Richard A. Young

Education

  • PhD, 1979, Yale University
  • BS, 1975, Biological Sciences, Indiana University

Research Summary

We use experimental and computational technologies to determine how signaling pathways, transcription factors, chromatin regulators and small RNAs regulate gene expression in healthy and diseased cells. Our interests range from the basic molecular mechanisms behind gene control to drug development for cancer and other diseases caused by gene misregulation.

Awards

  • National Academy of Medicine, Member, 2019
  • National Academy of Sciences, Member, 2012
Eliezer Calo

Education

  • PhD, 2011, MIT
  • BS, 2006, Chemistry, University of Puerto Rico-Río Piedras

Research Summary

We focus on the molecular entities controlling and coordinating RNA metabolism — that is, the compendium of processes that involve RNA, including protein synthesis, processing, modifications, export, translation and degradation. Our goal is to understand how different aspects of RNA metabolism are controlled to generate structure and function during development, as well as how mutations in components of the RNA metabolic program lead to congenital disorders and cancer.

David Housman

Education

  • PhD, 1971, Brandeis University
  • BS, 1966, Biology, Brandeis University

Research Summary

We use genetic approaches to identify the molecular basis of human disease pathology. More specifically, we develop strategies to combat three major disease areas: cancer, trinucleotide repeat disorders like Huntington’s disease, and cardiovascular disease.

Awards

  • National Academy of Medicine, Member, 1997
  • National Academy of Sciences, Member, 1994
Leonard P. Guarente

Education

  • PhD, 1978, Harvard University
  • SB, 1974, Biology, MIT

Research Summary

We combine comprehensive bioinformatics analyses with functional analyses of pathways and genes to study aging in humans and mice. We apply these approaches to identify the major pathways and genes involved in the aging of certain brain regions. We are also studying muscular dystrophy and muscle loss with aging. Ultimately, our findings may guide studies in other organs and lead to a systemic understanding of mammalian aging.

Awards

  • Miami Winter Symposium, Feodor Lynen Award, 2012
  • University of Toronto, Charles H. Best Lectureship and Award, 2011
  • Dart/NYU Biotechnology, Achievement Award, 2009
  • French Academie des Sciences, Elected, 2009
  • American Academy of Arts and Sciences, Fellow, 2004
Revealing an imperfect actor in plant biotechnology

Whitehead Institute researchers detect the chemical mistakes of a common herbicide-resistance enzyme, then successfully re-engineer it for enhanced precision.

Nicole Davis | Whitehead Institute
November 29, 2017

A research team led by MIT’s Whitehead Institute for Biomedical Research has harnessed metabolomic technologies to unravel the molecular activities of a key protein that enables plants to withstand a common herbicide.

Their findings reveal how the protein — a kind of catalyst or enzyme first isolated in bacteria and introduced into plants such as corn and soybeans in the 1990s — can sometimes act imprecisely, and how it can be successfully re-engineered to be more precise. The new study, which appears online in the journal Nature Plants, raises the standards for bioengineering in the 21st century.

“Our work underscores a critical aspect of bioengineering that we are now becoming technically able to address,” says senior author Jing-Ke Weng, a member of the Whitehead Institute and an assistant professor of biology at MIT. “We know that enzymes can behave indiscriminately. Now, we have the scientific capabilities to detect their molecular side effects, and we can leverage those insights to design smarter enzymes with enhanced specificity.”

Plants provide an extraordinary model for scientists to study how metabolism changes over time. Because they cannot escape from predators or search for new food sources when supplies run low, plants must often grapple with an array of environmental insults using what is readily available — their own internal biochemistry.

“Although they appear to be stationary, plants have rapidly evolving metabolic systems,” Weng explains. “Now, we can gain an unprecedented view of these changes because of cutting-edge techniques like metabolomics, allowing us to analyze metabolites and other biochemicals on a broad scale.”

Key players in this evolutionary process, and a major focus of research in Weng’s laboratory, are enzymes. Traditionally, these naturally occurring catalysts have been viewed as mini-machines, taking the proper starting material (or substrate) and flawlessly converting it to the correct product. But Weng and other scientists now recognize that they make mistakes, often by latching on to an unintended substrate.

