Elaine Fuchs was in graduate school when she heard a lecture about growing a never-ending supply of skin cells in the lab. The speaker, Howard Green, didn’t call them epidermal stem cells at that time, rather keratinocytes. Fuchs was immediately hooked. This was what she wanted to research. She went to train in Green’s group at the Massachusetts Institute of Technology, working on what were the first stem cells ever cultured in a lab.
Fuchs has been at the forefront of skin stem cell research ever since. She has innovated new models and approaches to stem cell and disease research, including reversing the process to understand the genetic basis of disease; designing a mouse model of squamous cell carcinoma; and using a virus to add or remove genes from skin stem cells. Now, she and her team are drilling down into the cells that propagate squamous cell carcinoma, a common skin cancer.
Fuchs, who is also an investigator at Howard Hughes Medical Institute, has been recognized at the highest levels for her scientific contributions, including the U.S. National Medal of Science, the L’Oréal-UNESCO for Women in Science Award, and the E.B. Wilson Medal from the American Society for Cell Biology.
In a talk “Stem Cells in Silence, Action and Cancer” on Oct. 1 at the Max Delbrück Center for Molecular Medicine, Fuchs will discuss her ongoing research to understand squamous cell carcinoma stem cells and find new cancer treatment options.
You study cancer stem cells that are responsible for growing tumors. What have you found and what questions are you are currently investigating?
Elaine Fuchs: We have learned those stem cells are under the radar screen of both chemotherapy and immunotherapy. We want to understand the basis for their resistance, because we’ve learned from our studies in mice that cancer relapses from these particular cells. What is it about these cells – where 90% of the cancer is targeted and yet we haven’t ferreted out the nastiest cells – why are these cells able to survive? When the cancer comes back, it usually comes back with a vengeance. We not only want to understand what is protecting the cancer cells, but also if we can ferret out those cells early on in therapy, so the cancer doesn’t come back.
How did you identify the resistant stem cells?
We pulled the tumor apart and we tested different populations of cells until we found a population that, when we introduced even down to a single cell into a mouse, we could develop a squamous cell carcinoma. We then designed attack T cells, called cytotoxic T cells, that would only recognize our particular tumors. We found 90 percent of the tumor disappears very rapidly, but a lingering number of cells remain that just don’t get wiped out. When we examined these resistant cells, we discovered that they are the special tumor-initiating stem cells.
Now you are working out how the cancer stem cells are resisting. What have you found so far?
The tumor cells have an arsenal of various ways of fighting and resisting. The way in which the cells protect themselves from chemotherapy is different from the way they protect themselves from immunotherapy. We have uncovered two of their powerful weapons and we suspect that there are more weapons lurking within those cells.
How could these insights potentially translate to patients?
Our work has led to several potential new ways of treating this particular type of cancer, at least in the mouse and now we want to find out if human cancers behave similarly. If so, there are several cases where it could just be a matter of adjusting the protocol of already approved drugs to ferret out these resistant cells in a patient. If our mouse trials bear that out, then the clinical trials should be relatively straight forward.
You’ve been working in this field for more than 40 years. What do you find most exciting these days?
The field has changed so rapidly. What is exciting to me, as somebody who has been doing research for a long time, is not only watch the accelerated pace of research, but to keep up with it. It’s exhilarating.
You are a strong advocate for junior and women researchers. Why is this important to you?
When I started as an undergraduate, there were three women in my physics class of 200 people. There were very few women, there were fewer role models. When I began as an Assistant Professor at the University of Chicago, there was a famous woman scientist in my division who took the time to write me a handwritten note congratulating me on each small award or fellowship I received. It made a difference that someone with such an honored career was looking out for me. I have retained the importance of that experience throughout my career. As I’ve become more senior, I’ve found it important to support junior faculty of all genders because it makes science better if we are all inclusive and if we try to minimize the amount of dogma that exists within science.
Interview & text: Laura Petersen
MDC Lecture with Elaine Fuchs
Tuesday, October 1, 14:00
Axon 1, MDC.C.
No registration required.