Research Area: Stem Cell and Developmental Biology

Mary Gehring

Education

  • PhD, 2005, University of California, Berkeley
  • BA, 1998, Biology, Williams College

Research Summary

We focus on plant epigenetics — that is, the heritable information that influences cellular function but is not encoded in the DNA sequence itself. We use genetic, genomic and molecular biology approaches to study the fidelity of epigenetic inheritance and the dynamics of epigenomic reprogramming during reproduction, primarily in the model plant Arabidopsis thaliana. More specifically, we investigate the interplay among repetitive sequences, DNA methylation and chromatin structure in these dynamic processes.

Awards

  • Rosalind Franklin Young Investigator Award, 2013
  • Pew Scholar in the Biomedical Sciences, 2011
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
Retinoic acid regulates transitions in mouse sperm production
November 7, 2017

CAMBRIDGE, MA – Sperm production requires progression through a well-orchestrated series of transitions in the testes that move diploid spermatogonia cells, with two complete sets of chromosomes, through a series of transitions to produce haploid sperm, with one copy of each chromosome, poised to swim and fertilize an available egg. There are four major transitions in sperm production, or spermatogenesis. The first is spermatogonial differentiation, during which spermatogonia differentiate, losing their stem-cell like qualities. The resulting spermatocytes then initiate meiosis and undergo two rounds of cell division to generate haploid spermatids. The spermatids undergo elongation and then the resulting sperm are released.

The signals that control progression through these transitions were poorly understood until 2015, when David Page, Member and Director of Whitehead Institute, professor of biology at Massachusetts Institute of Technology, and investigator with Howard Hughes Medical Institute and colleagues determined that retinoic acid (RA), a derivative of vitamin A that has been shown to play a key role in a number of developmental processes, was responsible for coordinating the first two stages of spermatogenesis-differentiation and meiosis. Now, in a paper published this week in the journal Proceedings of the National Academy of Sciences, Page, first author Tsutomu Endo, and colleagues extend those findings to show that RA signaling in mice coordinates the second two transitions as well.

Diagram of model by which retinoic acid coordinates spermatogenesisThe researchers used chemical manipulation of RA levels to determine that RA controlled the second two transitions, spermatid elongation and sperm release, in addition to the first two. With this knowledge in hand, the researchers were then able to drill down and get a better picture of how RA regulates male gamete production. One outstanding question has been how males are able to continually produce sperm throughout their lifetime, in contrast with females whose egg production and maturation is limited. Page and colleagues measured RA levels in the testes and discovered that it is cyclically produced, driving production of sperm during the male lifetime. In addition to the timing of RA production, the researchers also examined its source. From which cells was the RA signal coming? During the first two transitions, they determined that the RA was coming from the somatic Sertoli cells, the support cells of the testes, and in the second two transitions they determined that it was being released by the germ cells themselves-the meiotic (pachytene-stage) spermatocytes were found to be secreting RA to other germ cells in the testes.

These findings not only contribute to our fundamental understanding of male gamete formation, they also provide important clues for the field of reproductive technology. For years, scientists have been working on making gametes in the laboratory, but have had difficulty making functional sperm. This discovery of the role of RA in spermatogenesis adds important tools to the toolbox of assisted reproduction. The work shows that RA is required in both the early and late transitions of spermatogenesis and sheds light on an important component of laboratory efforts for sperm production.

Other researchers involved include Elizaveta Freinkman and Dirk G. de Rooij.

This research was supported by Howard Hughes Medical Institute (HHMI) and the United States Department of Defense (DoD W81XWH-15-1-0337)

Written by Lisa Girard
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David Page’s primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute Investigator and a Professor of Biology at the Massachusetts Institute of Technology.
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Paper cited: Endo, T et al.  Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis. Proc Natl Acad Sci. DOI: 10.1073/pnas.1710837114. Epub 2017 Nov 6.
Other work cited: Endo T et al. Periodic retinoic acid-STRA8 signaling intersects with periodic germ-cell competencies to regulate spermatogenesis. Proc Natl Acad Sci. DOI: 10.1073/pnas.1505683112. Epub 2015 Apr 20.
Genetic body/brain connection identified in genomic region linked to autism
October 6, 2017

CAMBRIDGE, Mass. – For the first time, Whitehead Institute scientists have documented a direct link between deletions in two genes—fam57ba and doc2a—in zebrafish and certain brain and body traits, such as seizures, hyperactivity, enlarged head size, and obesity.

