Author: mantulin

New target for treating “undruggable” lung cancer

Drug already in clinical trials may be effective on some aggressive adenocarcinomas.

Becky Ham | MIT News correspondent
October 2, 2017

Mutations in the KEAP1 gene could point the way to treating an aggressive form of lung cancer that is driven by “undruggable” mutations in the KRAS gene, according to a new study by MIT researchers.

KEAP1 mutations occur alongside KRAS mutations in about 17 percent of lung adenocarcinoma cases. Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research and co-senior author of the study, and his colleagues found that cancer cells with nonfunctioning KEAP1 genes are hungry for glutamine, an amino acid essential for protein synthesis and energy use. Starving these cells of glutamine may thus offer a way to treat cancers with both KRAS and KEAP1 mutations.

Indeed, small-molecule-based inhibitors of glutaminase, an enzyme crucial to glutamine metabolism, slowed cancer cell growth and led to smaller tumors overall in human lung adenocarcinoma cell lines and in tumors in mice with KEAP1 mutations, the researchers found.

The study offers a way to identify lung cancer patients who might respond well to drugs that block the work of glutaminase, says MIT graduate student Rodrigo Romero, a first author on the paper that appears in the Oct. 2 online edition of Nature Medicine.

“All cell lines that we have currently tested that are KEAP1-mutant — independent of their KRAS status — appear to be exquisitely sensitive to glutaminase inhibitors,” says Romero, a graduate student in Jacks’ lab, who participated in the MIT Summer Research Program (MSRP) as an undergraduate.

Hyperactivating the antioxidant response

Lung adenocarcinoma accounts for about 40 percent of U.S. lung cancers, and 15 to 30 percent of those cases contain a KRAS mutation. KRAS has been “notoriously difficult to inhibit” because the usual ways of blocking the KRAS protein’s interactions or interfering with the protein’s targets have fallen short, says Romero.

Lung cancers containing KRAS mutations often harbor other mutations, including KEAP1, which is the third most frequently mutated gene in lung adenocarcinoma. To find out more about how these co-mutations affect lung cancer progression, the MIT research team created KEAP1 mutations in mouse models of lung adenocarcinoma, using the CRISPR/Cas9 gene-editing system to target the gene.

The KEAP1 protein normally represses another protein called NRF2, which controls the activation of an antioxidant response that removes toxic, reactive oxygen species from cells. When the researchers disabled KEAP1 with loss-of-function mutations, NRF2 was able to accumulate and contribute to a “hyperactivation” of the antioxidant response.

Lung adenocarcinomas bearing the KEAP1 mutation may “take advantage of this [hyper-activation] to promote cellular growth or detoxify intracellular damaging agents,” Romero says.

In fact, when the researchers examined genes targeted by NRF2 across a sample of human lung adenocarcinoma tumors, they concluded that the expression of these genes was greater in advanced stage IV tumors, and that patients with such “up-regulated” NRF2 tumors had significantly worse survival rates than other lung adenocarcinoma patients.

Tumors hungry for glutamine

Romero and colleagues used CRISPR/Cas9 to learn more about other genetic interactions with KEAP1 mutants. Their screening demonstrated that lung cancer cells with KRAS and KEAP1 loss-of function mutations were more dependent than other cells on increased amounts of glutamine.

To learn whether this glutamine hunger could be a therapeutic vulnerability, the researchers tested two glutaminase inhibitors against the cancer cells, including one compound called CB-839 that is in phase I clinical trials for KRAS-mutant lung cancer. CB-839 slowed growth and kept tumors smaller than normal in lung adenocarcinoma with KEAP1 mutations, the researchers found.

Phase I clinical trials that treat KEAP1-mutant lung adenocarcinoma patients with a combination of CB-839 and the cancer immunotherapy drug nivolumab (Opdivo) are also underway, says Romero, who notes the MIT study might help identify patients who would be good candidates for these trials.

“There are also many clinical trials testing the efficacy of glutaminase inhibition in a variety of cancer types, independent of KRAS status. However, the results from these studies are still unclear,” Romero says.

Jacks emphasizes that his laboratory has and will continue to study several mutations beyond KEAP1 that may cooperate with KRAS in their mouse models of human lung adenocarcinoma. “The complexity of human cancer can be quite daunting,” he notes. “The genetic tools that we have assembled allow us to create models of many individual subtypes of the disease and in this way begin to define the exploitable vulnerabilities of each. The observed sensitivity of KEAP1 mutant tumors to glutaminase inhibitors is an important example of this approach. There will be more.”

