localization of cellular components through the use of staining me ...
to investigate the secretory process in pituitary cells and
leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
. This work yielded the first description of crinophagy, the process by which secretory granules are taken up and disposed of in multivesicular bodies and
lysosomes A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prote ...
. In 1970, she divorced her first husband and married George Palade when she decided to take a sabbatical back at Rockefeller University. At the time, she was the only woman professor when she was then appointed Professor of Cell Biology. In 1973, Farquhar returned to the University of California at San Francisco, where she remained as a professor of
cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...
and
pathology Pathology is the study of the causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in ...
for the next 15 years. In 1987, she jointed Palade at
Yale Yale University is a private research university in New Haven, Connecticut. Established in 1701 as the Collegiate School, it is the third-oldest institution of higher education in the United States and among the most prestigious in the wor ...
where she became Sterling Professor of Cell Biology and Pathology. Here she built a new Department of Cell Biology in the medical school with George Palade and James D. Jamieson. While at Yale, Farquhar's research focused on secretory granule membranes that merge with cell membranes during exocytosis. She also identified several glomerular components that play a role in glomerular functions. In 1990, Farquhar and Palade returned home to California to help build and strengthen cell and molecular biology at the
University of California, San Diego School of Medicine The University of California San Diego School of Medicine is the graduate medical school of the University of California, San Diego. It was the third medical school in the University of California system, after those established at UCSF and UCLA ...
. Farquhar was a Professor of Cellular and Molecular Medicine and Pathology, as well as the chair of the Department of Cellular and Molecular Medicine at the
University of California, San Diego School of Medicine The University of California San Diego School of Medicine is the graduate medical school of the University of California, San Diego. It was the third medical school in the University of California system, after those established at UCSF and UCLA ...
. Her focus was on a molecule called GIV that regulates cell migration in response to
growth factors A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
and determines the fate of growth factor receptors. Throughout Farquhar's lifetime, she has witnessed and helped guide the evolution of the field of cellular biology.


Research

Throughout Farquhar's career, her lab maintained two research interests – control of intracellular membrane traffic and the molecular
pathogenesis Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...
of
autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
kidney diseases. However, Farquhar's research spans numerous areas including
electron microscopy An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
, cell secretion, intracellular membrane traffic, and glomerular permeability and pathology. Farquhar's research yielded a number of discoveries in basic biomedical research, including mechanisms of
kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
, organization of functions that attach cells to one another, and the mechanisms of secretions. The Farquhar Lab was in the Department of Cellular and Molecular Medicine at the
University of California, San Diego The University of California, San Diego (UC San Diego or colloquially, UCSD) is a public university, public Land-grant university, land-grant research university in San Diego, California. Established in 1960 near the pre-existing Scripps Insti ...
, and studied signaling networks that regulate
secretion 440px Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical ...
,
endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
,
autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
,
cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...
and
cancer metastasis Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
. Within these signaling networks, the research focus is on the interplay between G protein and
growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for regu ...
signaling.Farquhar, Marilyn
“Research”
Recently Farquhar discovered molecules involved in novel G-protein mediated signaling pathways. These new proteins modulate G protein signaling and link G-protein signaling to growth factor receptor trafficking.Farquhar, Marilyn

UC San Diego School of Medicine.
The long-term goal is to advance understanding of the role of
G proteins G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their ac ...
in regulating cell processes in health and disease. The other area of interest is focused on the podocyte, or glomerular epithelial cell. The current research is focused on three projects. The first is defining trafficking and signaling mechanisms of
megalin Low density lipoprotein receptor-related protein 2 also known as LRP-2 or megalin is a protein which in humans is encoded by the ''LRP2'' gene. Function LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman neph ...
. The second project is to define the role of
podocalyxin Podocalyxin, a sialoglycoprotein, is thought to be the major constituent of the glycocalyx of podocytes in the glomerulus (Bowman's capsule) in the kidneys. It is a member of the CD34 family of transmembrane sialomucins. It coats the secondary foo ...
in the regulation of podocyte architecture in normal and animals with
kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
(nephrotic syndrome). The last project is examining the interactions and pathology of
nephrin Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is ...
, a protein found in podocytes. The long-term goal for these three projects is to define the molecular mechanisms of glomerular filtration and protein absorption under normal and pathogenic conditions. Her research was funded by grants from the
National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
, the Susan Komen Foundation for Breast Cancer Research, and the National Institute of Diabetes, Digestive and Kidney Diseases.