“Finding the molecular connections between a brain and a body phenotype is indeed really paradigm shifting,” says Whitehead Institute Member Hazel Sive, who is also a professor of biology at MIT. “It lets us think about the common control of these two aspects of phenotype, which is very interesting and could be useful for developing therapies for these phenotypes.”

Both genes reside in the 16p11.2 region of human chromosome 16. About 1 in 2000, or around 4 million people worldwide, have deletions in this region, and these deletions are associated with multiple brain and body symptoms, including autism spectrum disorders, developmental delay, intellectual disability, seizures, and obesity.

Scientists have had difficulty teasing apart the relationship between specific traits and deletions in this region, because it includes at least 25 genes, and because there is not a one-to-one mapping of gene to phenotype. Instead, multiple genes seem to create a web of interactions that produce a variety of characteristics.

To solve such a complex puzzle, Jasmine McCammon, a postdoctoral researcher in Sive’s lab, enlisted the zebrafish as a “living test tube”.  The Sive group uses zebrafish to study the genetic/phenotype connections associated with human disorders. Like the human genome, the zebrafish genome has two copies of each gene, and scientists can remove the function of multiple genes to produce phenotypes that are reminiscent of human symptoms.

The results from McCammon’s initial screen with zebrafish indicate that two genes in the 16p11.2 region could be key for brain development: fam57ba and doc2a. (fam57b encodes a ‘ceramide synthase’ that makes a kind of lipid, and doc2a encodes a regulator of secretion.) McCammon investigated further by deleting one copy of fam57ba and doc2a individually; the effect was minimal. However, simultaneously removing a copy of both genes revealed significant synergy between them. Compared with controls, fish with only one copy of each gene exhibit hyperactivity, increased propensity for seizures, increased body and head size, and fat content. When both copies of only fam57ba are removed, the fish are much larger and with a higher fat content. All of the study’s results are published in the journal Human Molecular Genetics.

Although her findings use zebrafish and are far from the clinic, McCammon was struck by how much people affected by deletions in this genome identified with her results.

“When I spoke with the parents of some kids with neurodevelopmental disorders, I was surprised how much the brain/body connection that we described resonated with them,” she says. “They said that yes, their child has autism, but he also has really weak muscle tone. Or she has a gastrointestinal problem and that’s been more problematic than her behavior issues. For me, it’s been really revealing to talk to people who’ve actually experienced this as opposed to reading about statistics in journals.”

The mechanisms underlying this brain/body connection are still not well understood. One of the identified genes, fam57ba, provides some intriguing hints as to how metabolism and brain function could be intertwined, because it produces an enzyme that plays a role in lipid production and is believed to be a metabolic regulator.  The lipid type, ceramide, also has a functional role in various signaling pathways and affects synaptic function, although its primary role is not in the synapse, but providing structure in cell membranes.

For Sive, the two identified genes could be just the beginning. “Our data suggest that there may be metabolic genes involved in human neurodevelopmental disorders,” she says.  “This is a nascent field, that we’re very interested in going forward.”

This work was supported by Jim and Pat Poitras, Len and Ellen Polaner, and the Markell-Balkin-Weinberg Postdoctoral Fellowship.

Written by Nicole Giese Rura
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Hazel Sive’s primary affiliation is with Whitehead Institute for Biomedical Research, where her laboratory is located and all her research is conducted. She is also a professor of biology at Massachusetts Institute of Technology.
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Full Citation:
“The 16p11.2 homologs fam57ba and doc2a generate certain brain and body phenotypes”
Human Molecular Genetics, Volume 26, Issue 19, 1 October 2017.
Jasmine M. McCammon(1), Alicia Blaker-Lee(1), Xiao Chen(2), and Hazel Sive (1,2).
1. Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Department of Biology hosts its first Science Slam

Eight biology trainees had just three minutes to explain their research and earn favor with the judges and audience in new yearly event.

