Did you start off as a cancer researcher? If not, what led you to work on cancer-related research topics?
I actually obtained my PhD in cellular neurobiology at Columbia University and did postdoctoral work in glycobiology at Massachusetts Institute of Technology. When I started my own lab, I was analyzing unique carbohydrate modifications and came across an extracellular matrix protein called laminin. From the literature, I learned that laminin is a component of basement membranes, which play a critical role in tumor invasion. At the same time, I become involved with a group of scientists and clinicians who were trying to understand the aggressive behavior of poorly differentiated colon carcinomas. I began to study the role of laminin in this process and to identify laminin receptors, which, at that time, were not known. This circuitous route led me to a career as a cancer biologist, an area in which I had no formal training.
What are the main cancer-related projects you are currently working on?
We are interested in the mechanisms that contribute to the initiation and progression of epithelial-derived tumors (carcinomas), especially those that are aggressive and poorly differentiated. Our research projects emphasize molecular cell biology but derive from the analysis and clinical behavior of carcinomas. We are identifying mechanisms that account for the loss of differentiation and the highly aggressive behavior of these tumors and exploiting the identified mechanisms to improve prognosis and therapy. A major focus of this work is to define the mechanisms that control the genesis and function of cancer stem cells and to understand how these cells contribute to tumor initiation, progression, and recurrence. Within this framework, our main projects include studies in three areas: regulation and function of integrins, vascular endothelial growth factor (VEGF)/neuropilin function and signaling, and ferroptosis resistance.
Regulation and Function of Integrins
We pioneered studies on the a6 integrins (a6b1 and a6b4), which function as receptors for the laminins, a family of extracellular matrix proteins. We want to understand how these integrins contribute to tumor initiation and progression, with an emphasis on cancer stem cells and the role of laminins in the cancer stem cell niche.
VEGF/Neuropilin Function and Signaling
Another major interest of our lab is the ability of VEGF to directly target tumor cells, especially cancer stem cells, and consequently contribute to tumor initiation, progression, and recurrence. This function of VEGF is independent of its role in angiogenesis and mediated primarily by neuropilins, a class of VEGF receptors. We are studying how VEGF/neuropilin signaling affects cancer stem cell function and are targeting neuropilins for therapy.
Ferroptosis Resistance
The survival of carcinoma cells in the tumor microenvironment is a problem of paramount importance in cancer biology and therapy. Aggressive carcinoma cells are dependent on mechanisms that resist ferroptosis, an iron-dependent form of regulated cell death characterized by the accumulation of lipid reactive oxygen species. We are pursuing studies on the cell biological mechanisms that contribute to ferroptosis resistance in carcinomas.
What do you hope to learn from your cancer-related research?
We hope that our work will continue to provide insight into the nature of aggressive carcinomas and reveal new strategies for therapeutic intervention. Our abovementioned work on the therapeutic targeting of neuropilins has shown considerable promise and is the basis of a patent application filed by UMASS.
What do you see as the most promising technology or techniques in cancer research right now?
Cancer research has benefitted enormously from technological advances in molecular and cell biology. In my opinion, it is the combined use of multiple cutting-edge technologies that is having the most impact on cancer research. For example, the ability to analyze gene and protein expression in combination with high-resolution imaging of these molecules provides a molecular and cellular portrait of tumors that can be manipulated using gene-editing techniques.
Where do you see the future of cancer research going?
This is a complex question because many advances will be needed to have a major impact on the morbidity and mortality associated with many cancers. Clearly, immunotherapy is one of the most promising directions as we look to the future. Personally, however, I believe that cancer is fundamentally a disease of cells and cellular interactions. Despite the tremendous amount of knowledge that is being gained from the genetic profiling and analysis of human tumors, the behavior of these tumors and their responses to therapy are determined ultimately at the cellular level in the context of the tumor microenvironment.
How has the cancer field changed or progressed over time?
The most apparent change I have seen is that the study of human tumors has progressed from descriptive to mechanistic analysis. There was a prevailing opinion among basic scientists, 35 years ago, that studying human tumors was not “real science” because it was too descriptive. At the time, seminal discoveries such as the discovery of oncogenes were being made using cultured fibroblasts and cultured cancer cells. This early work laid the foundation for our ability to analyze human tumors at a mechanistic level.
What is the most enjoyable part of your job as a researcher?
The most enjoyable part of my job is the freedom to pursue problems that I find exciting and relevant to our understanding of biology and cancer. I also enjoy mentoring the next generation of cancer researchers — the graduate students and postdoctoral fellows in my lab.
What advice/guidance would you offer to a young student considering a career in cancer research? What are some challenges that young researchers should anticipate?
First and foremost, any student contemplating a career as a cancer researcher should have intellectual curiosity and a passion for science. They should also realize that they are entering a rather competitive field and that a good dose of self-confidence, resilience, and perseverance is needed to succeed.
What is your message to potential donors?
Private donations, either individual or through foundations, have a significant impact on our research programs. At present, federal funding for cancer research is limited and extremely competitive. Very often, private donations help to sustain our research programs and, importantly, provide us with the ability to pursue more novel and risky research that has the potential to have a significant impact on human cancer. My own career, as well as the careers of many of my colleagues, has been helped tremendously by private donations.
About Arthur Mercurio
Arthur Mercurio, PhD, is a professor and Vice Chair of the Department of Molecular, Cell and Cancer Biology at the University of Massachusetts Medical School. Dr. Mercurio obtained a PhD from Columbia University and received postdoctoral training at Massachusetts Institute of Technology.
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