ACS and NCI Honor Ruggero for Bold Work in Cancer Research

The NCI Outstanding Investigator Award is another huge honor. You can think of it almost as a lifetime achievement award because, similar to the ACS award, it recognizes past accomplishments and provides long-term support that exceeds the typical grant format. For example, the R35 Award provides seven years of uninterrupted funding. This allows you to commit to projects that are more high-risk and may take a longer time frame to develop. I’m energized by the new possibilities that have opened up in my lab as a result of this new funding.

The overall common thread between the ACS award and the R35 award is my lab’s insight into how protein production goes awry in cancer cells. What our research has shown is that a cancer cell may adapt many more features typical of a virally-infected cell. In particular, when a virus infects a cell, it usurps the protein production machinery, the ribosome, to selectively translate its own viral mRNAs at the expense of other mRNAs in the cell. Thereby, it rewires the cell to become a factory that is geared to selectively producing only viral proteins. Our work suggests that the same remodeling of protein production may be occurring in cancer cells. We, therefore, want to examine how the cancer cell’s translation machinery changes compared to normal cells. With this knowledge at hand, we can better understand how cancer cells selectively churn out proteins that underlie key characteristics unique to cancer cells, such as indefinite growth, metastasis, and resistance to cancer therapies.  

I was raised close to the beach in southern Italy. My earliest passion for biology came from studying sea creatures in the water close to my home. I would dive and collect squid embryos, sea urchins, sea horses, and fish. I was fascinated by the diversity of life and how the body plans of these organisms were established. My parents bought me a simple microscope and I would dissect what I collected after my sea excursions in my room.

I left my hometown to start my undergraduate studies in Rome, largely because I wanted to attend one of the best universities in Italy to carry out biological research. I actually did not start studying cancer at all as I was much more interested in a strange bacterium that grew at extremely high temperatures (90 degrees Celsius) and high pH conditions that would normally burn our skin. I was interested in how this organism survived in such harsh conditions, and I became intrigued by its translation machinery and how this organism could produce proteins that enabled adaptation to these conditions.

Towards the end of my PhD, I became fascinated by the idea that each cell may have evolved to make a more customized translation machinery that could selectively produce proteins that it needed to become a unique cell type. At that time, there were also the first hints that mutations in components of the translation machinery were present in human cancers. I then made a bold move to leave my home country and join the Memorial Sloan Kettering Cancer Center in New York City to pursue this idea. My training in cancer and mouse genetics as a postdoc enabled me to enter a new field, but at the same time my earlier training in biochemistry and basic science equipped me with a unique edge to tackle outstanding questions in the field.

I could have not imagined ending up in a better place than UCSF to conduct my research. The UCSF culture is one of bold risk taking; there is a greater tolerance for pursuing new directions and the idea that nothing is impossible runs pervasively throughout the minds of everyone on campus. Moreover, there is an incredible synergy between basic and clinical research. This perhaps reflects the two halves of my research interests such that I can have great colleagues to discuss basic science with as well as have the opportunity to take our research in very clinical directions. There is a great sense of collegiality and openness, making UCSF a very special place.

I also have been fortunate to have been recruited by Peter Carroll in the urology department, who is an incredible supporter of basic science and our research. He is a visionary to bridge these two worlds, and he has a deep appreciation for how much basic science can contribute to cancer treatments. I could never be where I am right now without his support. Being a part of the urology department has also greatly influenced our research trajectory. For example, we have shifted our efforts to studying fundamental mechanisms of prostate cancer mechanisms. I have been fortunate to have outstanding clinician scientists from the department in the lab that enabled us to translate our basic research findings into the clinic, including establishing new clinical trials for prostate cancer.     

I feel that our greatest contribution to research has been our lab’s vision to study the last step in gene expression and translational control, and its contribution to cancer biology. This has been a much more neglected step in gene regulation that has not been carefully examined in cancer cells. It has been especially challenging to study as it requires the development of new technologies, mouse models, and novel ways of thinking about the problem. When I began this work, I was almost entirely in isolation as this line of research was not broadly being pursued. It has been extremely gratifying seeing this research exponentially grow in recent years and emerge into an entirely new research field, with labs all over the world working on this problem. In the near future, I see it as my mission to help shepherd this field, including members of my own lab who have gone on to establish their own independent laboratories, so that it continues to foster new discoveries essential for understanding cancer development and its treatment. I have been incredibly excited by the overwhelmingly positive response from the NIH and AACR in recognizing the importance of translational control in cancer. For example, I have helped organize several AACR meetings dedicated to this topic as well as fostered new funding initiatives from the NCI.  

My biggest hope is to see some of our research findings translated into the clinic to help cancer patients. Our findings using mouse genetics have provided compelling proof-of-principle of the importance of being able to target key translation factors in cancer cells as a means to thwart the selective production of proteins that drive cancer development. We have made mice whose cells are “untransformable” by some of the most devastating and undruggable oncogenes such as RAS and Myc. These findings suggest that instead of trying to find drugs that work against specific oncogenes, there may be a common downstream “effector” program utilized by many of them to cause cancer. Because this is a very downstream process, then by finding new drugs that target this program, it may be more unlikely that such therapies will acquire resistance in cancer, which is a frequent cause of treatment failure. Inspired by this line of thinking, it has been incredibly gratifying being a co-founder of eFFECTOR Therapeutics, Inc., which is the first biotech company dedicated to the development of clinical compounds that target the translation machinery in cancer. Some of our lead compounds are already in phase I and phase II clinical trials. I’m very excited by the prospect of seeing a positive response in cancer patients undergoing these new treatments.

When I was a child in southern Italy, I not only collected sea creatures to examine them under a microscope, but I also cooked them with my grandmother. She was an amazing cook and spent hours teaching me how to make delicious Italian meals. Therefore, outside of work I still really enjoy cooking and pairing my dishes with great wine. I’m also a bit of a foodie and I love to explore all possible cuisines from all over the world as well as molecular gastronomy. Outside of that, I still love the ocean and the sea. I’m happiest snorkeling or diving. One of the most amazing diving trips I was on was to the blue hole in Belize.

Hard to say, I love science too much! I don’t have an answer yet.