Raleigh McElvery | Department of Biology
October 5, 2017

Nearly 300 spectators crowded into a lecture hall at the Ray and Maria Stata Center on a recent Tuesday to witness the first annual Science Slam, hosted by MIT’s Department of Biology.

A science slam features a series of short presentations where researchers explain their work in a compelling manner and — as the name suggests — make an impact. The presentations aren’t just talks, they’re performances geared towards a science-literate but non-specialized public audience. In this case, competitors were each given one slide and three minutes to tell their scientific tales and earn votes from audience members and judges.

The jury included Ellen Clegg, editorial page editor of The Boston Globe and co-author of two award-winning books, “ChemoBrain” and “The Alzheimer’s Solution;” Emilie Marcus, CEO of Cell Press and editor-in-chief of the flagship journal, Cell; and Ari Daniel, an independent science reporter who produces digital videos for PBS NOVA and co-produces the Boston branch of Story Collider.

Among the competitors were five graduate students and three postdocs who hailed from labs scattered throughout Building 68, the Whitehead Institute, the Broad Institute, the Koch Institute for Integrative Cancer Research, and the Picower Institute for Learning and Memory. The storytellers were:

  • Sahin Naqvi, from David Page’s lab, who spoke about the evolution of genetic sex differences in mammals, as well as how these differences impact the likelihood of developing certain diseases based on gender;
  • Sudha Kumari, from Darrell Irvine’s lab, who spoke about her work investigating immune cell interactions — specifically how T cells communicate using physical contact;
  • Deniz Atabay, from Peter Reddien’s lab, who spoke about the ways cells in flatworms self-organize during regeneration to re-form organs, tissues, and even neural circuits;
  • Emma Kowal, from Christopher Burge’s lab, who spoke about her goals to demystify the ways in which certain noncoding regions of genetic sequence, known as introns, contribute to protein production;
  • Xin Tang, from Rudolf Jaenisch’s lab, who spoke about a technique to illuminate the seemingly invisible changes in brain cells that trigger disease, using a glowing enzyme from a firefly;
  • Nicole Aponte, from Troy Littleton’s lab, who spoke about her ability to manipulate brain cell activity in the fruit fly, and study how defects in neuronal connections contribute to developmental disorders;
  • Karthik Shekhar, from Aviv Regev’s lab, who spoke about his efforts to identify and manipulate different types of brain cells, understanding how they assemble into complex networks to facilitate learning, memory, and — in some cases — disease; and
  • Monika Avello, from Alan Grossman’s lab, who spoke about “bacterial sexology,” that is, how and why these organisms choose to block unwanted sexual advances from fellow bacteria.

Vivian Siegel, who oversees the department’s communications efforts, moderated the event. Siegel and the Building 68 communications team joined forces with three members of the Building 68 MIT Postdoctoral Association — Ana Fiszbein, Isabel Nocedal, and Peter Sudmant — to publicize the event and to host two pre-slam workshops, as well as one-on-one training sessions with individual participants.

“Participating in a Science Slam seemed like a great way for our trainees to learn how to communicate to a nonspecialized audience, which is something they will need to be able to do throughout their careers,” Siegel said. “We really wanted to develop a camaraderie among the participants, and bring trainees together from across the department to help each other tell compelling stories about their science.”

Kowal — whose talk was titled “Gone but Not Forgotten: How Do Introns Enhance Gene Expression?”  — ultimately took home both the audience and jury cash prizes. Kowal completed her undergraduate degree in chemical and physical biology at Harvard before coming to MIT for graduate school. Her dream is to write science fiction, so she decided she’d better study science so she’d know what to write about.

“I really enjoyed seeing people get stoked about introns, and the fact that they enhance gene expression,” she said. “It’s a great way to get comfortable explaining your project in a compelling way to a broad audience. Since you’ll probably be telling people about your work for a while, I think it’s a very good use of time to practice doing that.”

Three MIT biologists receive NIH Outstanding Investigator Awards

Graham Walker, Michael Yaffe, and Robert Weinberg earn support from the National Institutes of Health to further their research endeavors.

