Ze’ev Ronai, Ph.D., Cancer Center Director at Sanford Burnham Prebys, discusses his vision for the future as well as the many accomplishments of the Center.
As the new Cancer Center director at Sanford Burnham Prebys, can you describe your mission and vision for the Center?
Ronai: It’s clear to me, and to experts who’ve been directly engaged in cancer research over the past couple of decades, that success in solving problems will be driven by collaborative teams. Cancer research has become multidisciplinary and requires expertise in diverse areas. No single lab has all the skill sets that are needed to move discoveries from the lab to the patient.
Our research will be based on clinical problems emerging from patient data that show responsiveness or resistance to therapies, among other factors. We will no longer solely rely on studies of a single molecule or pathway to advance our scientific efforts.
To accomplish these objectives, we are implementing changes to our operations, updating our expectations and improving our technological capabilities. I hope to create the framework for strong research programs that have a direct impact on patients.
Sanford Burnham Prebys is one of 71 NCI-designated Cancer Centers. What makes it unique?
Ronai: Our Cancer Center comprises approximately 30 laboratories. All of them are led by incredibly talented and dedicated researchers who strive to identify new paths to fight cancer. These paths should lead to new targets that can then be coupled with our second-to-none drug discovery center, which enables collaborations that move our basic discoveries to clinical evaluation.
Our uniqueness relies on the exceptional talent of our trainees (graduate students and postdocs) and principal investigators who discover and study innovative pathways that define what makes cancer smarter. They identify how cancer drivers and obstacles for effective therapy can be overcome in a way that has yet to be tried. For example, our partnership with the Prebys (Drug Discovery) Center enables the identification of new drug candidates that can alter subcellular localizations of protein or monitor changes in a protein’s melting temperature in cancer cells, which enables the evaluation of new potential drugs that can rewind the cancer cell to its pre-transformed state.
What is a drug discovery center?
Ronai: The Institute’s Prebys Center for drug discovery and chemical biology is led by a group of industry experts in drug discovery. They are establishing new screening approaches for experimental drugs, improving recently discovered drugs and creating powerful testing platforms that evaluate the most effective means to inhibit disease drivers. When their task is complete, we partner with a pharmaceutical or clinical group for further development and evaluation.
You're not going to find a drug discovery facility like ours anywhere else—this is one thing, among many, that makes us special and unique compared to the other NCI-designated Cancer Centers.
Why is NCI designation important? How successful has Sanford Burnham Prebys been in renewing its designation?
Ronai: NCI’s Cancer Center Support Grant provides the foundation for our Cancer Center operations. The grant has now been renewed eight times, which is no small achievement. These grants are extremely competitive, and thanks to my Cancer Center predecessors, such as Dr. John Reed, who helped revolutionize research in programmed cell death; and Dr. Kristiina Vuori, who launched our drug discovery center, the NCI continues to acknowledge our importance in the constellation of its Cancer Centers program.
Our last renewal focused on embracing more clinical partnerships. It is my mission and vision to enhance these partnerships. To achieve that, most, if not all, members of the Cancer Center will collaborate with a drug discovery lab to help them move a project forward so that it has the propensity to be impactful in the clinic.
Can you provide a few examples of how some of your proposed partnerships will work?
Ronai: Key scientists and researchers from the Prebys Center are joining the Cancer Center. These members bring a fresh and unique perspective to advancing the initial finding from our basic research labs toward drug discovery and marker validation, which will enable new design for monitoring or administering therapy.
Importantly, integrating clinicians from our collaborating oncology groups will provide an important enhancement for disease specific focus groups at our Cancer Center. The integration of clinicians with our Cancer Center faculty and Prebys Center members will not only enable clinical assessment of targets and pathways, evaluation of clinical material (patient samples) but also provide the gateway for new clinical initiatives, the ultimate goal of our research projects. In doing so we will embrace the bench-to-bedside goal to its fullest.
Why is patient data so important to a basic research effort?
Ronai: There has been an evolution of patient data availability, which has more impact than ever before in our research directions and outcomes. This is not single-person data, but rather aggregated data (RNA and DNA) obtained from patient groups—cancer patients who have in common a certain genetic mutation, or patients whose tumors failed therapy as they developed resistance to certain drugs.
Analysis of data is driven by computational power and is, without hesitation, the one field that we biologists and cancer researchers more and more rely on integrate into our research to assure its clinical impact.
