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David Tuveson, Director of the Cancer Center at Cold Spring Harbor Laboratory, is a clinician-scientist with a longstanding interest in understanding and treating pancreatic cancer. Since developing the first mouse model of pancreatic cancer in 2002, the Tuveson lab has made a series of discoveries that shed light on the molecular drivers of this disease and provide promising therapeutic avenues for a malignancy that is notoriously challenging to treat. In collaboration with Hans Clevers, David developed the first pancreatic cancer organoids, which revolutionized the field by providing a powerful model system for basic discoveries and advancement of personalized medicine. Here, David talks to Ross Cagan about his path from chemistry student to world-renowned oncologist, highlighting how his colleagues, mentors and patient interactions shaped his research interests and unique approach to scientific discovery. As well as discussing the story behind some of his breakthroughs, he provides tips on running a lab and succeeding in or outside academia., Summary: David Tuveson describes some of the key moments and breakthroughs in his remarkable career, and the path that he's followed in his quest for a cure for pancreatic cancer.

Louis Kunkel has devoted his career to understanding the causes, mechanisms and treatment of muscular dystrophies. Dr Kunkel is the past Director of the Genomics Program at Boston Children's Hospital and Professor of Genetics and Pediatrics at Harvard Medical School. In this interview, he talks about his discovery of dystrophin, including patients in preclinical research, and bearded irises.

Huda Zoghbi's achievements in the field of neurology are internationally acclaimed. She is best known for elucidating the genetic basis of two complex neurological disorders, spinocerebellar ataxia type 1 and Rett syndrome, and has been honored with many prizes, including The Shaw Prize in Life Science and Medicine in 2016 and the 2017 Breakthrough Prize for Life Sciences. A diligent and creative research scientist at the bench, a respected lab mentor and founding Director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, her inspiration has always been the burning need to help patients faced with devastating neurological problems. Her pursuit of the mechanisms mediating spinocerebellar ataxia and Rett syndrome has been dogged, requiring 30 years of focused effort. As highlighted in this interview, her work is now paying dividends by starting to reveal potential therapeutic targets for these intractable and complex disorders., Summary: Huda Zoghbi discusses her remarkable journey from the clinic to the bench, highlighting the experiences and collaborations that inspired her interest in neurological diseases such as spinocerebellar ataxia type 1 (SCA1) and Rett syndrome.

Tatsushi Igaki is currently based at the Kyoto University Graduate School of Biostudies, where he leads a research group dedicated to using Drosophila genetics to build a picture of the cell-cell communications underlying the establishment and maintenance of multicellular systems. His work has provided insight into the molecular bases of cell competition in the context of development and tumorigenesis, including the landmark discovery that oncogenic cells communicate with normal cells in the tumor microenvironment to induce tumor progression in a non-autonomous fashion. In this interview, he describes his career path, highlighting the shift in his research focus from the basic principles of apoptosis to clonal evolution in cancer, and also explains why Drosophila provides a powerful model system for studying cancer biology., Summary: We spoke to Tatsushi Igaki about his research using Drosophila models to uncover the principles of cell-cell communication in development and cancer. He describes his passion for research and the key events that shaped his career.

Scott W. Lowe is currently principal investigator at the Memorial Sloan-Kettering Cancer Center. After beginning his studies in chemical engineering, he decided to take another path and became fascinated by biochemistry, genetics and molecular biology, which ultimately led to an interest in human disease, particularly cancer. During his PhD at the Massachusetts Institute of Technology (MIT), Scott had the opportunity to benefit from the exceptional mentorship of Earl Ruley, David Housman and Tyler Jacks, and contributed to elucidating how the p53 (TP53) tumor suppressor gene limits oncogenic transformation and modulates the cytotoxic response to conventional chemotherapy. This important work earned him a fellowship from the Cold Spring Harbor Laboratory, which helped to launch his independent career. Scott is now a leading scientist in the cancer field and his work has helped to shed light on mechanisms of cell apoptosis and senescence to better understand and treat cancer. In this interview, he talks about this incredible scientific journey.

Owen Sansom, Deputy Director of the Cancer Research UK Beatson Institute, began his research career investigating the molecular mechanisms of apoptosis. Over the course of his work he has moved progressively into a more translational arena, and the current focus of his lab is to understand the signalling pathways underlying colorectal and pancreatic cancers. The Sansom lab uses mouse models to pinpoint how mutations that commonly occur in these frequently deadly cancers co-operate to promote tumorigenesis in vivo. This work has provided many important insights into the molecular changes associated with intestinal and pancreatic neoplasia and has revealed new targets for drug development. Here, Owen tells the stories behind some of his most exciting breakthroughs, describes the experiences and mentors that shaped his research interests and style of running a lab, and discusses the challenges of recapitulating the complexity of cancer as well as translating preclinical evidence to patient therapies.

Lewis C. Cantley, Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, is a world leader in cancer and metabolic disease research. His seminal discoveries have shed light on the regulation of ion pumps and other transport proteins, insulin-mediated regulation of glucose metabolism and the role of signal transduction networks in cell transformation. At Tufts University in the 1980s, Lewis and his collaborators unveiled and characterized the phosphoinositide 3-kinase (PI3K) signaling pathway; a discovery that revolutionized the field of lipid signaling. In this interview, he documents his journey from serendipitous discovery of the pathway to determining its diverse physiological functions and role in cancer – an incredible odyssey that has laid the groundwork for clinical trials based on PI3K inhibitors. He also discusses the impact his early life had in spurring a thirst to understand biological processes at the molecular level, highlights how his multiple collaborations have helped in translating his basic discoveries to the clinic and explains why eating a high-sugar diet can be harmful. Ongoing studies in the Cantley lab are aimed at determining the mechanistic underpinnings of pancreatic, colorectal, ovarian and breast cancers, particularly the role of cellular metabolic pathways. The group has recently shown, amongst other breakthroughs, that vitamin C could provide a promising therapy for certain hard-to-treat cancers., Summary: We spoke to Lewis Cantley about his career path and the story behind some of his key breakthroughs, including discovery of the phosphoinositide 3-kinase signaling pathway and insights into the role of dysregulated metabolism in cancer.

Katalin Susztak is currently Associate Professor at Perelman School of Medicine at the University of Pennsylvania, where she conducts research on chronic and diabetic kidney disease. After her medical studies, her science career began by investigating ion-channel regulation and function at Semmelweis University, in Budapest. She then moved to the United States, where, thanks to the fortunate encounter with her future mentor, Erwin Böttinger, she worked as a research fellow in the Renal Division of the Albert Einstein College of Medicine in New York. Since then, she has successfully kept pursuing her career in the field of kidney research. The innovative approach of Katalin’s lab is to combine efficient high-throughput analysis of patient samples with mechanistic approaches in animal models, in order to advance our understanding of kidney disease mechanisms and identify new therapeutic targets. In this interview, Katalin travels through her career, from her first steps into biophysics, to her residency and finally to her established position as a kidney-specialist scientist, discussing exciting aspects of her work and current challenges in her field.

Anne O’Garra is Head of the Division of Immunoregulation at the MRC National Institute for Medical Research (NIMR) in Mill Hill, London. In this interview, she recounts the excitement of her early career discoveries on cytokines and T-cell differentiation, and discusses progress on tuberculosis research by her group and multiple collaborators.