Co-authors on the Nature Medicine paper include former Koch Institute postdoc Thales Papagiannakopoulos, now at New York University, and MIT professor of biology Matthew Vander Heiden. The research was funded by the Laura and Isaac Perlmutter Cancer Support Grant, the National Institutes of Health, and the Koch Institute Support Grant from the National Cancer Institute.

Michael Rosbash PhD ’71 shares Nobel Prize in physiology or medicine

MIT alumnus and two others honored for discovering the molecular mechanisms of circadian rhythms.

Anne Trafton | MIT News Office
October 2, 2017

Michael Rosbash, who earned his PhD from MIT in 1971, will share the 2017 Nobel Prize in physiology or medicine, the Nobel Committee announced this morning in Stockholm.

Rosbash, now a professor of biology at Brandeis University, shares the prize with Jeffrey C. Hall of the University of Maine and Michael W. Young of Rockefeller University. The scientists were honored for “their discoveries of molecular mechanisms controlling the circadian rhythm.”

Circadian rhythms help living organisms adapt their biological activities to the normal 24-hour cycle of light and darkness. These rhythms influence behavior, sleep, metabolism, body temperature, and many other biological functions.

In 1984, Rosbash, Hall, and Young isolated a gene that regulates these daily rhythms in fruit flies. This gene, known as period, encodes a protein that accumulates during the night and is degraded during the day. Further work revealed that this protein inhibits the gene that encodes it, creating a negative feedback loop that is key to generating continuous oscillations.

Since then, the three scientists have discovered several other genes necessary for maintaining circadian cycles, and similar processes have been found in many other organisms, including humans.

Rosbash was born in Kansas City, Missouri, but grew up in Newton, Massachusetts. He earned his bachelor’s degree at Caltech before coming to MIT to pursue a PhD in biology. He has been on the faculty at Brandeis since 1974, and he is an investigator with the Howard Hughes Medical Institute and a member of the National Academy of Sciences. In 2013, Rosbash, Hall, and Young shared the Shaw Prize in Life Sciences and Medicine for their circadian clock research.

Rosbash is the 35th MIT alumnus to win a Nobel Prize, and the 88th MIT-connected winner of the prize.

Biologists identify possible new strategy for halting brain tumors

Cutting off a process that cancerous cells rely on can force them to stop growing.

Anne Trafton | MIT News Office
September 28, 2017

MIT biologists have discovered a fundamental mechanism that helps brain tumors called glioblastomas grow aggressively. After blocking this mechanism in mice, the researchers were able to halt tumor growth.

The researchers also identified a genetic marker that could be used to predict which patients would most likely benefit from this type of treatment. Glioblastoma is usually treated with radiation and the chemotherapy drug temozolamide, which may extend patients’ lifespans but in most cases do not offer a cure.

“There are very few specific or targeted inhibitors that are used in the treatment of brain cancer. There’s really a dire need for new therapies and new ideas,” says Michael Hemann, an associate professor of biology at MIT, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the study.

Drugs that block a key protein involved in the newly discovered process already exist, and at least one is in clinical trials to treat cancer. However, most of these inhibitors do not cross the blood-brain barrier, which separates the brain from circulating blood and prevents large molecules from entering the brain. The MIT team hopes to develop drugs that can cross this barrier, possibly by packaging them into nanoparticles.

The study, which appears in Cancer Cell on Sept. 28, is a collaboration between the labs of Hemann; Jacqueline Lees, associate director of the Koch Institute and the Virginia and D.K. Ludwig Professor for Cancer Research; and Phillip Sharp, an MIT Institute Professor and member of the Koch Institute. The paper’s lead authors are former MIT postdoc Christian Braun, recent PhD recipient Monica Stanciu, and research scientist Paul Boutz.

Too much splicing

Several years ago, Stanciu and Braun came up with the idea to use a type of screen known as shRNA to seek genes involved in glioblastoma. This test involves using short strands of RNA to block the expression of specific genes. Using this approach, researchers can turn off thousands of different genes, one per tumor cell, and then measure the effects on cell survival.

One of the top hits from this screen was the gene for a protein called PRMT5. When this gene was turned off, tumor cells stopped growing. Previous studies had linked high levels of PRMT5 to cancer, but the protein is an enzyme that can act on hundreds of other proteins, so scientists weren’t sure exactly how it was stimulating cancer cell growth.

Further experiments in which the researchers analyzed other genes affected when PRMT5 was inhibited led them to hypothesize that PRMT5 was using a special type of gene splicing to stimulate tumor growth. Gene splicing is required to snip out portions of messenger RNA known as introns, that are not needed after the gene is copied into mRNA.

