Cells have many paths to choose from in facing their demise.
Apoptosis, necroptosis, pyroptosis, ferroptosis… the list is ever-increasing as we dig deeper into the mysteries of cell death. All of these “-optosies” represent distinct journeys towards the grave, which are embarked upon under different circumstances, with unique impacts to surrounding cells and tissues. From normal developmental processes to inflammation, autoimmunity and many other contexts, these pathways are central to both health and disease.
Many essential life functions rely on cell death pathways, including fetal development, immunity, and wound healing. When these pathways malfunction, a multitude of diseases result– most notably cancer, but inflammatory diseases like atherosclerosis, rheumatoid arthritis, and Alzheimer’s Disease are also major players. Therefore, researching the proper functions of these cell death pathways, and what happens when they go awry, is critical to advance medical knowledge and treatments. Indeed, many therapeutic opportunities have arisen out of this field already, and many more are to come as we learn how to usher cells down the right path towards death.
At the upcoming “Why So Many Ways to Die?” meeting global research leaders across academic, clinical and industry sectors will convene in São Paulo, Brazil, to explore these many modes of cell death, from molecular to clinical perspectives.
Keynote Speaker Dr. Kim Newton from Genentech will kick-off the program, revealing new discoveries and research directions for the role of cell death pathways in inflammatory disease.
In this Q&A, Dr. Newton gives us a glimpse into her upcoming Keynote Address, and what she is looking forward to in Brazil.
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Q&A on Cell Death with Kim Newton
How does your work at Genentech bridge the basic and translational/clinical sides of cell death research?
Dr. Newton: Our main focus is to better understand the signaling mechanisms that regulate and underpin pro-inflammatory cell death.
The goal is to identify novel strategies for inhibiting this cell death, because this may benefit diseases with a prominent inflammatory component, such as atherosclerosis, inflammatory bowel disease, rheumatoid arthritis, and Alzheimer’s disease.
Inhibiting the kinase RIPK1, for example, has shown great promise in some disease models in mice. Such results inspire further collaboration with our medicinal chemistry and translational colleagues.
What are the medical implications and goals for this work?
Dr. Newton: The goal is to provide a new dimension to the armamentarium presently used to treat inflammatory pathologies. It is only through the discovery of innovative medicines that make a meaningful impact on the lives of patients that we will fulfill our mission.
How important is cross-disciplinary science to your research? What collaborators are you working with?
Dr. Newton: Collaborations are a big part of the science that we do. I’m fortunate to be able to draw on the knowledge of many expert colleagues for the questions that we seek to answer. If you look at the author’s affiliations on our papers, you’ll quickly appreciate that people from multiple departments and disciplines have come together to work on these projects.
How do you expect this meeting in Brazil will advance your work, and the field of Cell Death Research?
Dr. Newton: We all come to the meeting with slightly different perspectives and expertise, so it is a great opportunity to brainstorm together the challenging questions in the field. Informal discussions in the breaks between talks, at the poster sessions, and at mealtimes can stimulate new ideas and directions. Such discourse also conveys the excitement in the field to our younger colleagues, the graduate students, and postdoctoral fellows.Where do you think the field is headed? What speakers, topics, and new directions are you excited to hear of?
Where do you think the field is headed? What speakers, topics, and new directions are you excited to hear of?
Dr. Newton: I am fascinated by the increasingly complex layers of regulation that are being revealed in cell death signaling, and how the different “nuts and bolts” that make up the cell death machinery execute their functions. I am also drawn to studies that explore the relative contribution of apoptosis, necroptosis, and pyroptosis to pathogen defense or autoinflammatory conditions. Of course, it is always inspiring to learn how our understanding of cell death signaling is being exploited for the benefit of patients, as in the development of BCL-2 and MCL-1 inhibitors for the treatment of blood cancers.
How does this meeting stand out from other cell death meetings?
Dr. Newton: I think this meeting provides the best opportunity for experts from all parts of the world to engage with our South American scientific counterparts. There is generally good representation from the hosting country, and we have an attendee make up that is distinct from meetings held elsewhere which can only help to infuse the field with fresh ideas. The substantial free time between sessions in such a warm, idyllic setting will also foster discussion and interactions.
Attendees can look forward to learning about cutting edge research and an opportunity to discuss their own work with experts in the field.
Can you give us a sneak peek into your Keynote Address? What topics and themes do you plan to cover?
Dr. Newton: My talk is about caspase-8, a protease that is particularly perplexing in that it is required for both life and death. While cells need it to die by the extrinsic apoptosis pathway, some cells also need it to prevent another, more inflammatory form of cell death called necroptosis. Our genetic and biochemical studies have provided insights into how caspase-8 co-ordinates these activities, and, as often happens, also provided us with some new puzzles to solve. The take-home message will be:
The pathways to death are plastic and, under the appropriate circumstances, will rewire to drive death-induced inflammation. This process may contribute to the recalcitrance of certain chronic inflammatory pathologies to present day therapies.
What are your goals for “kicking off” the meeting? What do you hope the audience will take-away from your presentation?
Dr. Newton: The goal is to encourage discussion by presenting not only the answers to some burning questions but also the unexpected and surprising results and what they could mean for disease and pathogen defense. Our work definitely raises more questions than it answers, and addressing the right questions going forward will be the key to progress.
What is your favorite “way to die” and why?
Dr. Newton: Apoptosis because it’s less messy.
See Dr. Newton’s Keynote Address in Sao Paulo on November 19th at “Why So Many Ways to Die? Apoptosis, Necroptosis, Pyroptosis and Beyond“
Kim Newton earned her PhD from the University of Melbourne, Australia for her work with Dr. Andreas Strasser defining the role of death receptor signaling components, in particular FADD, in the proliferation and death of T-cells. She then moved to Genentech in South San Francisco, USA to complete postdoctoral work in the laboratory of Dr. Vishva Dixit. She is now a Senior Scientist at Genentech leading a group that seeks to understand the signaling mechanisms unleashing proinflammatory cell death programs during disease.
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