Research Area: Cell Biology

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.

Elly Nedivi

Education

  • PhD, 1991, Stanford University
  • BSc, 1982, Biology and Biochemistry, Hebrew University, Israel

Research Summary

The property of the brain that allows it to constantly adapt to change is termed plasticity, and is a prominent feature not only of learning and memory in the adult, but also of brain development. Connections between neurons (synapses) that are frequently used become stronger, while those that are unstimulated gradually dwindle away. The Nedivi lab works to identify the cellular mechanisms that underlie the addition and elimination of synaptic connections in response to activity using genetic and in vivo imaging approaches.

Awards

  • Elected Member at Large, AAAS, 2019-2023
  • Elected Member, Dana Alliance, 2019
  • BCS Award for Excellence in Undergraduate Teaching, 2018
  • American Association for the Advancement of Science (AAAS), Fellow, 2016
  • AFAR Julie Martin Mid-Career Award in Aging Research, 2007 – 2011
  • Edgerly Innovation Fund Award, 2006
  • Dean’s Education and Student Advising Award, 2003
  • NSF Powre Award, 1999
  • Alfred P . Sloan Research Fellowship, 1999 – 2001
  • Ellison Medical Foundation New Scholar Award, 1997 – 2002
Phillip A. Sharp

Education

  • PhD, 1969, University of Illinois, Urbana-Champaign
  • BA, 1966, Chemistry and Math, Union College

Research Summary

We investigate small, non-coding RNAs called microRNAs (miRNAs), which regulate over half of the genes in mammalian cells at the stages of translation and mRNA stability. We are also interested in the processes underlying transcription from the anti-sense strand (so-called “divergent” transcription), as well as the relationship between elongation of transcription, RNA splicing, and chromatin modifications.

Awards

  • AACR Award for Lifetime Achievement in Cancer Research, 2020
  • AACR Distinguished Award for Extraordinary Scientific Innovation and Exceptional Leadership in Cancer Research and Biomedical Science, 2018
  • Royal Society of London, Foreign Fellow, 2011
  • National Science Foundation, National Medal of Science, 2004
  • The Nobel Foundation, Nobel Prize in Physiology or Medicine, 1993
  • National Academy of Medicine, Member, 1991
  • American Association for the Advancement of Science, Fellow, 1987
  • American Academy of Arts and Sciences, Fellow, 1987
  • National Academy of Sciences, Member, 1983
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
Iain M. Cheeseman

Education

  • PhD, 2002, University of California, Berkeley
  • BS, 1997, Biology, Duke University

Research Summary 

Our lab is fascinated by the molecular machinery that directs core cellular processes, and in particular how these processes are modulated and rewired across different physiological contexts. Our work has focused on the proteins that direct chromosome segregation and cell division, including the macromolecular kinetochore structure that mediates chromosome-microtubule interactions. Although cell division is an essential cellular process, this machinery is remarkably flexible in its composition and properties, which can vary dramatically between species and are even modulated within the same organism — over the cell cycle, during development, and across diverse physiological situations. To define the basis by which the kinetochore and other core cellular structures are rewired to adapt to diverse situations and functional requirements, we are currently investigating diverse transcriptional, translational, and post-translational mechanisms that act to generate proteomic variability both within individual cells and across tissues, cell state, development, and disease.

Awards

  • Global Consortium for Reproductive Longevity and Equality (GCRLE) Scholar Award, 2020
  • MIT Undergraduate Research Opportunities Program (UROP) Outstanding Mentor – Faculty, 2019
  • American Society for Cell Biology (ASCB) Early Career Life Scientist Award, 2012
  • Searle Scholar Award, 2009-2012

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Troy Littleton

Education

  • PhD, 1994, Baylor College of Medicine; MD, 1997, Baylor College of Medicine
  • BS, 1989, Biochemistry, Louisiana State University

Research Summary

Using Drosophila, we study how neurons form synaptic connections, as well as how synapses transmit information and change during learning and memory. We also investigate how alterations in neuronal signaling underlie several neurological diseases, including epilepsy, autism, and Huntington’s Disease. We hope to bridge the gap between the molecular components of the synapse and the physiological responses they mediate.