In 2015, Boutz and others in Sharp’s lab discovered that about 10 to 15 percent of human mRNA strands still have one to three “detained introns,” even though they are otherwise mature. Because of those introns, these mRNA molecules can’t leave the nucleus.

“What we think is that these strands are basically an mRNA reservoir. You have these unproductive isoforms sitting in the nucleus, and the only thing that keeps them from being translated is that one intron,” says Braun, who is now a physician-scientist at Ludwig Maximilian University of Munich.

In the new study, the researchers discovered that PRMT5 plays a key role in regulating this type of splicing. They speculate that neural stem cells utilize high levels of PRMT5 to guarantee efficient splicing and therefore expression of proliferation genes. “As the cells move toward their mature state, PRMT5 levels drop, detained intron levels rise, and those messenger RNAs associated with proliferation get stuck in the nucleus,” Lees says.

When brain cells become cancerous, PRMT5 levels are typically boosted and the splicing of proliferation-associated mRNA is improved, ultimately helping the cells to grow uncontrollably.

Predicting success

When the researchers blocked PRMT5 in tumor cells, they found that the cells stopped dividing and entered a dormant, nondividing state. PRMT5 inhibitors also halted growth of glioblastoma tumors implanted under the skin of mice, but they did not work as well in tumors located in the brain, because of the difficulties in crossing the blood-brain barrier.

Unlike many existing cancer treatments, the PRMT5 inhibitors did not appear to cause major side effects. The researchers believe this may be because mature cells are not as dependent as cancer cells on PRMT5 function.

The findings shed light on why researchers have previously found PRMT5 to be a promising potential target for cancer treatment, says Omar Abdel-Wahab, an assistant member in the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center, who was not involved in the study.

“PRMT5 has a lot of roles, and until now, it has not been clear what is the pathway that is really important for its contributions to cancer,” says Abdel-Wahab. “What they have found is that one of the key contributions is in this RNA splicing mechanism, and furthermore, when RNA splicing is disrupted, that key pathway is disabled.”

The researchers also discovered a biomarker that could help identify patients who would be most likely to benefit from a PRMT5 inhibitor. This marker is a ratio of two proteins that act as co-factors for PRMT5’s splicing activity, and reveals whether PRMT5 in those tumor cells is involved in splicing or some other cell function.

“This becomes really important when you think about clinical trials, because if 50 percent or 25 percent of tumors are going to have some response and the others are not, you may not have a way to target it toward those patients that may have a particular benefit. The overall success of the trial may be damaged by lack of understanding of who’s going to respond,” Hemann says.

The MIT team is now looking into the potential role of PRMT5 in other types of cancer, including lung tumors. They also hope to identify other genes and proteins involved in the splicing process they discovered, which could also make good drug targets.

Spearheaded by students and postdocs from several different labs, this project offers a prime example of the spirit of collaboration and “scientific entrepreneurship” found at MIT and the Koch Institute, the researchers say.

“I think it really is a classic example of how MIT is a sort of bottom-up place,” Lees says. “Students and postdocs get excited about different ideas, and they sit in on each other’s seminars and hear interesting things and pull them together. It really is an amazing example of the creativity that young people at MIT have. They’re fearless.”

The research was funded by the Ludwig Center for Molecular Oncology at MIT, the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the National Institutes of Health, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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.

New faculty welcomed to Department of Biology

Assistant professors Joey Davis and Rebecca Lamason will spearhead research initiatives into fundamental cellular processes.

Raleigh McElvery | Department of Biology
September 11, 2017

MIT’s Department of Biology is welcoming two new assistant professors, Joey Davis and Rebecca Lamason, this September. The duo will augment the department’s efforts in basic research, probing fundamental facets of cellular processes like molecular degradation and bacterial infection.

“I am thrilled that Becky and Joey have joined our department,” says Alan Grossman, department head. “They bring new research areas and approaches that fit well with our overarching goals to help solve fundamental biological problems. I anticipate that their expertise and interests will enable collaborations within MIT and beyond.”

The arrival of Davis and Lamason brings the number of recent biology faculty additions to five since January.

Joey Davis

Joey Davis investigates how cells maintain a delicate internal balance of assembling and dismantling their own machinery, particularly macromolecules. A cell’s ability to keep the precarious balance of this process in check often diminishes with age, and when it goes awry, disease can ensue.

