About this Video
The two diseases most likely to afflict us as we age – cancer and neurodegenerative diseases like Alzheimer’s – may both have an Achilles’ heel. David Pincus will argue that the two are fundamentally linked by the vital cellular process of “protein folding”. This provocative talk posits that protein folding is the key to unlocking all cancers – not just for treating specific cancers, like breast cancer or lung cancer – and for all neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.
David Pincus, a Fellow at the Whitehead Institute and recipient of the NIH Director’s Early Independence Award, is a molecular and cell biologist given the rare opportunity to direct an independent research laboratory and pursue his scientific ideas immediately following completion of his PhD. His studies on how cells respond to stress point to an underlying connection between cancer and neurodegenerative diseases that he hopes to exploit through research to potentially solve both.
About the Speaker
David Pincus is a fellow at the Whitehead Institute at MIT, working to reveal the underlying mechanisms cells employ to maintain homeostasis in inherently fluctuating environments. Any change in the surroundings – be it a change in temperature, pH, the amount of salt, the availability of nutrients, etc. – is an excursion away from equilibrium and a challenge to the cell. By understanding at the molecular level how cells sense and respond to these inevitable environmental fluctuations, they are striving to ascertain the limits that healthy cells can cope with, the pathways responsible for coping, and how these pathways can break down or be hijacked in various disease states such as diabetes and cancer.
The goal of their efforts is to define common control strategies that cells employ to regulate their activities when faced with environmental perturbations. To approach the problem experimentally, they use the budding yeast Saccharomyces cerevisiae as a model organism to interrogate signaling in stress response pathways, using the regulation of the highly conserved Heat Shock Factor (HSF) as an initial test bed. They aim to answer the following questions: 1) What is the relationship between expression level of HSF and its activity? 2) How does phosphorylation of HSF contribute to HSF activity? 3) How do interactions with chaperone proteins regulate HSF? 4) How do expression level, phosphorylation and chaperone protein interactions coordinate an appropriate response in real time to different perturbations?
By answering these questions – and in the process developing widely applicable approaches to paint quantitative and mechanistic portraits of stress adaptation – they strive to ascertain both specific instantiations as well as general principles that control cellular stress responses to maintain homeostasis and maximize fitness.
Pincus joined Whitehead Institute in the fall of 2012, having graduated with his PhD from University of California, San Francisco.