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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.

Harold Varmus has made pioneering contributions to our understanding of cancer as a genetic disease. The discovery of the cellular origin of retroviral oncogenes earned him and his long-term collaborator, Michael Bishop, the Lasker Prize for Basic Medical Sciences in 1982 and the Nobel Prize in Physiology and Medicine in 1989. Throughout his career, Varmus has held several leadership roles that shaped science policy in the US and worldwide, and he has been an outspoken advocate for open science. In this interview, he talks (among other things) about the factors that shaped his early career choices, the thrill of scientific discovery, and the importance of including diverse populations in genomic studies of cancer and other diseases.

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.

Gerald (Gerry) Rubin, pioneer in Drosophila genetics, is Founding Director of the HHMI-funded Janelia Research Campus. In this interview, Gerry recounts key events and collaborations that have shaped his unique approach to scientific exploration, decision-making, management and mentorship – an approach that forms the cornerstone of the model adopted at Janelia to tackle problems in interdisciplinary biomedical research. Gerry describes his remarkable journey from newcomer to internationally renowned leader in the fly field, highlighting his contributions to the tools and resources that have helped establish Drosophila as an important model in translational research. Describing himself as a ‘tool builder’, his current focus is on developing approaches for in-depth study of the fly nervous system, in order to understand key principles in neurobiology. Gerry was interviewed by Ross Cagan, Senior Editor of Disease Models & Mechanisms., Drosophila Collection: Ross Cagan spoke to Gerry Rubin about his career path and the story behind some of his key breakthroughs, as well as his unique and successful approach to management and mentorship.

Luke O'Neill is professor of biochemistry in the School of Biochemistry and Immunology at Trinity College Dublin, and his main research focus is innate immunity and its key output, inflammation. His work has explored the key sensors and mediators of infection, including the Toll-like receptors, inflammasomes and cytokines in the interleukin-1 (IL-1) family. Luke received the Royal Irish Academy Gold Medal for Life Sciences in 2012 and the European Federation of Immunology Societies Medal in 2014. He was elected a member of the European Molecular Biology Organisation (EMBO) in 2005 and a Fellow of the Royal Society in 2016. In this interview, Luke talks about the necessary collaboration between immunologists and cancer scientists, inflammaging, and his rock-star alter-ego as frontman of The Metabollix.

Karen Vousden is an internationally renowned cancer scientist whose contributions to solving the p53 puzzle are changing the way we think about this important tumour suppressor. She has been honoured with many prizes and elected memberships throughout her career, and was appointed Commander of the Order of the British Empire (CBE) in 2010 and Foreign Associate of the US National Academy of Sciences in May 2018. Karen is an approachable and diligent scientist, a respected mentor and an inspirational role model. She is currently a group leader at the Francis Crick Institute in London and Chief Scientist at Cancer Research UK (CRUK). In this interview, Karen talks about the mentors that inspired her, the discoveries that brought about her interest in cancer metabolism, and her interests outside the lab. Karen Vousden's research focuses on the many functions of p53 in cancer and beyond. Her scientific journey in the field of genetics started with undergraduate and graduate work on transfer RNA (tRNA) suppression with Lorna Casselton at the University of London, UK. She studied Ras and viral oncogenes during her postdoctoral training with Christopher Marshall and Douglas Lowy. The interactions between viral oncogenes and mammalian tumour suppressors drew her into the field of p53. Her group (in parallel with others) discovered the p53 targets PUMA and TIGAR, the latter of which spurred her interest in cancer metabolism.

Howard Jacob is best known for pioneering genomic sequencing of a patient to solve a mysterious pediatric case in 2010. With roots in pharmacology and cardiovascular disease, however, his career has largely been dedicated to dissecting the physiology and genetics of the rat to help understand complex human diseases. Howard was Director of the Human and Molecular Genetics Center at the Medical College of Wisconsin for 16 years, during which time he applied a combination of approaches, including quantitative genetics, integrative physiology and next-generation sequencing, in rat models to shed light on cardiovascular, metabolic and renal disorders. He was a key contributor to the genomic toolbox for rat research, and generated the first targeted-knockout rat models using zinc-finger-nuclease technology. He also contributed to sequencing of the rat genome and establishment of the Rat Genome Database. In this interview, Howard provides his perspectives on the past, present and future of rat-based translational research and explains why, despite his many successes as the leader of a rat group, he recently made the transition to clinical genomics., Summary: Howard Jacob describes some of the key moments and breakthroughs in his remarkable career, and the path that led him from his research roots in cardiovascular disease and rat physiology to becoming Director of a clinical genomic sequencing program.