Born in Durango, Colorado, but raised in Long Beach, California, Davis became interested in how things were built by emulating his construction worker father. Assembling bicycles and other objects spurred Davis’ curiosity about the nuts and bolts of the natural world and he soon realized that, unlike bikes, biological systems were not so easily parsed.

Davis went on to earn dual bachelor’s degrees in biological engineering and computer science from the University of California at Berkeley. He arrived at MIT as a graduate student shortly thereafter, jointly advised by professors Robert Sauer and Tania Baker, both of whom are based in Building 68, where Davis will now run his own lab. He also served as a teaching assistant for 7.51 (Principles of Biochemical Analysis), and as an advisor to MIT’s team for the International Genetically Engineered Machines (iGEM) competition.

Davis became enthralled by molecular disassembly, particularly in bacteria. After a brief foray into the biotechnology sector, he returned to his California roots to pursue his postdoctoral training at the Scripps Research Institute in La Jolla. He brought with him his MIT-inspired fervor for large cellular machinery, and in doing so encountered his macromolecule of choice: the ribosome. Sometimes referred to by researchers as the “construction workers” of cells, ribosomes play a key role in building molecules from genetic blueprints. After three years, he was awarded a K99/R00 Pathway to Independence Award from the National Institute of Aging, which included an affiliation at the Sanford Burnham Prebys Medical Discovery Institute. The award will also help fund his first several years of research at MIT.

In his own lab, Davis seeks to determine how cells assemble and destroy ribosomes and other macromolecules, as well as how they remove harmful protein aggregates and dysfunctional organelles. These functions are often compromised due to age, genetic mutations, and environmental stresses, leading to diseases like cancer, diabetes, and neurodegenerative disorders. Davis says he is excited to further examine these processes at MIT.

“The questions I’m asking about how the degradation system is constructed and how it targets substrates are similar to those I pursued in graduate school — but the answers will likely be completely different,” Davis says. “The members of the MIT research community truly want to know how the natural world works, and that mindset draws me in today as much as it did 13 years ago.”

Davis has been hard at work developing a series of new research techniques, some involving cryo-electron microscopy, a method to image large macromolecules at high resolution. His discoveries could ultimately assist pharmaceutical development — improving antibiotics and anti-cancer therapeutics — and perhaps enabling scientists to one day engineer their own bigger and better molecules.

Rebecca Lamason

Rebecca Lamason investigates what happens when cellular functions are hijacked by unwanted interlopers — namely, the bacteria that cause diseases such as spotted fever and meningitis. Her interdisciplinary work spans multiple fields, including immunology, genetics, biochemistry, cell biology, and microbiology.

Growing up in a family that was interdisciplinary in its own right, composed of both artists and mechanics, Lamason has always sought to examine fundamental questions from multiple perspectives.

After earning a bachelor’s degree in molecular biology from Millersville University in Pennsylvania, she went on to graduate school at the Johns Hopkins University School of Medicine, where she immersed herself in the field of immunology. There she demonstrated how a molecule called CARD11 regulates immune cell activation, a discovery with potential applications for cancer therapeutics. She also served as a teaching assistant for the school’s graduate immunology course and co-founded the Immunology Student Journal Club.

It wasn’t until her postdoctoral training at the University of California at Berkeley, however, that Lamason found her model systems: two species of bacteria called Rickettsia parkeri and Listeria monocytogenes.

The two pathogens lay siege to cells in much the same way, entering and leveraging preexisting internal structures to build tails for rapid migration to neighboring cells. Lamason hypothesized that to do so, the intruders must also take over the complex communication systems between cells. Common scientific consensus held for years that Rickettsia, Listeria, and several other species of bacteria spread in a similar manner — using their tails to propel themselves and ram into the host’s cell wall to gain access to neighboring cells. Lamason, however, demonstrated this isn’t always the case and that Rickettsia tend to lose their tails and must then rely on the host cell’s internal machinery instead to invade neighboring cells.

Lamason was drawn to MIT by the diverse array of research efforts that are unified by a collaborative desire to explore the mechanistic details of cellular systems. Like Davis, she received a K99/R00 Pathway to Independence Award in 2015 — in her case from the National Institute of General Medical Sciences. Her lab will continue to investigate the interplay between invasive bacteria and their hosts, aiming to clarify how cell-to-cell spread varies between species. She plans to leverage advanced imaging platforms with tools from cell biology, microbiology, genetics, and biophysics to gain a deeper understanding of how these pathogens manipulate their hosts.

“My goal is to understand this virulence mechanism in order to prevent disease, and to use pathogens as tools to better understand host cell biology,” Lamason says. “This type of study lends itself naturally to interdisciplinary work. I love the challenge of learning new things and using multiple approaches to clarify important biological questions.”