“This concept, known as enzyme promiscuity, has a variety of implications, both in enzyme evolution and more broadly, in human disease,” Weng says.

It also has implications for bioengineering, as Bastien Christ, a postdoctoral fellow in Weng’s laboratory, and his colleagues recently discovered.

Christ, then a graduate student in Stefan Hörtensteiner’s lab at the University of Zurich in Switzerland, was studying a particular strain of the flowering plant Arabidopsis thaliana as part of a separate project when he made a puzzling observation. He found that two biochemical compounds were present at unusually high levels in the plant’s leaves.

Strangely, these compounds (called acetyl-aminoadipate and acetyl-tryptophan) weren’t present in any of the normal, so-called wild type plants. As he and his colleagues searched for an explanation, they narrowed in on the source: an enzyme, called BAR, that was engineered into the plants as a kind of chemical beacon, enabling scientists to more readily study them.

But BAR is more than just a tool for scientists. It is also one of the most commonly deployed traits in genetically modified crops such as soybeans, corn, and cotton, enabling them to withstand a widely-used herbicide (known as phosphinothricin or glufosinate).

For decades, scientists have known that BAR, originally isolated from bacteria, can render the herbicide inactive by tacking on a short string of chemicals, made of two carbons and one oxygen (also called an acetyl group). As the researchers describe in their Nature Plants paper, BAR has a promiscuous side, and can work on other substrates, too, such as the amino acids tryptophan and aminoadipate (a lysine derivative).

That explains why they can detect the unintended products (acetyl-tryptophan and acetyl-aminoadipate) in crops genetically engineered to carry BAR, such as soybeans and canola.

Their research included detailed studies of the BAR protein, including crystal structures of the protein bound to its substrates. This provided them with a blueprint for how to strategically modify BAR to make it less promiscuous, and favor only the herbicide as a substrate and not the amino acids. Christ and his colleagues created several versions that lack the non-specific activity of the original BAR protein.

“These are natural catalysts, so when we borrow them from an organism and put them into another, they may not necessarily be perfect for our purposes,” Christ says. “Gathering this kind of fundamental knowledge about how enzymes work and how their structure influences function can teach us how to select the best tools for bioengineering.”

There are other important lessons, too. When the BAR trait was first evaluated by the U.S. Food and Drug Administration (FDA) in 1995 for use in canola, and in subsequent years for other crops, metabolomics was largely non-existent as a technology for biomedical research. Therefore, it could not be applied toward the characterization of genetically engineered plants and foods, as part of their regulatory review. Nevertheless, acetyl-aminoadipate and acetyl-tryptophan, which are normally present in humans, have been reviewed by the FDA and are safe for human and animal consumption.

Weng and his colleagues believe their study makes a strong case for considering metabolomics analyses as part of the review process for future genetically engineered crops.

“This is a cautionary tale,” Weng says.

The work was supported by the Swiss National Science Foundation, the EU-funded Plant Fellows program, the Pew Scholar Program in the Biomedical Sciences, and the Searle Scholars Program.

Stefani Spranger

Education

  • PhD, 2011, Ludwig-Maximilian University Munich/Helmholtz-Zentrum Munich
  • MSc, Biology, 2008, Ludwig-Maximilian University Munich/Helmholtz-Zentrum Munich
  • BSc, Biology, 2005, Ludwig-Maximilian University Munich/Helmholtz-Zentrum Munich

Research Summary

We examine the interaction between cancer and immune cells. Using tumor mouse models designed to mimic tumor progression in humans, we investigate the co-evolution of the anti-tumor immune response and cancer. Understanding the interplay between tumor cells and immune cells will help develop and improve effective cancer immunotherapies.

Awards

  • Forbeck Fellow, 2015
Jianzhu Chen

Education

  • PhD, 1990, Stanford University
  • BS, 1982, Biology, Wuhan University

Research Summary 

We seek to understand the immune system and its application in cancer immunotherapy and vaccine development. We study the molecular and cellular mechanisms behind immunological and disease processes, leveraging the vast array of genomic data, humanized mice and clinical samples.