As information about patient tumor makeup becomes more available, it allows us to mine it, to understand mechanistically why resistance occurred, or what is common to certain patient populations whose cancers have a high propensity to metastasize. This allows us to directly address unmet clinical needs.
How does the demand for increased computational power impact Sanford Burnham Prebys?
Ronai: The ability to crunch reams of data from one patient to predict the best possible therapy to treat his or her tumor is known as personalized medicine. This information-intensive approach is at the forefront of patient care today and is highly dependent on computational power.
Because we now have the ability to separate tumors into single cells and evaluate the makeup of each cell in a mass, we understand not only the complexity of the tumors, but also how our body—primarily the immune system—is trying to defeat a malignancy. This ability to do cross-comparisons of millions of cells in a tumor has led to new and important research directions.
How will you use bioinformatics to accelerate discovery?
Ronai: Bioinformatics is a competitive field, so it has been a focus of our recruitment efforts to find and hire the best experts. In parallel, I believe that it would be of great benefit if every lab at our Cancer Center has its own bioinformatician. Luckily, the younger generation of trainees are learning these technologies as part of their everyday research. To support these efforts, we will be implementing a bioinformatics training program for our talented young scientists.
In terms of using bioinformatics, there are tremendous repositories of retrospective, or historical, data available through the NCI’s TCGA [The Cancer Genome Atlas] and its National Clinical Trials Network. It is now relatively easy to access this data and download relevant files to quarry them. If we are asking questions at the RNA and DNA level, retrospective datasets such as TCGA are fine. But if we want information at the protein level, we need access to a large collection of human tissue samples, which are more restrictive and often require prospective, or forward-looking, studies.
What are some of the most exciting areas of basic science that are being translated to the clinic?
Ronai: Our Cancer Center researchers have contributed to remarkable developments in therapeutics. Those efforts provided the foundation for a drug that can inhibit triple-negative breast cancers, a very difficult-to-treat form of the disease; we are building the foundation for a clinical trial that is expected to begin with a focus on pancreatic cancer; and we are part of an exciting collaboration with an NCI data science group to assess synthetic lethal algorithms, or pathways that lead to select kill of tumor cells. As mentioned before, facilitating the translation of lab findings through clinical partnerships is a top priority for us.
CRISPR, mRNA vaccines and other advances have revolutionized the field of scientific research. Have there been advances in the Sanford Burnham Prebys labs that have made a special impact?
Ronai: Fundamental research at our Cancer Center led to:
- The understanding of certain aspects of apoptosis, or programmed cell death, which resulted in a number of important discoveries, leading to novel clinical initiatives.
- The discovery of the death-gene Bax and the discovery of the mechanism of the IAP family of proteins, which both underlie novel therapeutic modalities for cancer.
- The discovery of the RGD peptide, which led to the development of drugs for diseases ranging from vascular thrombosis to cancer.
A commitment to Diversity, Equity, and Inclusion is important in cancer research and treatment. How is the Cancer Center integrating the principles of DEI into its programs and research goals?
Ronai: We’re committed to fostering and integrating diversity, equity, and inclusion. Our mission is to promote equal opportunities for all people and to create an environment where everyone can reach their full potential.
We’re working to recognize issues, needs and themes that relate to diversity, and to develop educational resources aimed to increase awareness within the Cancer Center community. We’re seeking to increase the diversity of leadership, faculty and trainees in our research programs by recruiting, retaining and advancing underrepresented populations.
Through high school outreach programs, our Cancer Center also aims to provide cancer research educational opportunities for underrepresented groups in STEM programs.
Any final thoughts?
Ronai: On a personal note, other than being addicted to cancer research, which best defines my last three decades as a scientist, I’m proud to be an example to my peers, whether they are my laboratory teammates or others in my institution.
Mentoring has been an important component in my scientific life, and I take pride in the success of those I’ve assisted earlier in their careers. Scientists I mentored have contributed to the greater community and have become leading researchers, which has been a most heartwarming experience. The cadre of mentees spans all parts of the world, often with examples of very successful leaders/scientists in their own fields.
In my personal life, my wife, Iris, has been at my side for more than 40 years, assuring that our family of three sons—Tomer, Eilon and Yuval—become successful in their own right, while I am trying to advance my own tasks. In my limited free time, I am either flying small planes in the skies of California or nearby states. Perhaps flying high in the sky is prompting the ambition to reach great heights in cancer research.