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.

Geoffrey W. Smith is currently the Managing Director of Mars Ventures. He actually started his studies with a Bachelor of Arts degree and a Doctorate in Law but then, in part by chance and in part by following in his family footsteps, he stepped into the healthcare and biotech field. Since then, he has successfully contributed to the birth of a number of healthcare companies and has also held academic positions at the Icahn School of Medicine at Mount Sinai and at The Rockefeller University in New York, teaching about the interface between science and business. During 2014 he served as Senior Editor on Disease Models & Mechanisms, bringing to the editorial team his valuable experience in drug development and discovery. In this interview, Geoff talks to Ross Cagan, Editor-in-Chief of Disease Models & Mechanisms, about how he developed his incredibly varied career, sharing his views about industry, academia and science publishing, and discussing how academia and industry can fruitfully meet to advance bioscience, train the scientists and stakeholders of the future, and drive the successful discovery of new therapeutics to treat human disease.

David Rubinsztein is currently professor of Molecular Neurogenetics at the University of Cambridge, UK and Wellcome Trust Principal Research Fellow. He is based in the Cambridge Institute for Medical Research, where he is currently the Deputy Director. He started his studies in medicine in Cape Town, South Africa, and was initially interested in both clinical and research work. During his PhD, he discovered himself truly passionate about cell biology and genetics of disease and moved to Cambridge, where he specialised in Genetic Pathology, after which he received a 6-year Glaxo-Wellcome Fellowship to investigate mechanisms of protein misfolding and aggregation in Huntington's disease and other proteinopathies. Since then, he has been committed to lab research and has been a leading scientist in elucidating the roles of autophagy in neurodegeneration. In his lab, he combines cell biology tools with animal studies to elucidate the potential of autophagy manipulation as a strategy to eliminate toxic misfolded and aggregated proteins and treat neurodegenerative diseases. He has been recently appointed as academic lead PI for the Alzheimer's Research UK Drug Discovery Institute in Cambridge, whose goal is to develop disease-modifying treatments for neurodegenerative diseases. In this interview, David tells us how he developed his career as an independent scientist, sharing his experience and views about the scientific progress in our understanding of neurodegenerative diseases and in developing potential therapeutics.

Sabine Cordes is currently Senior Investigator at the Lunenfeld-Tanenbaum Research Institute, where she studies the genes involved in craniofacial and neuronal development and psychiatric disorders. Although now renowned as an excellent mouse geneticist and neurobiologist, she is actually a biochemist by training. Indeed, she started her career at the Department of Biochemistry at Berkeley, University of California, studying ethylene-induced gene expression during tomato fruit ripening with Robert L. Fischer. She then became fascinated by brain development and decided to join Greg Barsh’s lab at Stanford University to work specifically on hindbrain segmentation. Her interest in psychiatric disorders was, in her own words, ‘accidental’. In this interview, Sabine recounts the interesting steps that took her from the study of chemistry and molecules to that of genes and mouse genetics, to researching on neurodevelopment and mood disorders. She also shares with us her personal forward-looking view of biomedical science, based on her own experience and on the impact of new advances that are revolutionising our understanding of cell biology and neurobiology.

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.

Leonard Zon, who is based at Harvard Medical School, is internationally recognized for his pioneering work in hematology and stem cell biology. His lab uses zebrafish as a model to understand blood cell development and, in recent years, has made inspiring breakthroughs in the treatment of blood diseases and cancer, helping to establish zebrafish as a powerful model for translational research. In this interview, Leonard speaks to Disease Models & Mechanisms Editor-in-Chief, Ross Cagan, about the evolution of his career from developmental biologist to physician-scientist and the stories behind some of his major research accomplishments. He also discusses challenges and opportunities in zebrafish research and provides advice on translating basic research findings to the clinic.

The Bohmann lab, based at the University of Rochester Medical Center in New York, uses Drosophila to explore the cross-talk between stress and metabolic regulation, with the goal of understanding how the signaling pathways involved can drive aging, cancer and other degenerative pathologies. In this interview, Dirk Bohmann describes his motives for moving into the fly field, explains how the study of aging can give important insights into complex disease mechanisms, and advocates using a systems-biology approach to advance drug discovery.

