Fuchs accepted a faculty position at the
University of Chicago in 1980 and was the first woman in the biochemistry department. Her first publications there reported the first cloning and sequencing of
keratin cDNAs that characterized the two types of keratins. At the University of Chicago she was mentored and befriended by
Janet Rowley and
Susan Lindquist; they eventually all joined the reorganized Department of Molecular Genetics and Cell Biology, in which Fuchs was ultimately appointed the Amgen Professor of Molecular Genetics and Cell Biology. In 2002, Fuchs accepted a position at
Rockefeller University, where she is currently the Rebecca C. Lancefield Professor of Mammalian Cell Biology and Development and an investigator at the
Howard Hughes Medical Institute. Fuchs is known for her study of skin, identifying the molecular mechanisms underlying skin disease, developing the field of skin stem cells, and pioneering reverse genetics. Her research group uses
laboratory mice and mammalian epithelial stem cell culture as
model systems. Recently, she has been devoting her research to studies on the role stem cells play in the regeneration of tissue, as well as the competing demands of proliferation and differentiation in maintaining enough stem cells. Fuchs currently sits on the board of the
Damon Runyon Cancer Research Foundation. She was elected president of the
American Society for Cell Biology in 2001. In 2009 Fuchs was awarded the United States’ highest honor for scientific contributions, the
National Medal of Science, by President
Barack Obama. In 2015 she was awarded the American Society for Cell Biology's highest scientific honor, the
E.B Wilson Medal. In 2020 she received the
Canada Gairdner International Award.
Reverse genetics Fuchs developed the
reverse genetics approach when she began as an assistant professor at the University of Chicago. Reverse genetics seeks to understand the genetic basis of a disease by examining how specific genetic modifications (such as the use of
transgenes) affect phenotype, as opposed to
forward genetics, which searches for genetic explanations to a specific phenotype. Fuchs first applied the technique by engineering a gene that affected keratin function and disrupted the framework of cells. Inserting this mutant keratin into transgenic mice caused heavy epidermal blistering; analysis showed this blistering to be nearly identical to the dermatological disorder
epidermolysis bullosa simplex. Subsequent collaboration with dermatologists to obtain skin samples from patients with the dermatological disorder revealed that a similar mutation in keratin genes indeed underlies the condition.
Stem cells in squamous cell carcinomas Fuchs and her team have conducted research on how cancerous stem cells called
squamous cell carcinomas (SCCs), some of the most common and dangerous cancers worldwide, interact with their microenvironments. By examining skin cancer in mice, she concluded that the speed at which stem cells will divide and how they divide is dependent on their niche. She examined the inhibitory signaling molecule
TGF-β, which is found near the blood vessels of a tumor. Although the effects of TGF-β and how it restrains normal skin cell growth had been studied by researchers before Fuchs, she specifically looked at the intermediate steps of tumor progression by creating a TGF-β reporter system. She accomplished this by developing tumor cells that expressed a gene commonly found in skin cancer cells, HRasD12V. Her research demonstrated that cancerous stem cells lacking the TGF-β signal proliferate more quickly but are sensitive to
antiproliferative drugs. In contrast, cancerous stem cells that received the TGF-β signal proliferated at a slower rate than those lacking the TGF-β signal but were resistant to antiproliferative drugs. Fuchs determined that both the factors internal to the cell and the cell's external surrounding environment have an effect on the stem cells’ niche in both their ability to divide and how they divide. == Personal life ==