Of highways, engines, and chromosomes

Whitehead researchers unravel fundamental molecular machinery that propels chromosome movement

November 16, 2017

Each day, billions of cells in the human body undergo a vital ritual, wherein one cell divides to form two. This process, known as cell division, is as beautiful as it is essential, undergirding the body’s growth in times of both health and disease. Despite the fact that cell division (or “mitosis”) has been a basic topic in high school biology classes for the past 70 years, the mechanisms by which cells conduct this critical event remain poorly understood. In particular, there are lingering uncertainties about how chromosomes — large units of DNA that include our genes — get properly allocated so that both daughter cells receive intact, complete copies of their genetic blueprint.

“People have been watching chromosomes move, align, and segregate for more than a century — it’s such a fundamental aspect of biology,” says Iain Cheeseman, a member of the Whitehead Institute for Biomedical Research and an associate professor of biology at Massachusetts Institute of Technology. “It’s also much more elegant and complicated than we ever anticipated.”

Cheeseman and members of his Whitehead laboratory have discovered many of the molecular movers and shakers that ensure chromosomes get to the right place at the right time. These components assemble together — like the parts of an engine — to establish robust connections with chromosomes and ultimately power their movement within cells. “The most important unanswered question in the field is how do these components work together? That is, how do you build a machine that is more than the sum of its parts?” he says.

Now, in two recent papers in the journals eLife and Current Biology, Cheeseman and his colleagues help shed light on this central question.

Back to the drawing board

As recently as 15 years ago, scientists assumed that in dividing cells, chromosomes move the way many other cellular objects move — transported by tiny molecular motors. These mini-motors are specifically designed to travel along roads made from rod-like structures called microtubules. Like a car cruising on a highway, they can carry cargo over long distances. Although such microtubule-based vehicles seemed a logical suspect, when scientists inactivate them in human cells, chromosomes can still move and segregate just fine. So something else must contribute the necessary molecular muscle.

“We basically had to throw out the major hypothesis that was out there and go back to the drawing board,” says Cheeseman.

Over the last several years, he and other scientists in the field have helped develop a clearer view of how this process works and who the key players are that enable a very different type of movement. Consider a car sitting motionless on a highway. Rather than revving its own engine to generate motion, the highway itself moves, shrinking or growing while the car hangs on. “It is a radically different way of imagining this movement process,” says Cheeseman. “An important part of my lab’s mission has been to figure out how do you build a motor like that? What are the factors required and how do they act?”

Of course, the highway — or more precisely, the microtubule — must grow and shrink as needed. But even more important, there must also be an apparatus that can enable chromosomes to hold on to such a dynamic structure. As Cheeseman and his colleagues have uncovered, this coupling requires a suite of highly sophisticated molecular players.

Building an unusual machine

Cheeseman and his laboratory have focused on three key groups or complexes of proteins that play essential roles in chromosome segregation in human cells. These components assemble together to form a kind of molecular tether point on chromosomes (called the kinetochore) where microtubules attach.

Diagram of the kinetochore/microtube interface
Diagram of the kinetochore/microtube interface
Courtesy: David Kern/Whitehead Institute

Among this trio of parts, the most critical is the Ndc80 complex. “It is the major connection between the kinetochore and the microtubule,” says Cheeseman. As a postdoc, he discovered the biochemical properties that enable this Ndc80 complex to grab on to microtubules, research that sparked his lab’s quest to study the various pieces of the kinetochore machinery and how they work.

While Ndc80 forms a critical linkage, it lacks some key capabilities, like processivity — the ability to keep ahold of something while it moves. In a series of papers, one published in 2009, another in 2012, and a new one in Current Biology, Cheeseman’s team revealed that Ska1 can perform this crucial function. That is, it has the biochemical capacity to enable chromosomes to hang onto microtubules while they grow and as they shrink, an activity that it can impart to the Ndc80 complex. “These are pretty powerful properties,” says Cheeseman.