Kym Boycott is currently a Clinical Geneticist at the Children's Hospital of Eastern Ontario (CHEO) and a Senior Scientist at the CHEO Research Institute, in Canada, where she tries to better understand mechanisms of rare genetic diseases and improve the management of pediatric patients with these conditions. Her interest in Medical Genetics dates back to her undergraduate studies at Queen's University in Kingston, when she was captured by Dr Patrick MacLeod's lectures on this subject. Thus, she embarked on a PhD in Medical Genetics and joined Dr Torben Bech-Hansen's lab at the University of Calgary, where she investigated the cause of a rare genetic form of vision loss. After completion of her PhD, she attended the medical school program at the University of Calgary and obtained her MD in 2005. Having both a PhD and MD allowed her to have a translational perspective from the beginning of her career. At CHEO, Kym and her group aim to bridge basic and clinical knowledge to quickly diagnose – by using next-generation sequencing – and improve the management of rare diseases, also known as orphan diseases. Kym is co-leader of the Canadian Rare Diseases Models and Mechanisms (RDMM) project, the goal of which is to connect basic scientists who work with animal models to clinician investigators studying rare diseases, thereby catalyzing investigation of disease mechanism and in some instances facilitating therapeutic configuration for rare diseases. In this interview, Kym shares with us her unique experience and expertise, fighting on the front line against rare diseases.

Rick Morimoto Director of the Rice Institute of Biomedical Research and the Bill and Gayle Cook Professor of Biology at Northwestern University, is renowned for his insights into the heat shock response and its role in protein-folding diseases and aging. As part of Disease Models & Mechanisms’ (DMM’s) special series on protein-folding diseases, Rick recalls the karmic events that influenced his career and discusses the importance of invertebrate model systems to reveal the basic mechanisms underlying aging and protein misfolding, as well as efforts to discover therapies to reverse these biological processes.

Liz Patton is a Senior Lecturer at the MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, where she leads a research group whose goal is to understand melanocyte and melanoma development. Early on in her research career, Liz investigated cell cycle regulation in yeast and the implications for cancer, but now primarily exploits the zebrafish model to identify new pathways and therapeutic compounds relevant to melanoma. In this interview, Liz recalls some of her most exciting breakthroughs to date, discusses the advantages of zebrafish as a disease model and provides her perspectives on the current challenges in cancer research.

Hans Clevers, Professor of Molecular Genetics at Utrecht University, began his career in immunology and developmental biology, but a shift towards intestinal research in the late 1990s led to his group’s pioneering discovery that Lgr5 is a marker of tissue stem cells – a finding that paved the way for a cascade of key insights into the molecular signalling pathways that are dysregulated in cancer. Interviewed here by Ross Cagan, Editor-in-Chief of Disease Models & Mechanisms, Hans recalls the mentors and discoveries that motivated his transition from basic to applied science, discusses his style of lab management and mentorship, and highlights the potential of organoid-based therapy for personalised medicine.

Neal Copeland and Nancy Jenkins – partners in the lab and in life – are world leaders in cancer research, mouse genetics and developmental genetics. In this interview, they recall the adventure of their joint career and discuss their views on current challenges in cancer research.

Jeffrey Friedman is a molecular geneticist whose group, in 1994, reported the long-sought identity and function of leptin (Zhang et al., 1994), a key fat-derived hormone that regulates feeding behaviour and body weight. This represented a massive step forward in our understanding of obesity, which is now one of the world’s fastest-growing health problems. Here, he recalls his journey of discovery and offers his perspective on the future of obesity research.

Martin Raff is an Emeritus Professor at University College London (UCL), where he worked for more than 30 years on various aspects of immunology, cell biology and neurobiology until his retirement in 2002. In this interview, he recounts the thrill of his first few years in science, and discusses his current fascination with the fast-moving field of neuropsychiatric disorders.

Professor Steve O’Rahilly is one of the UK’s most renowned clinical researchers. He made his reputation by combining clinical practice with scientific and clinical studies focused on understanding the causes and consequences of obesity and insulin resistance. Here, he talks about his research philosophy, and his wider role as a spokesman for obesity research.

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.

George Tidmarsh, new Senior Editor on Disease Models & Mechanisms (DMM), is a physician with an academic science and medicine background and over two decades of industry experience at the cutting edge of biotechnology and drug development. Currently CEO of La Jolla Pharmaceutical Company Inc. as well as Consulting Associate Professor at Stanford University School of Medicine, he provides an insight into the value of industry as a conduit between academic research and patient benefit.