Gene Brown, professor emeritus of biology, dies at 91

A pioneer in the field of intermediary metabolism and former dean of the School of Science, Brown’s deepest passion was teaching.

Vivian Siegel | Department of Biology
August 18, 2017

Gene M. Brown, MIT professor emeritus of biology, former department head, and former dean of the School of Science, passed away on Aug. 4 at the age of 91.

“He was really the heart and soul of the department for a very long time, devoted to undergraduates and to teaching,” says MIT Professor Lisa Steiner. Steiner, an expert in the evolution and development of the immune system, was hosted by Brown during her recruitment visit to MIT and became the first female faculty member hired in the Department of Biology. “The idea of the department without him is quite shocking.”

A pioneer in the field of intermediary metabolism, Brown’s research career focused on how living systems carry out chemical reactions in order to survive. He trained himself in enzymology after arriving at MIT, and he and his students and postdocs focused primarily on the enzymatic synthesis of several B vitamins, including thiamine, folic acid, riboflavin, and coenzyme A. He is best known for his work on the biosynthesis of folic acid and related compounds both in microorganisms and in the fruit fly Drosophila melanogaster, publishing over 100 research papers in his career.

“Gene was a wonderful research advisor and teacher,” says Linda Spremulli, professor emerita of chemistry at the University of North Carolina at Chapel Hill, who was a graduate student with Brown from 1969 to 1973. “He transformed my life, instilling in me a love for the beauty of metabolic pathways with their complex mechanisms.”

Growing up in rural Missouri and Idaho, Brown was the first member of his family to finish high school, and the only person in his graduating class to attend college. After a year as a college student in Idaho, Brown enlisted in the Army Air Forces, where he taught defensive measures against chemical warfare. After his term in the Army Air Forces, he returned to college at Colorado A & M College, where he majored in chemistry, graduating in 1949. He completed his graduate work at the University of Wisconsin in 1953 under the direction of Esmond Snell, isolating and characterizing the enzymatic synthesis of pantetheine, an analog of vitamin B5, and an intermediary in the production of coenzyme A.

Brown continued working with Snell as a postdoc at the University of Texas until he was recruited by Professor Jack Buchanan to join the newly forming biochemistry division of the MIT Department of Biology in 1954. Brown served as executive officer of the department from 1967 to 1972; as associate department head under Professor Boris Magasanik from 1972 to 1977; as department head from 1977 to 1985; and as dean of the School of Science from 1985 to 1991. While serving as dean of science, Brown closed his research program. He officially retired from MIT in 1996, but continued teaching until 2014.

Brown’s deepest passion was teaching. “As dean, he would leave meetings with the president of MIT to go teach,” recalls Professor Tom RajBhandary, who co-taught 7.05 (Introductory Biochemistry) with Brown for over 20 years. He was legendary for teaching intermediary metabolism without any notes, filling the boards of Room 10-250 with detailed pathways in meticulous handwriting. Brown got his first taste of teaching in high school, when his math and chemistry teachers would routinely call him to the board to explain the material. He was the first person in the Department of Biology to give open book and open note examinations, promoting the view that students should not have to memorize, but rather should be assessed for their ability to think and to solve problems. He was involved in teaching 7.05 for 60 years.

“I loved teaching with Gene and will miss him,” says Professor Matthew vander Heiden, who currently teaches 7.05. “The privilege to see how he taught the class has had a tremendous impact on my own approach to teaching. I think he would be pleased to know that the unique insights he provided continue to be passed on each spring, and will continue to be passed on as long as I am involved in the course.”

Teaching undergraduates was a value that extended throughout his career. As dean of science, he made it clear that the quality of teaching would be an important consideration for tenure decisions. He also co-chaired the committee that instituted the undergraduate communications requirement aimed at improving skills in both written and oral communications. The Department of Biology gives two teaching awards in his honor: The Gene Brown Prize, funded by Brown himself, recognizes teaching excellence among undergraduates; and the Gene Brown-Merck Teaching Award, funded by Merck and by Brown’s former graduate students and postdocs, recognizes teaching excellence among graduate students.

During Brown’s administrative tenure in biology, the MIT Center for Cancer Research (the predecessor of the Koch Institute for Integrative Cancer Research) and the Whitehead Institute were established with Department of Biology faculty leadership (Professor Salvador Luria for the Center for Cancer Research in 1974, and Professor David Baltimore for the Whitehead Institute in 1982).