Diving even deeper into Ska1’s bag of tricks, Julie Monda and Ian Whitney, lead authors of the Current Biology paper, went on to decipher the precise molecular features that enable the complex’s dynamic capabilities, uncovering multiple surfaces that associate with microtubules and enable Ska1 to undergo something akin to molecular somersaults. These somersaults are what allow it to maintain its association with microtubules.

The third complex, Astrin-SKAP, also plays a unique role. As Cheeseman’s team described in their recent eLife paper, led by first author David Kern, it serves as a master stabilizer — like a final drop of superglue to secure everything in place. “It’s the last thing that comes in and helps lock down these interactions, so you can stabilize and maintain them,” says Cheeseman.

Uncovering its role was no easy feat. Astrin-SKAP proved to be rather temperamental biochemically, complicating Kern’s efforts to purify and manipulate it in the laboratory. Also, as he and his colleagues discovered, a tiny piece of the structure had previously gone undetected; it works alongside the rest of the complex and is required for its normal function. Perhaps the most important revelation was that Astrin-SKAP doesn’t just work alone — it also coordinates with Ndc80. “This is an important finding for how we think about these components as a whole,” saysCheeseman.

Although questions remain about how all of these parts work together and how other pieces may come into play, Cheeseman believes these studies provide an exciting start. “The first human kinetochore component wasn’t identified until 1987, when many of the other key processes in the cell had already been intensively studied,” he says. “There are so many exciting questions that are accessible now that we have these tools and knowledge.”

Now, he and his colleagues will continue to meld approaches in cell biology and biochemistry to decode the inner workings of the kinetochore. That includes understanding how the various components operate not only in individual cells, but also in multicellular organisms.

“We are currently thinking a lot about the physiological context— that is, what matters to cells and to an organism,” says Cheeseman. “The work that our lab and others have conducted over the past two decades has given us a molecular handle on this problem. I’m excited to be able to apply these finding to understanding the ways that cell division is altered in development and in disease states.”

Written by Nicole Davis
* * *
Iain Cheeseman’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also an associate professor of biology at Massachusetts Institute of Technology.
* * *
Full citations:
“Astrin-SKAP complex reconstitution reveals its kinetochore interaction with microtubule-bound Ndc80”
eLife 2017;6:e26866 August 25, 2017. DOI: 10.7554/eLife.26866
David M Kern (1,2), Julie K Monda (1,2), Kuan-Chung Su (1), Elizabeth M Wilson-Kubalek (3), and Iain M Cheeseman (1,2).
1. Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
3. Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
“Microtubule tip tracking by the spindle and kinetochore protein Ska1 requires diverse tubulin-interacting surfaces”
Current Biology, online November 16, 2017. DOI: 10.1016/j.cub.2017.10.018
Julie K. Monda (1,2,6), Ian P. Whitney (1,6), Ekaterina V. Tarasovetc (3,4), Elizabeth Wilson-Kubalek (5), Ronald A. Milligan (5), Ekaterina L. Grishchuk (3), and Iain M. Cheeseman (1,2).
1. Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA
3. Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia
5. Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
6. These authors contributed equally
Alan D. Grossman

Education

  • PhD, 1984, University of Wisconsin, Madison
  • BS, 1979, Biochemistry, Brown University

Research Summary

We use a variety of approaches to investigate several of the fundamental and conserved processes used by bacteria for propagation and growth, adaptation to stresses, and acquisition of new genes and traits via horizontal gene transfer. Our long term goals are to understand many of the molecular mechanisms and regulation underlying basic cellular processes in bacteria. Our organism of choice for these studies is usually the Gram positive bacterium Bacillus subtilis.

Our current efforts are focused in two important areas of biology: 1) The control of horizontal gene transfer, specifically the lifecycle, function, and control of integrative and conjugative elements (ICEs). These elements are widespread in bacteria and contribute greatly to the spread of antibiotic resistances between organisms. 2) Regulation of the initiation of DNA replication and the connections between replication and gene expression, with particular focus on the conserved replication initiator and transcription factor DnaA. This work is directly related to mechanisms controlling bacterial growth, survival, and stress responses.