Ross Cagan, new Editor-in-Chief of Disease Models & Mechanisms (DMM), is a developmental and translational biology researcher with expertise in using fruit fly models. Based at the Icahn School of Medicine at Mount Sinai, he holds professorships in Developmental and Regenerative Biology, Oncological Sciences and Ophthalmology. He is also Associate Dean of the Graduate School for Biological Sciences and co-founder of Medros, Inc. In this interview, he recalls the events and mentors that helped shape his career, explains why he loves flies, and outlines his vision for DMM.

Monica Justice, a recently appointed Senior Editor on Disease Models & Mechanisms (DMM), is Professor in the Department of Molecular and Human Genetics at Baylor College of Medicine (BCM). She leads several research teams that are merging mouse modeling with clinical genetics to elicit new information on disease mechanisms and to develop potential treatment strategies, with a focus on hematopoietic cancers and genetic syndromes. In this interview, Monica discusses what led her to focus on molecular, developmental and translational biology; her current work and future goals; and the reality of creating a balance between a demanding research role and life beyond the lab.

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.

Mark Fishman has served as President of the Novartis Institutes for BioMedical Research (NIBR) since 2002, and in a former academic role was among the first to develop the zebrafish system for studying development and disease. Here, he recalls what it was like to ride the first real wave of zebrafish research, discusses industry-academia collaborations and provides a current perspective on drug development.

Laurie Glimcher is a physician-scientist with a true passion for research. In this interview, she discusses her early career, key issues in successful clinical translation and her move to become Dean of Weill Cornell Medical College in Manhattan.

Joan Brugge has been an innovator in cancer research since the beginning of her career, when she isolated the viral and cellular forms of the Src protein as a postdoctoral fellow at the University of Colorado. In this interview, she describes the exciting sequence of events that opened up the field during this time, and discusses why a career in cancer research is still such an inspiring path to follow today.

Irv Weissman has pursued many areas of biomedical research throughout his prolific career as a medical doctor and researcher. In this interview, he recalls his early years studying immunology in mice, and discusses the more recent challenges he has faced when attempting to develop stem-cell-based therapies with industry.

Professor Frances Balkwill of Barts Cancer Institute, Queen Mary, University of London, is driven by two passions: translating basic cancer research into new patient therapies and encouraging science literacy in children through a range of communication-based activities. In this interview, she discusses current challenges in translational cancer research and how the two arms of her career inspire one another.

Ruslan Medzhitov was inspired to become a researcher in immunology on reading a 1989 paper written by Charles Janeway that outlined a new theory for immune system activation. Just a few years later, having achieved a postdoc position in Janeway’s lab, he carried out the experiments that confirmed the theory, re-igniting interest in the field of innate immunity and launching his own career. Here, he discusses this early discovery and explains what he considers the three most important questions facing immunologists today.

Nancy Hopkins is famous for pushing the envelope: both in her pursuit to understand cancer genetics and in exposing professional disparities between men and women. Here, she discusses influential moments that have defined her career path, and her concerns for the future.

Sir Paul Nurse is a recipient of the 2001 Nobel Prize in Medicine for his work on one of the key regulators of the cell cycle, CDK (cyclin-dependent kinase). In this interview with Jim Smith, he discusses his choice of model organism, scientific leadership and the early influences on his career.

Sir John Gurdon used nuclear transplantation and cloning to show that the nucleus of a differentiated somatic cell retains the totipotency necessary to form a whole organism. Here, he discusses model organisms, the future implications for his early work on medicine and his thoughts about scientific publishing.

Susan Lindquist is a founding editor of DMM, whose pioneering work in yeast has advanced our understanding of protein folding in disease, including Parkinson’s, Huntington’s and prion diseases. Here, she discusses her personal approach to model organism research and scientific leadership.

Mario Capecchi recently won the Nobel Prize for contributions to genetics that have catapulted the mouse to the status of the most valuable of all animal models. He has a personal story that is as rich and interesting as his science. Here, he discusses the journey that led him to gene targeting and his vision for the future.

Gerard Evan is a founding editor of DMM, whose work uncovered a crucial role for the tumor suppressor Myc in cellular apoptosis. Here, he talks about the future of cancer therapy and the responsibility of academic science in tackling these complex questions.