Michael B. Yaffe

Education

  • PhD, 1987, Case Western Reserve University; MD, 1989, Case Western Reserve University
  • BS, 1981, Chemistry with Concentration in Solid-State and Polymer Physics, Cornell University

Research Summary

Our goal is to understand how signaling pathways are integrated at the molecular and systems levels to control cellular responses. We have two main focuses: First, we study signaling pathways and networks that control cell cycle progression and DNA damage responses in cancer and cancer therapy. Second, we examine the cross-talk between inflammation, cytokine signaling and cancer. Much of our work focuses on how modular protein domains and kinases work together to build molecular signaling circuits, and how this information can be used to design synergistic drug combinations for the personalized treatment of human disease.

Awards

  • MacVicar Faculty Fellow, 2021
  • Fellow, Association of American Physicians, 2021
  • Teaching with Digital Technology Award, 2018
Amy E. Keating

Education

  • PhD, 1998, University of California, Los Angeles
  • SB, 1992, Physics, Harvard University

Research Summary

Our goal is to understand, at a high level of detail, how the interaction properties of proteins are encoded in their sequences and structures. We investigate protein-protein interactions by integrating data from high throughput assays, structural modeling, and bioinformatics with biochemical and biophysical experiments. Much of our work focuses on α-helical coiled-coil proteins, Bcl-2 apoptosis-regulating proteins, and protein domains that bind to short linear motifs.

Gene-Wei Li

Education

  • PhD, 2010, Harvard University
  • SB, 2004, Physics, National Tsinghua University

Research Summary

We seek to understand the optimization of bacterial proteomes at both mechanistic and systems levels. Our work combines high-precision assays, genome-wide measurements, and quantitative/biophysical modeling. Ongoing projects focus on the design principles of transcription, translation, and RNA maturation machineries in the face of competing cellular processes.

Awards

  • Smith Odyssey Award, 2020
  • MIT Committed to Caring Award, 2020
  • NSF Career Award, 2019
  • Pew Biomedical Scholar, 2017
  • Smith Family Award for Excellence in Biomedical Research, 2017
  • NIGMS R35 Maximizing Investigator Research Award, 2017
  • Sloan Research Fellowship, 2016
  • Searle Scholar, 2016
  • NIH Pathway to Independence Award, 2013
Peter Reddien

Education

  • PhD, 2002, MIT
  • SB, 1996, Molecular Biology, University of Texas at Austin

Research Summary

We investigate how stem cells are regulated to regenerate missing tissues. We study the cellular events involved in this process and the attendant roles for regulatory genes that control regeneration steps. We utilize an array of methodologies, including high-throughput sequencing, RNA interference (RNAi) screening, and numerous assays and tools for phenotypic analysis to characterize regeneration regulatory genes.

Awards

  • Howard Hughes Medical Institute, HHMI Investigator, 2013
David C. Page

Education

  • MD, 1984, Harvard Medical School
  • BS, 1978, Chemistry, Swarthmore College

Research Summary

We seek to understand the genetic differences between males and females — both within and beyond the reproductive tract. We study the medical ramifications of these differences in a broad context, through comparative biological, evolutionary, developmental and clinically focused analyses. Our three main veins of research relate to sex differences in health and disease, sex chromosome genomics, and germ cell origins and development.

Awards

  • American Academy of Arts and Sciences, Fellow, 2012
  • March of Dimes, Developmental Biology, 2011
  • National Academy of Medicine, Member, 2008
  • National Academy of Sciences, Member, 2005
  • Howard Hughes Medical Institute, HHMI Investigator, 1990
  • MacArthur Foundation, MacArthur Fellowship, 1986
Adam C. Martin

Education

  • PhD, 2006, University of California, Berkeley
  • BS, 2000, Biology and Genetics, Cornell University

Research Summary

We study how cells and tissues change shape during embryonic development, giving rise to different body parts. We visualize these changes to determine how mechanical forces drive massive tissue movements in the fruit fly, Drosophila melanogaster. In addition, we also study the regulation of tissue integrity, investigating the processes that regulate the epithelial-to-mesenchymal transition or EMT.

Joseph (Joey) Davis

Education

  • PhD, 2010, MIT
  • BA,  2003, Computer Science, University of California, Berkeley
  • BS, 2003, Biological Engineering, University of California, Berkeley

Research Summary

The Davis lab is working to uncover how cells construct and degrade complex molecular machines rapidly and efficiently. We apply a variety of biochemical, biophysical, and structural approaches including quantitative mass spectrometry and single particle cryo-electron microscopy to understand the detailed molecular mechanisms of these processes. Ongoing projects in the lab are focused on autophagy, an essential eukaryotic protein and organelle degradation pathway, and assembly of the ribosome, which is essential in all cells.