Awards

  • National Academy of Sciences, 2014
  • American Academy of Arts and Sciences, 2008
  • American Academy of Microbiology 1998
  • Eli Lilly Company Research Award, 1997
New player in cellular signaling

Researchers have identified a key nutrient sensor in the mTOR pathway that links nutrient availability to cell growth.

Nicole Giese Rura | Whitehead Institute
November 9, 2017

To survive and grow, a cell must properly assess the resources available and couple that with its growth and metabolism — a misstep in that calculus can potentially cause cell death or dysfunction. At the crux of these decisions is the mTOR pathway, a cellular pathway connecting nutrition, metabolism, and disease.

The mTOR pathway incorporates input from multiple factors, such as oxygen levels, nutrient availability, growth factors, and insulin levels to promote or restrict cellular growth and metabolism. But when the pathway runs amok, it can be associated with numerous diseases, including cancer, diabetes, and Alzheimer’s disease. Understanding the various sensors that feed into the mTOR pathway could lead to novel therapies for these diseases and even aging, as dialing down the mTOR pathway is linked to longer lifespans in mice and other organisms.

Although the essential amino acid methionine is one of the key nutrients whose levels cells must carefully sense, researchers did not know how it fed into the mTOR pathway — or if it did at all. Now, Whitehead Institute Member David Sabatini and members of his laboratory have identified a protein, SAMTOR, as a sensor in the mTOR pathway for the methionine derivative SAM (S-adenosyl methionine). Their findings are described in the current issue of the journal Science.

Methionine is essential for protein synthesis, and a metabolite produced from it, SAM, is involved in several critical cellular functions to sustain growth, including DNA methylation, ribosome biogenesis, and phospholipid metabolism. Interestingly, methionine restriction at the organismal level has been linked to increased insulin tolerance and lifespan, similar to the antiaging effects associated with inhibition of mTOR pathway activity. But the connection between mTOR, methionine, and aging remains elusive.

“There are a lot of similarities between the phenotypes of methionine restriction and mTOR inhibition,” says Sabatini, who is also a Howard Hughes Medical Institute investigator and a professor of biology at MIT. “The existence of this protein SAMTOR provides some tantalizing data suggesting that those phenotypes may be mechanistically connected.”

Sabatini identified mTOR as a graduate student and has since elucidated numerous aspects of its namesake pathway. He and his lab recently pinpointed the molecular sensors in the mTOR pathway for two key amino acids: leucine and arginine. In the current line of research, co-first authors of the Science paper Xin Gu and Jose Orozco, both graduate students Sabatini’s lab, identified a previously uncharacterized protein that seemed to interact with components of the mTOR pathway. After further investigation, they determined that the protein binds to SAM and indirectly gauges the pool of available methionine, making this protein — SAMTOR — a specific and unique nutrient sensor that informs the mTOR pathway.

“People have been trying to figure out how methionine was sensed in cells for a really long time,” Orozco says. “I think that this is the first time in mammalian cells a mechanism has been found to describe the way methionine can regulate a major signaling pathway like mTOR.”

The current research indicates that SAMTOR plays a crucial role in methionine sensing. Methionine metabolism is vital for many cellular functions, and the Sabatini lab will further investigate the potential links between SAMTOR and the extended lifespan and increased insulin sensitivity effects that are associated with low methionine levels.

“It is very interesting to consider mechanistically how methionine restriction might be associated in multiple organisms with beneficial effects, and identification of this protein provides us a potential molecular handle to further investigate this question,” Gu says. “The nutrient-sensing pathway upstream of mTOR is a very elegant system in terms of responding to the availability of certain nutrients with specific mechanisms to regulate cell growth. The currently known sensors raise some interesting questions about why cells evolved sensing mechanisms to these specific nutrients and how cells treat these nutrients differently.”

This work was supported by the National Institutes of Health, the Department of Defense, the National Science Foundation, and the Paul Gray UROP Fund.

School of Science welcomes new faculty members

This fall brings 14 new professors in the departments of Biology, Chemistry, Mathematics, and Physics.

School of Science
October 10, 2017

This fall, the MIT School of Science has welcomed 14 new professors in the departments of Biology, Chemistry, Mathematics, and Physics.