Awards

  • American Association for the Advancement of Science, Fellow, 2012
Eric S. Lander

Education

  • PhD, 1981, Oxford University
  • AB, 1978, Mathematics, Princeton University

Research Summary

Following the successful completion of the Human Genome Project, the challenge now is to decipher the information encoded within the human genetic code — including genes, regulatory controls and cellular circuitry. Such understanding is fundamental to the study of physiology in both health and disease. At the Broad Institute, my lab collaborates with other to discover and understand the genes responsible for rare genetic diseases, common diseases, and cancer; the genetic variation and evolution of the human genome; the basis of gene regulation via enhancers, long non-coding RNAs, and three-dimensional folding of the genome; the developmental trajectories of cellular differentiation; and the history of the human population.

Awards

  • William Allan Award, American Society of Human Genetics, 2018
  • James R. Killian Jr. Faculty Achievement Award, MIT, 2016
  • Block Memorial Award for Distinguished Achievement in Cancer Research, Ohio State University, 2013
  • AAAS Philip Hauge Abelson Prize, 2015
  • Breakthrough Prize in Life Sciences, 2013
  • Harvey Prize for Human Health, Technion University, Israel, 2012
  • Dan David Prize, 2012
  • Albany Prize in Medicine and Biomedical Research, Albany Medical College, 2010
  • Gairdner Foundation International Award, Canada, 2002
  • Max Delbruck Medal, Berlin, 2001
  • MacArthur Foundation, MacArthur Fellowship, 1987
Harvey F. Lodish

Education

  • PhD, 1966, Rockefeller University
  • BS, 1962, Chemistry and Mathematics, Kenyon College

Research Summary

Harvey Lodish has been a leader in molecular cell biology as well as a biotechnology entrepreneur for over five decades. Much of his early research focused on the regulation of messenger RNA translation and the biogenesis of plasma membrane glycoproteins. Beginning in the 1980s, his research focused on cloning and characterizing many proteins, microRNAs, and long noncoding RNAs important for red cell development and function. His laboratory was the first to clone and sequence mRNAs encoding many hormone receptors, mammalian glucose transport proteins, and proteins important for adipose cell formation and function. He went on to identify and characterize several genes and proteins involved in insulin resistance and stress responses in adipose cells. Over the years, he has mentored hundreds of undergraduates, PhD and MD/PhD students, and postdoctoral fellows, and continues to teach award-winning undergraduate and graduate classes on biotechnology.

Harvey Lodish closed his lab in 2020 and is no longer accepting students.

Awards

  • Wallace H. Coulter Award for Lifetime Achievement in Hematology, American Society of Hematology, 2021
  • Donald Metcalf Award, International Society for Experimental Hematology, 2020
  • American Society for Cell Biology WICB Sandra K. Masur Senior Leadership Award, 2017
  • Pioneer Award, Diamond Blackfan Anemia Foundation, 2016
  • Mentor Award in Basic Science, American Society of Hematology, 2010
  • President, American Society for Cell Biology, 2004
  • Associate Member, European Molecular Biology Organization (EMBO), 1996
  • National Academy of Sciences, Member, 1987
  • American Academy of Arts and Sciences, Fellow, 1986
  • John Simon Guggenheim Memorial Foundation, Guggenheim Fellowship, 1977
Rudolf Jaenisch

Education

  • MD, 1967, University of Munich

Research Summary

We aim to understand the epigenetic regulation of gene expression in mammalian development and disease. Embryonic stem cells are important because they have the potential to generate any cell type in the body and, therefore, have great potential for regenerative medicine. We study the way somatic cells reprogram to an embryonic pluripotent state, and use patient specific pluripotent cells to study complex human diseases.

Awards

  • German Society for Biochemistry and Molecular Biology, Otto Warburg Medal, 2014
  • New York Academy, Medicine Medal, 2013
  • Franklin Institute, Benjamin Franklin Medal, 2013
  • National Science Foundation, National Medal of Science, 2011
  • National Science Foundation, National Medal of Science, 2010
  • National Academy of Sciences, Member, 2003