Awards

  • Sloan Research Fellowship, Alfred P. Sloan Foundation, 2021
  • National Institute on Aging R00 Fellowship, 2017
  • National Institute on Aging K99 Fellowship, 2015
Christopher Burge

Education

  • PhD, 1997, Stanford University
  • BS, 1990, Biological Sciences, Stanford University

Research Summary

We aim to understand the code for RNA splicing: how the precise locations of introns and splice sites are identified in primary transcripts and how its specificity changes in different cell types. Toward this end, we are mapping the RNA-binding affinity spectra of dozens of human RNA-binding proteins and integrating this information with in vivo binding and activity data.  We are also studying the functions of 3’ untranslated regions, including their roles in mRNA localization and microRNA regulation. The lab uses a combination of computational and experimental approaches to address these questions.

Awards

  • Schering-Plough Research Institute Award (ASBMB), 2007
  • Overton Prize for Computational Biology (ISCB), 2001
David Bartel

Education

  • PhD, 1993, Harvard University
  • BA, 1982, Biology, Goshen College

Research Summary

We study microRNAs and other small RNAs that specify the destruction and/or translational repression of mRNAs. We also study mRNAs, focusing on their untranslated regions and poly(A) tails, and how these regions recruit and mediate regulatory phenomena.

Awards

  • National Academy of Sciences, Member, 2011
  • Howard Hughes Medical Institute, HHMI Investigator, 2005
  • National Academy of Sciences Award in Molecular Biology, 2005
  • AAAS Newcomb Cleveland Prize, 2002
Muscle plays surprising role in tissue regeneration

Whitehead Institute researchers have pinpointed distinct muscle subsets that orchestrate and pattern regrowth.

Nicole Davis | Whitehead Institute
November 22, 2017

Researchers at the Whitehead Institute have illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration.

In a paper appearing online today in Nature, they reveal that a subtype of muscle fibers in flatworms is required for triggering the activity of genes that initiate the regeneration program. Notably, in the absence of these muscles, regeneration fails to proceed. Another type of muscle, they report, is required for giving regenerated tissue the proper pattern — for example, forming one head instead of two.

“One of the central mysteries in organ and tissue regeneration is: How do animals initiate all of the cellular and molecular steps that lead to regeneration?” says senior author Peter Reddien, a member of Whitehead Institute, professor of biology at MIT, and investigator with the Howard Hughes Medical Institute. “We’ve helped answer this question by revealing a surprising molecular program that operates within a subgroup of muscle cells that helps establish the molecular information required for proper tissue regeneration after injury.”

For more than a decade, Reddien and the researchers in his laboratory have studied the biological mechanisms that underlie regeneration in a tiny flatworm called planarians. These worms possess some impressive regenerative capabilities: When sliced in two, each piece of the worm can regrow the body parts needed to form two complete organisms. In previous studies, Reddien’s team identified a set of always-on genes, known as position control genes (PCGs), that provide cells with region-specific instructions, like a set of GPS coordinates, that tell cells where they are in the body, and thus what body part to regenerate. Interestingly, PGCs are active in planarian muscle cells, suggesting muscle may play a major role in the regeneration process.

“This discovery raised a lot of questions about how muscle participates in this process,” Reddien says.

In planarians, there are a handful of muscle cell types. For example, if you imagine the worms as simple cylindrical tubes, there are longitudinal muscle fibers, which run head-to-tail along the tubes’ long axis. There are also circular fibers, which are perpendicular to the longitudinal fibers and hug the tubes’ outer circumference.

To assess the roles of these different muscle cell types in regeneration, first author Lucila Scimone and her colleagues needed a method to selectively remove them. When myoD, a gene found specifically in the longitudinal fibers, is inhibited, those fibers fail to form. Similarly, the nkx1-1 gene marks the circular fibers, and when its function is reduced, they do not develop. Using these genes as molecular scalpels, Scimone and her co-authors could test the effects of ablating these distinct muscle groups on regeneration.

Surprisingly, when the longitudinal fibers were removed, the results were dramatic. The worms live quite normally, but when they are injured (the head removed, for example) they cannot regenerate the missing parts.

“This is an amazing result; it tells us that these longitudinal fibers are essential for orchestrating the regeneration program from the very beginning,” says Scimone, a scientist in Reddien’s lab.

As the researchers dug deeper into the finding, they learned that the functions of two critical genes are disrupted when longitudinal fibers are missing. These genes, called notum and follistatin, are known for their fundamental roles in regeneration, controlling head-versus-tail decisions and sustained cell proliferation, respectively, following tissue injury.

In addition to this essential role for longitudinal fibers, the research team also uncovered a key role for circular fibers. When these muscles are missing, planarians are able to regenerate missing body parts, but what regrows is abnormally patterned. For example, two heads may be regenerated within a single outgrowth, instead of one.

These results underscore an important and previously unappreciated role for muscle, widely known for its contractile properties, in instructing the tissue regeneration program. The Whitehead researchers will continue to probe the role of different muscle cell types in planarian regeneration and also explore whether other animals with regenerative capabilities possess a similar muscle-localized program for conferring positional information.

“It’s hard to understand what limits humans’ abilities to regenerate and repair wounds without first knowing what mechanisms are enabling some animals, like planarians, to do it so amazingly well,” Reddien says.

This work was supported by the National Institutes of Health, Howard Hughes Medical Institute, and the Eleanor Schwartz Charitable Foundation.