Ian J. M. Crossfield focuses on the atmospheric characterization of exoplanets through all possible methods — transits, eclipses, phase curves, and direct imaging — from the ground and from space, with an additional interest in the discovery of new exoplanets, especially those whose atmospheres that can be studied in more detail. He joins the MIT Department of Physics as an assistant professor.

Joey Davis, an assistant professor in the Department of Biology, studies the molecular mechanisms underpinning autophagy using biochemical, biophysical, and structural biology techniques such as mass spectrometry and cryo-electron microscopy. This pathway is responsible for protein and organelle degradation and has been linked to a variety of aging associated disorders including neurodegeneration and cancer.

Daniel Harlow works on black holes and cosmology, viewed through the lens of quantum gravity and quantum field theory. He has joined the Department of Physics as assistant professor.

Philip Harris, a new assistant professor in the Department of Physics, searches for dark matter, seeking a deeper understanding of the petabytes of data collected at the Large Hadron Collider. Much of his research exploits new techniques to resolve the structure of quark and gluon decays, known as jet substructure.

Or Hen studies quantum chromodynamics effects in the nuclear medium, and the interplay between partonic and nucleonic degrees of freedom in nuclei, conducting experiments at the Thomas Jefferson and Fermi National Accelerator Laboratories, as well as other accelerators around the world. He has joined the faculty as an assistant professor in the Department of Physics and the Laboratory of Nuclear Science.

Laura Kiessling investigates how carbohydrates are assembled, recognized, and function in living cells, which is crucial to understanding key biological processes such as bacterial cell wall biogenesis, bacteria chemotaxis, enzyme catalysis and inhibition, immunity, and stem cell propagation and differentiation. She is the new Novartis Professor of Chemistry.

Rebecca Lamason investigates how intracellular bacterial pathogens hijack host cell processes to promote infection. In particular, she studies how Rickettsia parkeri and Listeria monocytogenes move through tissues via a process called cell-to-cell spread. She has joined the Department of Biology as an assistant professor.

Sebastian Lourido studies the molecular events that enable parasites in the phylum Apicomplexa to remain widespread and deadly infectious agents. Lourido uses Toxoplasma gondii to model processes conserved throughout the phylum, in order to expand our understanding of eukaryotic diversity and identify specific features that can be targeted to treat parasite infections. He has been welcomed into the Department of Biology as an assistant professor.

Ronald T. Raines, who has joined the faculty as the Firmenich Professor of Chemistry, uses techniques that range from synthetic chemistry to cell biology to illuminate in atomic detail both the chemical basis and the biological purpose for protein structure and protein function. He seeks insights into the relationship between amino-acid sequence and protein function (or dysfunction), as well as to the creation of novel proteins with desirable properties.

Giulia Saccà is an algebraic geometer with a focus on hyperkähler and Calabi-Yau manifolds, K3 surfaces, moduli spaces of sheaves, families of abelian varieties and their degenerations, and symplectic resolutions. She is now an assistant professor in the Department of Mathematics.

Stefani Spranger studies the interactions between cancer and the immune system, with the goal of improving existing immunotherapies or developing novel therapeutic approaches. Spranger seeks to understand how CD8 T cells, otherwise known as killer T cells, are excluded from the tumor microenvironment, with a focus on lung and pancreatic cancers. She has joined the Department of Biology as an assistant professor.

Daniel Suess works at the intersection of inorganic and biological chemistry, studying redox reactions that underpin global biogeochemical cycles, metabolism, and energy conversion. He develops chemical strategies for attaining precise, molecular-level control over the structures of complex active sites. In doing so, his research yields detailed mechanistic insight and enables the preparation of catalysts with improved function. Suess is an assistant professor in the Department of Chemistry.

Wei Zhang is a number theorist who works in arithmetic geometry, with special interest in fundamental objects such as L-functions, which appear in the Riemann hypothesis and its generalizations, and are central to the Langlands program. Zhang has joined the Department of Mathematics as a full professor.

Yufei Zhao, who has joined the Department of Mathematics as an assistant professor, works in combinatorics and graph theory, and is especially interested in problems with extremal, probabilistic, and additive flavors.