For as long as he can remember, Dr. Jeffrey Segall has wanted to know how things work. His fascination with the science behind black holes led him to study biology and physics at Harvard College. He earned his PhD in biophysics from the California Institute of Technology (CalTech), then did a postdoctoral fellowship at the Max Planck Institute of Biochemistry in Germany to understand how cells can detect spatial gradients of molecules.
In 1989, Dr. Segall came to Einstein as an assistant professor in the Department of Anatomy and Structural Biology to join scientists studying signal transduction in various model systems. Over the next 34 years, Dr. Segall's research focused on the mechanisms of tumor cell invasion and metastasis, specifically tumor cell motility and chemotaxis-driven orientation — pivotal aspects in invasion and metastasis in breast cancer, head and neck cancer, and glioblastoma.
Aside from directing his research lab, Dr. Segall has been a dedicated mentor, teacher, and an integral part of the Einstein community, having served many years on the Einstein Senate, including a decade as Speaker. Upon his retirement on July 1 of this year, Dr. Segall transitioned to professor emeritus in the Department of Pathology and stepped down as the Betty and Sheldon Feinberg Senior Faculty Scholar in Cancer Research. In this new career phase - not retiring, but rewiring - he remains accessible, with an office in Block and a keen interest in engaging in collaborative ventures with faculty and students.
Dr. Segall took time last week from his adventures in England with his wife, Theresa Beyer, to reflect on his career at Einstein, including his time in the Senate, share his advice for young scientists, and envision his next chapter. Read the Q&A here.
What sparked your interest/passion for science and cancer-related research?
JS: Kip Thorne's work on black holes (in the 1970s) inspired me to explore the fields of biology and physics. In college, I decided biology was a better fit and went to Howard Berg's lab at Caltech to do a PhD in biophysics of bacterial chemotaxis. That inspired me to understand further how cells can detect spatial gradients of molecules. Therefore, I decided to do a postdoc in Guenther Gerisch's lab at the Max Plank Institute to study Dictyostelium discoideum chemotaxis ("Dicty") since it was a more tractable genetic system at the time.
What led you to Einstein?
JS: Peter Satir (a pioneer in cell and cilia biology) had assembled a department with scientists studying signal transduction in a range of model systems, including John Condeelis, who studied control of actin polymerization in Dictyostelium. At Einstein, John and I started to explore applying what we had learned in Dicty to the chemotactic responses of tumor cells. That collaboration was highly productive, and we continued to focus on studying tumor cell motility and metastasis. I expanded from breast to head and neck cancer, collaborating with Dr. Michael Prystowsky. Ironically, I never thought I would study systems involving animals, but my fascination with tumor biology led to a complete shift in perspective.
Looking back on your career at Einstein, what were the highlights, achievements, breakthroughs, or memorable moments?
JS: Einstein has been an incredibly supportive and exciting place to work. Peter Satir was interested in basic science and supported my side trips into areas such as studying the orientation of yeast mating structures (shmoos). In that case, I applied the techniques used in my bacterial and Dicty studies to yeast mating and directly demonstrated for the first time that yeast were able to orient their mating structures. That inspired several yeast researchers to dissect the mechanisms of how yeast can orient, and the field has developed remarkable insights into the molecular pathways. However, the key achievements were developing the intravital imaging of tumor cells in vivo (in collaboration with John Condeelis) and identifying the paracrine loop mechanism of invasion involving macrophages with many Einstein collaborators. Interestingly, my collaboration with Mike Prystowsky revealed that the paracrine loop may not function in head and neck cancer; mechanisms of invasion can be cancer-specific. Indeed, although I mention John and Mike by name, I have collaborated closely and published with many people at Einstein. The great advantage of being at Einstein was having many collaborators who could stimulate and expand my research.
What are the most significant advancements in your area of research, and what do you see going forward?
JS: In the case of Dictyostelium chemotactic mechanisms, what is remarkable is the dauntingly complex protein network that contributes to chemotactic sensing - perhaps 50 or more proteins regulating more than five separate but inter-regulating pathways. Conversely, in yeast, the focus remains on 10 to 20 proteins. However, in the case of tumor metastasis, like Dicty, many proteins can contribute . On the other hand, the remarkable ‘omics technologies that have developed enable us to accumulate the detailed patient and cell specific information to overcome such challenges. For patients with metastatic cancer, I think we will slowly identify patterns of sensitivity that will be highly patient-specific and continue to improve outcomes.
You served for many years as a leader in the Einstein Senate. How would you characterize the relationship between the Senate and the medical school?
JS: I became a Senator for the Department of Anatomy and Structural Biology in 1994 and then Secretary and Vice Speaker. I was Speaker from 2010 to 2019. Among other things, while I was Speaker, the Senate worked with the administration to develop the tenure policy and supported the transition of Einstein from Yeshiva University to Montefiore. Ideally, we work as partners with the administration. The faculty, students, and postdocs are critical for the success of Einstein. When needed, the Senate can provide a crucial counterweight to the administration, providing an independent voice for the faculty, students, and postdocs to suggest ways to improve Einstein.
What advice do you have for young scientists entering the field today?
JS: It is an exciting time, with remarkable tools and opportunities to expand our understanding of biological systems. Learning new fields and skills will be critical for enabling success. In my case, Peter Satir insisted that the basic scientists should participate in either the anatomy or histology courses. I taught in the histology course (actually ended up directing it for a few years) and the knowledge that I gained about human cell biology was critical for my transition from studying model systems to human cancer. But the competition is fierce, and research is more than a full-time job. And, of course, experiments fail much more often than they succeed. Thus, you need to find a field that grabs you so you can keep going late at night when writing a grant proposal or when a key experiment fails.
Are there any exciting plans for the next chapter?
Right now, I'm following my wife as she plans things she's interested in, such as hiking Hadrian's Wall (a former defensive fortification of the Roman province of Britannia in Northwest England, dating back to AD 122). We passed Milecastle 56 recently. It's a spectacular walk, especially if it's not raining! I am currently the Parliamentarian for the Senate and am interested in putting together the minutes of the Senate since its start in 1969. Following the minutes, one can see how the forces driving biomedical research have changed and how Einstein has evolved in response. I'm also interested in some of the implications of truly accepting natural selection as the driving force for evolution and the consequences for interpreting human behavior.
Posted on: Friday, October 20, 2023