Raleigh McElvery | Department of Biology
September 19, 2017

This fall, two faculty members from the MIT Department of Biology received R35 Outstanding Investigator Awards sponsored by the National Institute of Environmental Health Sciences (NIEHS), while a third garnered the same distinction from the National Cancer Institute (NCI). These awards provide long-term support to experienced investigators with outstanding records of research productivity as they undertake lengthy projects with unusual potential.

Graham Walker, the American Cancer Society Professor in the Department of Biology at MIT, a member of the Center for Environmental Health Sciences, and affiliate member of the Koch Institute for Integrative Cancer Research, is one of two biology faculty to earn the R35 Outstanding Investigator Award from the NIEHS.

This award is supported by the NIEHS through the Revolutionizing Innovative, Visionary Environmental health Research (RIVER) program. The program recognizes outstanding investigators in the field of environmental health, potentially offering up to $750,000 per year over the next eight years.

The awardees include both mid-career and senior researchers, whose work spans many aspects environmental health science — including technology development, mechanistic, clinical, and epidemiological research. A total of eight investigators received the NIEHS RIVER R35 this year.

“The RIVER program is designed to fund people, not projects,” said David Balshaw, chief of the NIEHS Exposure, Response, and Technology Branch who leads the NIEHS team overseeing this initiative. “It gives outstanding environmental health scientists stable funding, time, and, importantly, flexibility to pursue creative scientific ideas, rather than constantly writing grants to support their research programs.”

Walker will use his award to continue investigating the fundamental mechanisms of mutagenesis and DNA repair, with a special emphasis on the Rev1/3/7-dependent pathway of mutagenic translation synthesis found in eukaryotes, including humans. He and his colleagues recently published evidence suggesting that inhibiting this pathway could potentially improve chemotherapy.

Michael Yaffe, the David H. Koch Professor of Science at MIT, a member of the Koch Institute and the Center for Environmental Health Sciences, and attending surgeon at the Beth Israel Deaconess Medical Center, also received a NIEHS RIVER R35 award.

Yaffe’s work concerns how cells respond to injury, including damage to DNA and RNA molecules arising because of the environment and in response to drugs used to treat cancer. He is also interested in the relationship between inflammation, blood clotting, and cancer. He employs multidisciplinary approaches harnessing techniques from biochemistry, structural and cell biology, computer science, and systems biology/engineering.

Yaffe will use his funds to further a project investigating the roles of protein kinases in coordinating cellular responses to damage to both DNA and RNA molecules.

Robert Weinberg, founding member of the Whitehead Institute, professor of biology at MIT, an affiliate member of the Koch Institute, and director of the MIT Ludwig Center for Molecular Oncology, has received his R35 Outstanding Investigator Award from the NCI.

The award provides up to $600,000 per year over seven years to accomplished cancer researchers, nominated by their institutions, who have served as principal investigators on an NCI grant for the last five years. A total of 18 investigators received the NCI Outstanding Investigator Award this year.

“The NCI Outstanding Investigator Award addresses a problem that many cancer researchers experience: finding a balance between focusing on their science while ensuring that they will have funds to continue their research in the future,” said Dinah Singer, director of NCI’s Division of Cancer Biology. “With seven years of uninterrupted funding, NCI is providing investigators the opportunity to fully develop exceptional and ambitious cancer research programs.”

Weinberg is a pioneer in cancer research, best known for his role in discovering the first human oncogene — a gene that, when activated, can spur tumor growth. His lab is also credited with isolating the first known tumor suppressor gene.

He will use his funds to delve into the mechanisms of metastasis — the process that allows cancer cells to spread. He aims to learn more about how these cells disseminate from primary tumors, as well as how they become established in distant tissues after they metastasize.

Department of Biology welcomes three new faculty members

Recent additions bring diverse expertise and cultural perspectives to research community.

Raleigh McElvery | Department of Biology
July 25, 2017

On July 1, MIT Department of Biology welcomed three new faculty members. Since they were all born outside the continental U.S., these newcomers add to the diversity of cultural experiences and contribute to the global face of science at MIT and its affiliated institutions around Kendall Square. The triad also enhances the department’s diverse array of research initiatives. Their interests are as far-reaching as their roots, and range from investigating genetic diseases and cancer immunotherapy to exploiting parasite vulnerabilities.