A longtime resident of Concord, Massachusetts, Brown is survived by his children, James, Lindsey, and Holly, and his four grandchildren. He was predeceased by his wife, Shirley, and a brother, James.

Gifts in Brown’s name may be made to the Gene Brown Undergraduate Education Fund, fund No. 3839399. Donations in his memory will support undergraduates and undergraduate education in the MIT Department of Biology. For more information, contact Rebecca Chamberlain at 617-253-4729 or rchambe@mit.edu.

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.”

A rose by any other name would smell as yeast

Emily Havens Greenhagen ’05 leads a team of scientists brewing perfume from yeast.

Justin Chen | Department of Biology
July 14, 2017

From afar, the multistory fermenters — towering metal cylinders encompassed by scaffolding, ladders, and pipes — look like rockets on a launch pad. Climbing to the top of the fermenter, visitors to the Mexico City manufacturing plant can peer down at a set of paddles churning 50,000 liters of frothy, golden broth. Within the mixture, genetically engineered yeast are synthesizing lactones — a family of molecules responsible for the aromas of fruits and flowers. MIT Department of Biology alumna Emily Havens Greenhagen ’05 has visited the plant over several weeks to monitor her company’s most promising project: a plan to make perfume from yeast cells.

Greenhagen is director of fermentation engineering at Ginkgo Bioworks, a Boston-based synthetic biology company seeking to turn microbes into customizable factories to produce products ranging from pesticides to perfumes. Scientists such as Greenhagen know that microbes can manufacture organic products more efficiently than any machine or production line. Instead of workers at an assembly line, yeast cells use enzymes — proteins that perform a specific task such as removing or adding a group of atoms to a molecule. Working together, teams of enzymes incrementally transform basic nutrients like sugar into other compounds such as alcohol and carbon dioxide. “By inserting DNA encoding for enzymes from different plants or animals into yeast cells,” Greenhagen says, “we can tailor microbes to produce different materials.”

Manipulating yeast cells is an old idea. For hundreds of years, people have been brewing beer through fermentation, a natural process where yeast consume sugar to create alcohol and different flavorings. In the 1930s, scientists began using microbes to create antibiotics and biofuels. “What makes Ginkgo cutting edge is the automation and scale,” Greenhagen explains of the company co-founded in 2008 by synthetic biologist Tom Knight ’69, SM ’79, PhD ’83. “Using robots, we can genetically modify hundreds of yeast strains and test how they perform in just one week.”

Ginkgo Bioworks’ automation played a critical role in creating the yeast strain that Greenhagen observed in the Mexico City manufacturing plant. These microbes, containing a set of enzymes needed to turn fatty acids into lactones, were engineered through thousands of trial-and-error experiments performed by robots. For each enzyme encoded in the final strain, a team of scientists and machines led by Greenhagen had tested hundreds of versions originating from diverse plant species and strategically mutated in different ways to work more efficiently in yeast cells.

During the testing process, researchers grew thousands of yeast strains, each genetically engineered for a single enzyme, in small tabletop fermenters before combining the most effective genetic modifications into a single cell to produce lactones. Ten years ago, when Greenhagen first started in industry, fermenting was a labor-intensive process done by hand, requiring a single researcher to manage four reactors at a time. In contrast, members of Greenhagen’s team — using robots to mix different concentrations of nutrients, add yeast extract, and monitor the output of desired molecules — routinely managed 24 experiments simultaneously. As a result of automation, the development process took six months instead of a year and half. After a purification process, the developed scent could then be delivered to Robertet, a French fragrance and flavor manufacturer and Ginkgo’s first commercial customer. “The robots don’t just speed up projects,” Greenhagen says, “they take care of the monotonous tasks so that we have more time to think about results and design new experiments — the fun stuff that scientists really want to do.”

Like Ginkgo Bioworks, Greenhagen embodies the convergence of biology and engineering. As a freshman at MIT, Greenhagen had decided to pursue chemical engineering but changed her plans when she learned about synthetic biology. “I couldn’t stop reading my textbook,” she recalls. “I was so excited by the idea that there are living organisms that we can modify to use as tools. That’s when I decided to become a scientist.”

Greenhagen credits one particular microbiology course, taught by Professor Graham Walker, for shaping her thinking as a biologist. While lecturing on organelles, Walker encouraged students to imagine the room as a cell and to point out where the nucleus or mitochondria might be located. “His teaching style inspired me to really visualize what’s going on in the fermentation vessel,” Greenhagen says. “Whereas fermentation engineers worry more about physical variables like oxygen transfer and think of organisms as black boxes, my training at MIT gave me an empathy for microbes. It’s an approach that a lot of chemical engineers don’t necessarily think about and has been key to my success.”

