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#WomenofPenn: Overcoming Setbacks, Challenges of Opening a Lab

Women of Penn October
M. Celeste Simon, PhD, and Sydney M. Shaffer, MD, PhD

Sitting in an office in Penn’s BioMedical Research Building, M. Celeste Simon, PhD, recalls an experience from 27 years ago, when she first walked through the doors of her lab at the University of Chicago.

“It was completely empty. I remember thinking, ‘what do I do first?’” Simon says jokingly.

Over the past three decades, Simon, a world-renowned cellular biologist who joined Penn in 1999, has received numerous awards for her research, which spans cancer cell metabolism, tumor immunology, and the influence of oxygen availability and deprivation on tumor growth. Reflecting on her early career, Simon, a professor of Cell and Developmental Biology and the scientific director of the Abramson Family Cancer Research Institute, notes the excitement and challenges associated with opening a lab.

It’s a feeling that Sydney M. Shaffer, MD, PhD, first experienced in January, when she opened her lab at Penn—right next to Simon’s lab. Shaffer, an assistant professor of Pathology and Laboratory Medicine, focuses on understanding cancer by breaking it down to the level of individuals cells within a tumor. To do this, her lab develops and uses cutting-edge imaging and sequencing technologies to investigate single-cell problems in cancer, such as therapy resistance and invasion.

Simon and Shaffer recently sat down to talk about the challenges of opening a lab, overcoming setbacks, and management strategies.

Q (Shaffer): How did you first get interested in science and cancer biology?

A (Simon): I became fascinated by the prospect of doing research while taking a chemistry course as a junior in high school. For me, the molecular structures and chemical equations provided a real sense of how the world worked. Originally, I planned to major in chemistry in college—but second and third year college-level courses proved daunting. Eventually, I landed on microbiology as a major. During one of my classes, I was captivated by a lecture on tumour virology. I decided to enroll in a graduate program on tumour biology.

Q: If you were able to go back in time to when you first started your lab, what advice would you give to yourself?

A: When I first started my lab at the University of Chicago, I was really fortunate to be embedded in a group of more senior scientists. They really supported me—whether it was reviewing my grants, nominating me for the Howard Hughes Medical Institute (HHMI), and even just making sure I didn’t make a catastrophic decision. They took a proactive role in helping me advance my career and that was extremely helpful.

Still, starting a lab is the biggest challenge I’ve ever faced. I think everyone will tell you the first five years are the most exciting and enjoyable, but also the most challenging. All of the sudden you go from managing your time, to managing five people’s time.

One of the most important pieces of advice I received: stay at the bench. You set the tone of your lab, you set the work ethic. Rather than being in an office, spend most of your time in the lab.

Q: What were some of the challenges you faced? How did you overcome them?

A: We all suffer setbacks. In the moment, they often feel insurmountable. One example I’ll share is from when I was conducting postdoctoral research with Stuart Orkin at Harvard Medical School. I was trying to differentiate embryonic stem cells (ESCs) that were wild type or mutant for a red-cell regulator, with the goal of generating hemoglobinized red blood cells in wild-type cultures and showing that they failed to develop in mutants. It was tedious, and I experienced a lot of failure. At about the two-year mark, when I still had nothing to show, I grew increasingly frustrated and told my husband, Brian, that I was going to quit. I said I might look for work in a bakery, or even become a barmaid. He proposed a vacation to Squam Lake in New Hampshire. When I returned to the lab, I learned that the last-ditch experiment I set up before my vacation had worked. It’s just an example of the importance of perseverance and supportive spouses.

Q: From your publications, it’s clear that you’ve made important contributions across many different areas of cancer biology. When you embarked in these new scientific directions, how did you make that decision? How do you weigh and consider risk?

A: I’ll be honest, more often than not, it was because of fortuitous findings and circumstances. I try to adhere to the idea of being open to opportunities—avoid saying, “oh, well we don’t do that.” The fun of science is exploring new opportunities and discovering unexpected results. I encourage people to be bold enough to jump into new opportunities. Don’t let a feeling of inadequacy prevent you from pursuing a new opportunity.

Going back to my time at Harvard Medical School, I realized I needed to distinguish myself from my mentor. His work focused on red cell development, so I decided to take all the tools we were using and study white cell development. It was a big leap, particularly because I was among the first people using these tools. Shortly after I got to the University of Chicago, I started to receive a number of requests from people who wanted me to help them establish a novel transgenic or gene-targeted mouse strain. The technology was still in its infancy. One day, I went to lunch with a researcher from Northwestern who was talking to me about this new family of what looked like orphan receptors that appeared to be environmental sensors. I was intrigued, and worked with him to knock out a protein called AHR. We then moved onto factors that respond to hypoxia. That’s what ultimately led us into oxygen sensing, and that’s been a unifying theme of my scientific career ever since.

Q: You currently have numerous leadership positions at Penn. How did you learn the skills necessary for these roles?

A: My leadership skills and decision-making have improved with experience. Now, there’s a great opportunity for faculty to participate in leadership training, which I’d strongly recommend.

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