“When creative individuals with distinct perspectives and approaches come together in an innovative environment like MIT, the possibilities for scientific collaboration and accomplishment are exceptional,” says Alan Grossman, head of the department. “I couldn’t be more pleased to welcome three such outstanding and accomplished individuals into our research community.”

Eliezer Calo

Eliezer Calo is no stranger to MIT. Although he grew up on a farm more than a thousand miles away in the mountains of Carolina, Puerto Rico, Calo first set foot in MIT’s Building 68 11 years ago — and hasn’t wavered in his decision to become a biologist since. In 2006, as part of the MIT Summer Research Program (MSRP), Calo spent 10 weeks studying under Professor Stephen Bell, examining DNA replication. At the time, Calo was a chemistry major at the University of Puerto Rico, but returned post-graduation to MIT’s Department of Biology, earning his PhD while serving as both a teaching assistant for MIT’s course 7.01 (Introduction to Biology) and MSRP program assistant.

“MIT is very unique,” he says. “I’ve done research at multiple institutions, and yet nothing quite compares. Here, the impossible is made possible.”

After completing his postdoctoral training at Stanford University, Calo returned to Cambridge, Massachusetts, this past January as an assistant professor and extramural member at the Koch Institute to head his own lab — exploring the ways in which errors in cellular organelles called ribosomes can lead to disease.

Ribosomes are vital to the translation of genetic code into the molecules integral to life, but are far less often acknowledged for their role in embryonic development. Calo suggests that when ribosomes are not constructed correctly, they are unable to carry out their cellular duties, hindering cell growth and causing developmental disorders. Calo is interested in one condition specifically: Treacher Collins syndrome, which stems from a mutation in a single gene that impedes proper ribosomal assembly. He will soon transfer his experiments from cell cultures to a new model system — zebrafish — in order to further unravel the relationship between ribosome structure and disease.

“The research I do now is purely based on my interest in understanding how cells work,” Calo says. “Specifically, how the mechanisms controlling growth and proliferation operate. These are essential processes that led to the emergence of multicellular organisms, and thus to our own existence.”

Stefani Spranger

One building over in MIT’s Koch Institute, newly-appointed Assistant Professor Stefani Spranger will work to harness the body’s own defense force to pinpoint and eradicate cancer. Spranger carried her passion for immunotherapy across seas from Munich, Germany. As the daughter of two engineers, Spranger was raised on science. “My parents fostered my curiosity,” she says, “which led to my initial motivation to go into science: to figure out how things work.”

While earning her bachelor’s and master’s degrees from the Ludwig-Maximilians University of Munich, Spranger discussed publications focusing on two clinical trials that used engineered immune cells to combat malignant melanoma. These publications ignited Spranger’s enthusiasm for immune-based therapies, which in turn spurred her doctoral and postdoctoral training at the Helmholtz-Zentrum Munich in the Institute for Molecular Immunology and the University of Chicago, respectively.

While Spranger’s education helped hone her immunology research skills, she is excited to experience a more varied academic environment encompassing a range of disciplines. “I was drawn to MIT because of its diverse faculty and the breadth of research interests,” she says.

Spranger’s lab will employ tumor models in mice to determine how cancer and immune cells interact. In particular, she aims to discern the many factors related to the cells, tissues, and environment that could affect the immune system’s anti-tumor response. Ultimately, Spranger hopes to contribute to new treatments that trigger the body’s defense to thwart cancer.

Sebastian Lourido

Trained as both an artist and a scientist, Sebastian Lourido works to counter an entirely different kind of invader spreading biological mayhem: parasites. Originally from Colombia, he was recently named assistant professor of biology, joining the cohort of 15 faculty members at the Whitehead Institute for Biomedical Research — one of just 28 individuals to ever receive this appointment. The title may be new, but this is familiar turf for Lourido. He became a Whitehead Fellow in 2012, after receiving his PhD in microbiology from Washington University in St. Louis and a bachelor’s in studio art and cell and molecular biology from Tulane University. A pioneer in more ways than one, Lourido formed his own lab as a fellow rather than following a more conventional postdoc path.