By harnessing biology and engineering, Greenhagen and others in the field of synthetic biology are beginning to transform manufacturing. Many consumer goods, from food to clothes to perfume, are produced using traditional ingredients and industrial processes that are increasingly unsustainable as planetary resources dwindle. By using microbes, companies can generate many of the raw resources they require with less energy and waste than factories.

In the case of flavors and fragrances, companies like Robertet had been extracting the majority of their starting compounds from plants and flowers, whose growth may vary dramatically from year to year. In contrast, Ginkgo Bioworks’s yeast feed on basic crops like corn and sugar cane, which are more economical to raise, and release their products in highly reliable reactions. Encouraged by its success with perfumes, Ginkgo Bioworks is using similar approaches to make organic pesticides, industrial enzymes, and products for human health.

For Greenhagen, scented yeast represent not only the potential of synthetic biology but also the culmination of years of work and education. Before joining Ginkgo Bioworks, Greenhagen had spent six years at another startup without seeing any of her projects commercialized. “When we were bought out by a larger company and taken off the commercialization path, I was told to sit back and relax but that’s not what I do,” she says.

Greenhagen traces her driving mentality back to MIT lab courses and an Undergraduate Research Opportunities Program (UROP) project in Professor Leona Samson’s laboratory. There, Greenhagen says, students were expected to read papers, design their own experiments, and place their findings in the context of published results. “This critical thinking and problem solving combined with real-life experience inspired me to think of my education as a gift that I should put to use,” she says. Years later, having traveled thousands of miles to see her first commercialized product, Greenhagen says she is still moved by MIT. “When I walk through campus, I get goosebumps from all the memories. It is such an amazing place.”

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.

STEX event showcases innovations in fitness technology and science

Entrepreneurs, researchers, and industry experts build connections at workshop.

Rob Matheson | MIT News Office
June 26, 2017

Many MIT-affiliated startups are innovating in the burgeoning fitness technology and science space, aiming to promote healthier lifestyles and help optimize athletic performance.

Novel products from these startups include a smart chair that fights back pain and diabetes, a sleeve that monitors muscle-movement data that users can share in the cloud, a wristband that tracks blood oxygen levels for greater performance, and even a so-called anti-aging pill.

A workshop hosted June 22 by the MIT Office Corporate Relations’ (OCR) MIT Startup Exchange (STEX) program brought together some of these MIT entrepreneurs and industry experts to showcase their innovations and foster connections that could lead to new business opportunities.

Held throughout the year, the three-hour STEX workshops include lightning presentations from MIT-connected startups; brief talks from academic innovators, industry experts, government representatives, and venture capitalists; startup presentation and demonstration sessions; and an interactive panel discussion.

At last week’s event, eight entrepreneurs pitched their fitness-tech products — several rooted in MIT research — to a crowd of around 80 entrepreneurs, researchers, and industry experts in the OCR headquarters on Main Street, in Cambridge, Massachusetts. The academic keynote speaker was MIT Novartis Professor of Biology Leonard Guarente, who took the opportunity to demystify the science behind his startup Elysium Health’s “anti-aging pill,” which is made of compounds that aim to thwart age-related cell damage, which can lead to inflammatory and heart diseases, osteoporosis, and diabetes.

STEX events aim to stimulate discussion, foster collaboration, and build partnerships between MIT-connected startups and member companies of MIT’s Industrial Liaison Program (ILP). The series covers a broad range of topics: a recent workshop focused on energy storage, while upcoming events will focus on synthetic biology, robotics and drones, cancer therapies, renewable energy, world water issues, and 3-D printing.

“Fitness, wellness and nutrition are very exciting areas, and MIT founders are very active in the space. We certainly have industry coming to campus interested in all of these technologies and products coming from them,” Trond Undheim, who directs STEX and is the organizer of the event, said in his opening remarks.

Presenter Simon Hong, a researcher in the McGovern Institute for Brain Research at MIT, and CEO of smart-chair startup Robilis, said last week’s STEX workshop provided “an opportunity to interact with potential stakeholders.”

Based on neuroscience research, Robilis developed StandX, a chair with two automated moving halves, side by side. The halves alternate — one dropping down and the other staying straight — making the user sit down on one half while standing on the opposite leg. The frequent alternation prevents stress on the spine caused by sitting in one position for extended periods, and the chair’s design encourages proper posture. The movement also interrupts prolonged sitting, which is associated with diabetes.

