At Work: Cancer Biologist Johanna Joyce

Johanna Joyce, Cancer Biologist Johanna Joyce, Cancer Biologist -- "My overall goal is to learn how applicable the findings from one tumor environment are to other types of tumors."

Cancer biologist Johanna Joyce investigates how cancer cells interact with their microenvironment and how this affects tumor growth, metastasis and response to therapy. We spoke with Dr. Joyce in 2006, two years after she established her laboratory at the Sloan Kettering Institute.

My entrée into science was not some dramatic eureka moment. For me, the interest had always been there from an early age. While many of my friends struggled with decisions about what to do with their lives, I was lucky to know that I wanted to be a scientist.

When I was a teenager, my family moved from England to Ireland, taking me from cosmopolitan London to the Irish countryside. While this was a huge change for a 14 year old, one very positive outcome was that unlike in the more restrictive English system I had the opportunity to study a far broader range of subjects, including all the sciences. During this time, I was drawn to the field of genetics, finding it fascinating that you could mutate, or “knock out,” genes and produce different observable characteristics in an organism.

Genomic Imprinting & Disease

After completing my bachelor’s degree at Trinity College in Dublin, where I received a good grounding in genetics, I went on to the University of Cambridge. As part of my undergraduate thesis, I had done a literature review on the subject of genomic imprinting. (In genomic imprinting, the expression of certain genes is determined by whether the copy of the gene is inherited from the male or female parent.) I found the subject so fascinating that I knew it would be the focus of my graduate research, and I was fortunate to land at Cambridge, which was a hotspot for studies of genomic imprinting in Europe.

At Cambridge, I had the opportunity to work in the lab of Paul Schofield, an important player in the field of imprinting. In Paul’s lab, we worked on human diseases that resulted from defects in genomic imprinting, such as cancer. My graduate work allowed me to combine my joint interests in cancer genetics and genomic imprinting, both of which, importantly to me, had clinical implications. Moving forward, I wanted to do some real cutting-edge science, and it was this desire that led me to do my postdoctoral fellowship with Douglas Hanahan at the University of California, San Francisco.

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The Importance of the Microenvironment

Doug’s lab was working on mouse models of human cancers, with a focus on angiogenesis — the process by which new blood vessels are formed. At this time, the tumor microenvironment, or the cellular context in which a cancer arises, was being recognized as a key mediator of tumor development. In our work in mouse models of pancreatic islet cell cancer, we showed that a family of enzymes known as cysteine cathepsins, which aid in the breakdown of proteins, plays a critically important role in tumor progression by facilitating angiogenesis and tumor invasion. By inhibiting these enzymes — which we were surprised to discover were predominantly supplied not by the tumor cells but by host innate immune cells — we were able to halt tumor progression.

I wanted to go to an institution that would offer the potential to collaborate with clinical investigators, and as more than an empty promise.
Johanna Joyce Cancer Biologist

Once my postdoc fellowship was completed, I knew that I wanted to go on to an institution that would offer the potential to collaborate with clinical investigators. While many places make this claim, I had the strong sense in interviewing at Sloan Kettering Institute that it was more than just an empty promise, although even I was surprised by the number of collaborative efforts my laboratory would become involved with during our first year alone at Sloan Kettering Institute.

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Cathepsins as a Key Target

When I started my laboratory in the Cancer Biology and Genetics Program in December 2004, my team and I continued my pancreatic islet cell cancer research in collaboration with David Klimstra, Chief of the Surgical Pathology Service at Memorial Sloan Kettering Cancer Center. David supplied an invaluable resource — his collection of approximately 80 pancreatic endocrine tumor tissues (an uncommon type of pancreatic cancer). Studying these human samples, we discovered that the two cathepsins which we had previously identified in mouse models as being responsible for the most extreme reduction in tumor growth when they were mutated were precisely the same two cathepsins that were associated with malignant progression in these human cancers.

Hopefully, this new information can be used to help to refine the design of more precisely targeted therapies in patients with cancer — a goal that we are taking two parallel approaches to achieve. First, we are collaborating with Stanford University’s Matthew Bogyo, who is chemically tweaking the structure of the cathepsin inhibitors in the hope of making them more selective. Second, in collaboration with Hakim Djaballah’s High-Throughput Drug Screening Core Facility at Memorial Sloan Kettering Cancer Center, we are looking for other chemical compounds that may act as successful cathepsin inhibitors. The entire team is working closely with the National Cancer Institute to potentially translate our findings into a Phase I clinical trial.

My overall goal is to learn how applicable the findings from one tumor environment are to other types of tumors. To answer this question, we have recently begun work on prostate cancer with Howard Scher, Chief of the Genitourinary Oncology Service at Memorial Sloan Kettering, and on breast cancer with Memorial Sloan Kettering pathologist William Gerald.

The success of the lab in its first 12 months could not have been achieved without the imagination, hard work, and devotion of my research team. To me, they are true partners. I don’t think there is another institution where I could have attracted such a tremendous group of people; thanks to them we have surpassed my initial first-year hopes and are on track for even greater research successes.

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