Lourido spent much of his childhood exploring his mother’s genetics lab, where he analyzed practically anything he could fit under a microscope. “That experience solidified my excitement for the invisible mechanisms that make up the living world,” he says. “I can’t remember a time when I didn’t know that genetic information was carried in our cells in the form of DNA, and passed from one generation to the next.”

Constantly seeking ways to merge his artistic endeavors with scientific ones, Lourido leverages his creativity to glean insight into the systems and structures that constitute life.  He probes a group of microscopic invaders known as Apicomplexan parasites, revealing their weaknesses in order to devise potential treatments. Lourido’s team was the first to perform a genome-wide functional analysis of an apicomplexan — gaining deeper understanding of the genes and molecules key for the invasion process. In 2013, Lourido received the National Institutes of Health (NIH) Director’s Early Independence Award, and with it a five-year grant to investigate motility in one kind of parasite, Toxoplasma gondii. This same interloper is also the subject of Lourido’s two-year NIH-funded project, for which he is the principal investigator.

Lourido has found the MIT community both welcoming and inclusive. Even as he was interviewing for his new position, he was struck by the collaborative, collegial, and nurturing environment.

“This level of engagement permeates the other elements of our community — students, postdocs, and staff scientists — who drive the exciting research happening every day at MIT,” he says. “There are many forces that shape the diversity of our campus, and we need to be vigilant and work hard to continue to encourage and support scientists from different backgrounds, experiences, and cultures.”

School of Science professors granted tenure

Seven award-winning faculty members represent the departments of Physics, Chemistry, and Biology.

Bendta Schroeder | School of Science
June 28, 2017

The School of Science has announced that seven of its faculty members have been granted tenure by MIT.

This year’s newly-tenured professors are:

Mircea Dincă, associate professor in the Department of Chemistry, addresses research challenges related to the storage and consumption of energy and global environmental concerns through the synthesis and characterization of new inorganic and organic materials. His work has applications in heterogeneous catalysis, energy conversion and storage, chemical sensing, gas separation, and water-based technologies including adsorption heat pumps and water production and purification. By designing and synthesizing new materials, Dincă aims to learn more about fundamental processes such as electron and ion transport through ordered solids, the reactivity and electrochemistry of low-coordinate metal ions in porous crystals, the effects of conformational changes on the electronic properties of molecules, and the behavior of materials at the interface with solid-state devices.

Dincă earned a BS in chemistry at Princeton University and a PhD in inorganic chemistry at the University of California at Berkeley. Following a postdoc appointment at MIT in the Department of Chemistry, he joined its faculty in 2010. Among Dincă’s awards and honors are an Alfred P. Sloan Research Fellowship, a Camille Dreyfus Teacher-Scholar Award, and the Alan T. Waterman Award

Liang Fu, the Lawrence C. (1944) and Sarah W. Biedenharn Career Development Assistant Professor in the Department of Physics, is interested in novel topological phases of matter and their experimental realizations. He works on the theory of topological insulators and topological superconductors, with a focus on predicting and proposing their material realizations and experimental signatures. He is also interested in potential applications of topological materials, ranging from tunable electronics and spintronics, to quantum computation.

Fu obtained a BS in physics from the University of Science and Technology of China and a PhD in physics from the University of Pennsylvania. Following an appointment as a Junior Fellow at Harvard University, he joined the MIT faculty in 2012. Fu is the recipient of a Packard Fellowship for Science and Engineering and the New Horizons in Physics Prize.

Jeff Gore, associate professor in the Department of Physics, uses experimentally-tractable microcosms such as bacterial communities to explore the physics of complex living systems, examining how interactions between individuals drives the evolution and ecology of communities. Gore’s primary areas of research include the behavior of populations near tipping points that lead to collapse, the evolution of cooperative behaviors within a species or community, and the determining factors for multi-species diversity within a community.

Gore received a BS in physics, mathematics, economics, and electrical engineering from MIT and a PhD in physics from the University of California at Berkeley. He returned to MIT as a Pappalardo Postdoctoral Fellow in the Department of Physics and subsequently joined the faculty in 2010. Gore’s awards and honors include an Allen Distinguished Investigator Award, an NIH Director’s New Innovator Award, and a National Science Foundtion CAREER Award.

