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A Conversation with Elaine Fuchs CONVERSATIONS WITH GIANTS IN MEDICINE A conversation with Elaine Fuchs The cell biologist Elaine Fuchs of the have gotten there had I chose that path. Rockefeller University is best known for My default pathway was graduate school, revolutionizing the molecular and genet- and this seemed like the best option. ic study of skin. Her research has shed JCI: How did you choose Princeton light on dermatologic disorders and all and biochemistry for your PhD? aspects of skin growth and regeneration. Fuchs: Fortunate naiveté. I hadn’t really Her more recent work in stem cell biol- carefully planned out what I wanted to do; I ogy has revealed broad paradigms that was so convinced that I wasn’t going to be regulate tissue regenerative stem cells going to graduate school. I did well at the across the body, and the mechanisms she University of Illinois, but had I known just has described have major ramifications how exceptional the scientists were who in cancer and regenerative medicine. were just starting at the time at Princeton Watch the full interview with Fuchs (Fig- and moving up through the ranks, I proba- ure 1) on the JCI website: https://www.jci. bly would have been too intimidated. org/videos/cgms. I needed to work with someone who JCI: Where did you grow up? Figure 1. Elaine Fuchs. could teach me how to do well-controlled Fuchs: I grew up in a small town just experiments and to think like a biologist. outside of Chicago, surrounded by fields My PhD thesis in Charles Gilvarg’s lab was of corn and trees. I grew up with a father Fuchs: Back when I was a high school on bacterial sporulation. I looked at how who was a geochemist, working on extra- student, I went to my dad and asked if I bacterial spores transitioned to a vegetative terrestrial minerals. He looked at the lunar could apply to different universities. He state, and how they broke down their cell samples, there was nothing there that asked me to come up with a several-thou- wall and had to rebuild one that was com- wasn’t found on Earth, whereas meteor- sand-dollar-a-year reason as to why I want- patible with cell division. It was looking at ites coming from billions of miles away ed to go anywhere besides the University how cells transition from a quiescent state to hit the earth were gold mines for a geo- of Illinois where I would get a scholarship, to an actively proliferating state. That’s a chemist of his expertise. or the University of Chicago where as his thread that goes through my whole career. JCI: Did he impact your trajectory? daughter, I had a tuition break, because he JCI: You transitioned to Howard Fuchs: To some extent, yes. Not had been a student there. Since everyone Green’s lab at MIT and mammalian epi- through his geochemistry or his electron in my family (except my mother) had gone thelial biology. diffraction patterns, but through his abil- to the University of Chicago, I rebelled and Fuchs: I heard a lecture by him when ity to recognize rocks that would contain went to the University of Illinois. I was at Princeton, wherein he described fossils. When I was young, he took my Ironically, I never took biology the putting into culture a piece of human skin, sister and me to the quarries around the whole time I was at university. I got hooked resulting in cells that he could passage end- Chicago suburbs to collect rocks. He’d on physics and physical chemistry, and I lessly without their losing their ability to put a few rocks in our bags that he knew loved it. During this time, I was also active differentiate and make skin. To me that was would contain fossils, unbeknownst to us. in Vietnam War protests. phenomenal. He didn’t call them stem cells He would then crack open our rocks to let JCI: You applied to the Peace Corps … at the time, but these were the very first us see the fossils. Regarding careers, my but ended up in graduate school. stem cells ever cultured. father thought I would be a good secretary Fuchs: I was intrigued by Chile because JCI: Did you think you were going to or elementary school teacher. On the other Salvador Allende was in reign. Chile had a stay on the academic professorial path? hand, my father’s sister was not admitted Marxist government, and yet they also had Fuchs: I did not think I had the ability. into medical school and became a tech- a 200-year history of democracy. I started As I was developing as a postdoc at MIT, nician at Argonne National Laboratories. to read about Allende and Chile and I started to get the sense that I really did She was an early pioneer in the feminist thought I would really like to go to there. like biology. At that point, I can remember movement, and she had a huge impact on I put all the measures in place and then thinking, “Well, if one day I have a little lab- my confidence as a woman. got my Peace Corps notice: Uganda. Idi oratory in some small college, maybe with JCI: How did you decide to major in Amin was the President and was a tyrant. a student or two, that might be something physical chemistry at the University of He jailed and then kicked out all the Peace that would be really satisfying.” Illinois? Corp workers six months after I would JCI: And yet you ended up at the Univer- sity of Chicago for your first faculty position. Fuchs: It’s ironic, given that I said I Copyright: © 2019, American Society for Clinical Investigation. chose definitively not to go there as an Reference information: J Clin Invest. 2019;129(11):4551–4552. https://doi.org/10.1172/JCI133402. undergraduate. My graduate advisor, who jci.org Volume 129 Number 11 November 2019 4551 CONVERSATIONS WITH GIANTS IN MEDICINE The Journal of Clinical Investigation interestingly enough thought women didn’t mutation that causes the disease—once Mina Bissell stood up and told the audi- belong in science, suggested that I apply. He found, it was often unclear how the protein ence, “Look, I don’t know if she’s right, had gotten an invitation to submit a nom- contributed to the disease. Instead, I wanted but science will figure it out. I thought her ination, and I don’t think he really thought to start with my protein. What was it doing talk was interesting.” John Stanley (then I would get the job. I was one year into my in cells? To me that was the fun part. Chairman of Dermatology at UPenn) then postdoc, so I really was not looking for a job. Soon, we had put our mutant pro- stood up and said, “Actually I would make I treated it as a free trip home to visit fami- teins in our stem cells in a dish, but we the same diagnosis that Elaine did.” That ly. Still, I prepared, taking it as my trial run couldn’t link this to a human disease. To was a turning point in my career, because for whenever I was going to properly apply. do so, we thought we might be able to put it made me recognize the importance of I can only look back and wonder why they our mutant genes into the skin of mice to facing not-so-friendly fire on the podium ever gave me the job, but I think they were help guide us to the human etiology. It was and speaking up to justify your science and impressed when they asked me where else clear that transgenic and knockout mice conclusions. In so doing, others will likely I was applying, and I said, “Nowhere,” and I were coming on the scene for biological follow, and in this case, they were import- think they took that as a sign of confidence. research. We weighed them both and the ant people in the field. I think it makes a JCI: How did you decide the topic for mutations that we were working on act- difference to the whole community. your lab’s path? ed in a dominant negative way and so we JCI: What does the next 5–10 years Fuchs: That was clear from the get-go thought transgenic mice would be best. No hold for your lab? from the path of my postdoctoral studies. one at the University of Chicago was using Fuchs: We’re really excited about I had tried two different projects that How- these approaches, but I phoned the only the medical implications of our work. ard Green had wanted me to do. One was person in the Chicago area with the exper- We know where tumor-initiating cells of to find additional growth factors; we had tise, and she kindly allowed us to buy and cancers reside, how they resist chemo- known that EGF was important in propagat- set up a microscope in her lab and allow my therapy, and how they resist immuno- ing the cells in culture. Howard very wisely student to learn the technology. Once we therapy. That has told us that if we dig thought there might be additional growth had things up and running, we moved back deeper and understand more about these factors that could stimulate these cells, and to my lab and set up the technology at the cells and how they resist various differ- there were two places to find them.
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