During a startup demonstration session midway through the event, Hong’s station was crowded with attendees looking to try out the chair. In the end, he walked away with a few contacts interested in helping with production and in introducing him to potential investors. “I was quite satisfied with the event,” Hong told MIT News. “It is in a way a networking event, and good things tend to happen quite unexpectedly during many, many interactions with people.”

Apart from providing a venue to spread the word about his wearables, the event enabled Alessandro Babini MBA ’15, co-founder of Humon, to connect with larger organizations in the space. Humon, a wearable targeted at endurance athletes, attaches to a muscle, where it monitors blood oxygen levels by shining a light into the skin and analyzing changes in the light that indicate less or more oxygen.

“It was interesting to get an understanding about what big brands seek in partners, what they’re looking to invest in, and what they’re working on now,” Babini told MIT News. “Big corporations have a lot of customers and a big influence on where the market is going.”

Another interesting MIT spinout, figure8, presented a wearable that captures 3-D body movement that can be analyzed by the user or shared with an online community — like a “YouTube” of movement data.

The wearable is a small sleeve made from novel sensor-woven fabric that fits over the arm or leg to track joint and muscle movement. It lets users map the movement of muscle, bone, and ligaments. Put on a knee, for instance, the wearable can map individual ligaments, which is valuable for, say, monitoring the anterior cruciate ligament (ACL). One application is in physical therapy, so athletes can track injuries as they heal.

Users can also map their movement to others. Dancers, for instance, can use the sensor to match their movements to those of others during training. The startup is also developing a platform that lets users upload and share that data in the cloud.

“Before YouTube, no one thought about video as something you can share, upload, and download as a commodity,” said co-founder and CEO Nan-Wei Gong, an MIT Media Lab researcher, during her presentation. “We’re trying to create a system for everyone to collect this motion [data] they can upload and download.”

Other startups that presented included: Kitchology, Fitnescity, Digital Nutrition, Food for Sleep, and SplitSage.

In his keynote, Guarente explained the science and history behind Elysium’s “anti-aging” pill, called Basis, which he himself has been taking for three years. He noted the pill doesn’t necessarily make people feel more youthful or healthier, especially if they’re already healthy. “You should just fall apart more slowly,” Guarente said to laughter from the audience.

Years ago, Guarente and other MIT researchers identified a group of genes called sirtuins that have been demonstrated to slow the aging process in microbes, fruit flies, and mice. For instance, calorie-restricted diets, long known to extend lifespans and prevent many diseases in mammals, is key in activating sirtuins. “It turns out there are compounds that can do the same thing,” Guarente said.

It was later discovered that one of those compounds is abundant in blueberries and that an enzyme called nicotinamide adenine dinucleotide (NAD) is essential in carrying out the activity of sirtuins. But NAD deteriorates with age. “If there’s not enough NAD, you don’t activate sirtuins. Metabolism and DNA-repair goes awry, and a lot of things go wrong,” he said.

However, in the NAD synthesis pathway, NAD’s precursor, called nicotinamide riboside (NR), can be injected into an organism, where it would move efficiently into cells and be converted into NAD.

Basis is a combination of NR and the sirtuin-activating compound from blueberries.

Last year, Elysium conducted a 120-person trial. The results indicated that the pills were safe and led to an increase and sustainability of NAD levels. More trials are on the way, and the startup is growing its pipeline of products. It has not yet been shown whether Basis can extend life-span in humans.

“We could really make a difference in people’s health,” Guarente said at the conclusion of his talk. “And it would add to all the … medical devices and DNA analysis and motion sensors, so that people can begin to do what they want to do, which is to take charge of their health.”

The investor speaker was David T. Thibodeau, managing director of Wellvest Capital, an investment banking company specializing in healthy living and wellness. The industry speaker was Matthew Decker, global technical leader in the Comfort and Biophysics Group of W.L. Gore and Associates, the manufacturing company best known for Gore-Tex fabrics.

Panelists were Guarente, Decker, Thibodeau, and Josh Sarmir, co-founder and CEO of SplitSage, an MIT spinout that is developing an analytics platform that can detect “sweet spots” and “blind spots” in people’s fields of vision to aid in sports performance, online advertising, and work safety, among other applications.

STEX has a growing database of roughly 1,200 MIT-affiliated startups. Last year, OCR, in close partnership with ILP, created STEX25, an accelerator for 25 startups at any time that focuses on high-level, high-quality introductions. The first cohort of 14 startups have gone through the accelerator, gaining industry partnerships that have led to several pilots, partnerships, and lead client relationships.