Jeremiah Johnson, the Firmenich Career Development Associate Professor in the Department of Chemistry, designs macromolecules and their syntheses to address problems in chemistry, medicine, biology, energy, and polymer physics. Johnson works with a range of materials and applications, including nano-scale, brush-arm star polymer architectures for in vivo drug delivery, imaging, and self-assembly; hydrogels for the analysis of how molecular network defects impact mechanics; and polymers for surface functionalization and energy storage.

Johnson completed a BS in biomedical engineering and chemistry at Washington University in St. Louis and a PhD in chemistry at Columbia University. Following an appointment as a Beckman Institute Postdoctoral Scholar at the Caltech, Johnson joined the MIT faculty in 2011. Johnson is the recipient of several awards including an Alfred P. Sloan Research Fellowship and a 3M Non-Tenured Faculty Award.

Brad Pentelute, the Pfizer-Laubach Career Development Associate Professor in the Department of Chemistry, modifies naturally occurring proteins to enhance their therapeutic properties for human medicine, focusing on the use of cysteine arylation to generate abiotic macromolecular proteins, the precision delivery of biomolecules into cells, and the development of fast flow platforms to rapidly produce polypeptides.

Pentelute earned a BS in chemistry and a BA in psychology at the University of Southern California, followed by a PhD in organic chemistry at the University of Chicago. After a postdoc fellowship at Harvard Medical School, Pentelute joined the MIT faculty in 2011. His awards and honors include an Alfred P. Sloan Research Fellowship, a Novartis Early Career Award, and an Amgen Young Investigator Award.

Jesse Thaler, associate professor of physics and member of the Laboratory for Nuclear Science, is a theoretical particle physicist whose research focus is the Large Hadron Collider (LHC) experiment at CERN. Thaler aims to maximize the discovery potential of the LHC by applying theoretical insights from quantum field theory. He is particularly interested in novel methods to test the properties of dark matter at the LHC and beyond, as well as the theoretical structures and experimental signatures of supersymmetry. Thaler also develops new methods to characterize jets, which are collimated sprays of particles that are copiously produced at the LHC. These techniques exploit the substructure of jets to enhance the search for new physics as well as to illuminate the structure of the standard model itself.

Thaler received his PhD in physics from Harvard University and his BS in mathematics and physics from Brown University. After a fellowship at the Miller Institute for Basic Research in Science at the University of California at Berkeley, he joined the MIT faculty in the Department of Physics in 2010. His awards and honors include an Early Career Research Award from the U.S. Department of Energy, a Presidential Early Career Award for Scientists and Engineers from the White House, an Alfred P. Sloan Research Fellowship, and an MIT Harold E. Edgerton Faculty Achievement Award.

Matthew Vander Heiden is the Eisen and Chang Career Development Associate Professor in the Department of Biology. His laboratory is studying how mammalian cell metabolism is adapted to support function, with a particular focus on the role metabolism plays in cancer. He uses mouse models to study how changes in metabolism impact all aspects of cancer progression with a goal of finding novel ways to exploit altered metabolism to help patients.

Vander Heiden earned a BS, an MD, and a PhD from the University of Chicago, and completed his clinical training in internal medicine and medical oncology at the Brigham and Women’s Hospital and the Dana-Farber Cancer Institute. After postdoctoral research at Harvard Medical School, Vander Heiden joined the faculty of the MIT Department of Biology and the Koch Institute in 2010. Among Vander Heiden’s awards and honors include a Burroughs Wellcome Fund Career Award for Medical Sciences, a Damon Runyon-Rachleff Innovation Award, a Stand Up To Cancer Innovative Research Grant, and being named a Howard Hughes Medical Institute Faculty Scholar.