Awards

* 1981 - President of
American Society of Cell Biology The American Society for Cell Biology (ASCB) is a professional society that was founded in 1960.E.B. Wilson Medal The E.B. Wilson Medal is the American Society for Cell Biology's highest honor for science and is presented at the Annual Meeting of the Society for significant and far-reaching contributions to cell biology over the course of a career. It is name ...
of the American Society of Cell Biology * 1988 - Homer Smith Medal of the American Society of Nephrology * 1987 - Distinguished Scientist Medal of the Electron Microscopy Society of America * 1988 -
National Institutes of Health Merit Award The NIH MERIT award (Method To Extend Research in Time) Award (R37) was created by the National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary age ...
* 1991 - Elected to the
American Academy of Arts and Sciences The American Academy of Arts and Sciences (abbreviation: AAA&S) is one of the oldest learned societies in the United States. It was founded in 1780 during the American Revolution by John Adams, John Hancock, James Bowdoin, Andrew Oliver, and ...
* 1997 - Chancellor's award for Excellence in Research at UCSD * 1999 - Gomori Award from The Histochemical Society * 2001 - Rous-Whipple Award of the American Society for Investigative Pathology * 2006 - Federation of American Societies of Experimental Biology Award for Excellence in Science * 2017 - Revelle Medal


Selected publications

# Farquhar, M.G. 2012. A Man for All Seasons: Reflections on the Life and Legacy of George Palade. Annu Rev Cell Dev Biol. Volume 28. In Press. # Ghosh, P, Garcia-Marcos, M., and M.G. Farquhar. 2011. GIV/Girdin is a rheostat that fine-tunes growth factor signals during tumor progression. Cell Adhes. Migr. 5(3):237-48. # García-Marcos, M., Ghosh, P., and M.G. Farquhar. 2009. GIV is a non-receptor GEF factor for Galphai with a unique motif that regulates Akt signaling. PNAS. 106(9):3178-83. # Head BP, Patel HH, Roth DM, Murray F, Swaney JS, Niesman IR, Farquhar MG, Insel PA. Microtubules and actin microfilaments regulate lipid raft/caveolae localization of adenylyl cyclase signaling components. J Biol Chem. 2006 Jul 3; # Farquhar, M. G. 2006. The glomerular basement membrane: not gone, just forgotten. J. Clin. Invest. 116:2090-2093. # Zhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H. 2005. Nicastrin is critical for stability and trafficking but not association of other presenilin/g-secretase components. J. Biol. Chem. 280:17020-17026. # Lehtonen, S., Ryan, J. J, Kudlicka, K., Iino, N., Zhou, H., and M. G. Farquhar. 2005. Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex. Proc. Natl. Acad. Sci. 102:9814-19. # Head, B. P., Patel, H. H., Roth, D. M., Niesman, I. R., Farquhar, M. G. and P. A. Insel. 2005. G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. J. Biol. Chem. 280: 31036-44. # Rader, K., Boyer, A. D., Farquhar, M. G., and K. C. Arden. 2000. Assignment of ankyrin repeat, family A (RFXANK-like) 2 (ANKRA2) to human chromosome 5q12-q13 by radiation hybrid mapping and somatic cell hybrid PCR. Cytogenet. Cell Genet. 89:164-165. # Zheng, B., Chen, D. and M.G. Farquhar. 2000. MIR16, a putative membrane glycerophosphodiester phosphodiesterase, interacts with RGS16. Proc. Natl. Acad. Sci. 97:3999-4004. # Farquhar, M.G. 1996. Molecular analysis of the pathologic autoimmune antigens of Heymann nephritis. Am. J. Path. 148:1331-1337. # Kerjaschki, D., R. Ullrich, M. Exner, R.A. Orlando and M.G. Farquhar 1996. Induction of passive Heymann nephritis with antibodies specific for synthetic peptides. J. Exp. Med. 183:2007-2016. # Jin, M.J., Saucan, L., Farquhar, M.G., and Palade, G.E. 1996. Rab1a and multiple other rab proteins are associated with the transcytotic pathway in rat liver. J. Biol. Chem. 271:30105-30113.


References


Further reading

*


External links


Bio at Farquhar labDorothy Ford Bainton, Pradipta Ghosh, and Samuel C. Silverstein, "Marilyn Gist Farquhar", Biographical Memoirs of the National Academy of Sciences (2021)
{{DEFAULTSORT:Farquhar, M 1928 births 2019 deaths American women biologists American pathologists University of California, Berkeley alumni University of California, San Diego faculty 21st-century American biologists Yale Sterling Professors Cell biologists American women academics 21st-century American women