From MSRP student to MIT professor
Justin Chen
March 13, 2017

The biology department welcomes Eliezer Calo back to MIT

By Justin Chen

 

As the newest faculty member of the MIT biology department, Eliezer Calo is working in Building 68, the same building where he was first inspired to become a scientist. Professor Calo’s relationship with MIT began eleven years ago when he was a chemistry major at the University of Puerto Rico with hazy career aspirations. Encouraged by his instructors to attend a Minority Access to Research Careers (MARC) conference, Calo came across a booth advertising the MIT Summer Research Program (MSRP). Even though Calo initially associated MIT with engineering and math, he applied for and received a summer internship position in Professor Stephen Bell’s lab studying DNA replication. “Experiencing the scope of MIT’s biological research and seeing how collaborative and enthusiastic people were about biology was eye opening,” Calo says. “That was the summer I decided to do a PhD.”

MSRP launched Calo’s scientific career and cemented his love for MIT. After graduating from the University of Puerto Rico, he returned to MIT’s biology department for graduate school and earned a PhD under the mentorship of Professor Jackie Lees. He then moved to Stanford University for postdoctoral training with Professor Joanna Wysocka. He began his faculty position at MIT in January and became an extramural member of the Koch Institute in March.

“We are thrilled to welcome Eliezer back to MIT as a faculty member,” says Biology Department head Alan Grossman. “He and the two other new faculty members, Professors Stefani Spranger and Sebastian Lourido, exemplify the energy and cutting edge research in the department. We eagerly anticipate many years of exciting discoveries from their labs.”

Now leading his own lab, Calo seeks to understand how cells assemble ribosomes and the roles they play in development and in disease. Ribosomes, intricate molecular machines, create building blocks of the body by translating the genome into proteins.  In order to sustain growth, human cells assemble millions of ribosomes. When defects in ribosome assembly occur during embryonic development, cells are unable to grow and divide, leading to developmental disorders.

One such disorder is Treacher Collins syndrome, which arises from a genetic alteration that impairs the expression of a gene named Treacle,whose protein product assists in ribosome assembly.  Surprisingly, although Treacle is expressed in most cells during early embryo development, the mutation affects only the nascent face: individuals have smaller facial bones making up their cheeks and jaws.

“Treacher Collins and other syndromes caused by abnormal ribosome assembly and function challenge our understanding of the ribosome,” Calo explains. “We think of ribosomes as constitutively expressed molecular machines required only for protein synthesis. These diseases, however, suggest that ribosomes might unexpectedly have very specific developmental roles as well.”

Describing how a single genetic mutation warps cell biology and triggers disease is a difficult task. In the case of Treacher Collins Syndrome, the precise mechanism remains unknown but scientists have identified two potential factors.  First, cells destined to become facial bones grow quickly during development and may be especially sensitive to reduced protein production. Second, new research suggests that Treacher Collins may also be caused by defective ribosomes activating cancer suppressor pathways, leading to slower cell division and cell death.

To design a simplified model of Treacher Collins syndrome, Calo has used CRISPR gene editing technology to introduce disease-relevant mutations into human embryonic stem cells in culture. The cells are then grown and differentiated into the specific facial tissues affected by Treacher Collins syndrome. These in vitro cell communities allow Calo to closely observe abnormalities as they arise during development and better understand how decreased protein levels, tumor suppressor pathways, or other factors yet to be discovered contribute to cell death.

To determine whether the results in cultured cells apply to whole organisms, Calo plans to validate his findings in zebrafish. Mutant zebrafish, like humans, have craniofacial defects and allow researchers to screen chemicals that may lessen facial anomalies. By working with human embryonic stem cells in culture and then testing the findings in zebrafish, Calo has created a powerful two-pronged approach to understand Treacher Collins and address fundamental questions of ribosome biology and disease.

As Calo establishes his new laboratory, he is also reprising a familiar role of instructor and mentor. While performing graduate research, he served as a teaching assistant for MIT’s introductory biology course (7.01) and as a program assistant for MSRP. Calo, who still runs into former students in New York, Boston, and Stanford, enjoys learning about their accomplishments and future goals. Now a professor, Calo will inspire the next generation of biologists by advising graduate students and MSRP researchers. “My MSRP experience shaped the course of my scientific career, so I look forward to having MSRP students working in my lab,” Calo says. “I want them to experience what it is like to do research at MIT.”

Posted: 12.5.17