Broad Institute of MIT and Harvard

Learn more about how stem cells are helping scientists understand psychiatric disorders in a new Q&A with Ralda Nehme, director of Broad’s stem cell program. Nehme has established the Stanley Center’s Stem Cell Resource, which holds frozen cell lines from about 1,000 donors with a range of diagnoses and ancestral backgrounds. Scientists can use these cells to generate different cell types that more faithfully model human disease than animal cell lines.

“The possible applications are almost limitless,” Nehme said.

broad.io/QA-Ralda-2024

Our researchers have built AI models that predict potential toxic effects of drugs before they are tested in humans. These tools were trained on FDA-curated data and while they won’t replace traditional testing, promise to help better guide research and make drug development more efficient.

broad.io/drugdiscovery-0724

Seramount has recognized the Broad Institute as one of its 100 Best Companies, for the seventh time, recognizing Broad’s ongoing commitment and leadership in the areas of paid time off and leaves, benefits and work-life programs, and workplace best practices. Learn more about why Broad earned a spot on this year’s list at https://bit.ly/4cCajDh

A new study from Broad and Massachusetts General Hospital Cancer Center researchers, Robert Manguso, Nabeel El-Bardeesy, and Meng-Ju Wu, in Science Magazine finds cancer drugs inhibiting IDH1 production lead to the expression of ancient viral particles, triggering an antiviral response that kills tumor cells.

These drugs are approved for certain brain and liver tumors, as well as myeloid leukemias, and the discovery suggests methods to enhance the efficacy of the mIDH1 inhibitors and potential applications to similar cancers.

broad.io/IDH1-news

Brain organoids are a powerful platform for modeling the cellular impacts of genetic variants on the brain. They are typically constructed using cells from single donors, but Noelia Antón-Bolaños, Irene Faravelli, Paola Arlotta, and collaborators from the Stanley Center for Psychiatric Research and the Klarman Cell Observatory have developed a new generation of brain organoids that incorporate cells from multiple people. These brain "chimeroids" can help researchers study the influence of individuals' genetic background on the brain's cellular responses to toxic exposures, disease-associated variants, and potential therapeutic compounds.

https://www.broadinstitute.org/news/brain-chimeroids-offer-window-relationships-between-genetics-and-exposures

Researchers at Whitehead Institute and Broad Institute have developed a gene-silencing tool, CHARM, that turns off the gene causing prion diseases and could pave the way for new gene therapies for these fatal conditions. In mice, the epigenetic editing technology eliminated more than 80% of the prion protein in the brain. Read more about the journey from research to potential therapy.

https://www.broadinstitute.org/news/therapy-candidate-fatal-prion-diseases-turns-disease-causing-gene

Research over the last decade has found links between the gut microbiome and risk for type 2 diabetes, which affects half a billion people worldwide. In the largest and most diverse study yet of the microbiome and type 2 diabetes, a Brigham and Women's Hospital, Harvard T.H. Chan School of Public Health, and Broad team found that the presence of specific viruses and genetic variants within bacteria correspond with T2D risk.

https://www.broadinstitute.org/news/gut-microbiome-changes-fuel-increased-risk-type-2-diabetes

New research shows that an important part of CRISPR screens called CRISPR guides do not perform equally well in cells from people of all ancestries, which could cause experiments to miss potential new drug targets.
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“CRISPR is used ubiquitously in preclinical research, but only a minority of researchers are thinking carefully about the specific germline and ancestries that relate to their model systems,” said Jesse Boehm, a co-senior author on the study recently published in Nature Communications. “This is a warning call for the community that functional genomics is not immune to ancestry bias, and a source of opportunity to look more closely at this kind of data.”

Some CRISPR screens may be missing cancer drug targets Current CRISPR guides don’t work equally well in cells from people of all ancestries, which could lead to false negative results.

Originally from Beirut, Lebanon, Moe Haines came to the U.S. thinking he would study pharmacy but found his true calling in biochemistry after being inspired by his college biology and chemistry courses.

Now, as a senior research associate in our Proteomics Platform, Moe leverages advanced mass spectrometry to study proteins involved in cancer. His work is critical to the Platform’s collaboration with the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC), where he helps develop new methods for analyzing proteins in samples from cancer patients at scale. Learn more about Moe and his journey in this Q&A.

#WhyIScience Q&A: A biochemist uses mass spectrometry to find proteins involved in cancer Moe Haines talks about how his open-minded approach to science led him to pursue a career in proteomics.

A new version of the gene-editing approach called prime editing is now capable of inserting or substituting entire genes in human cells at therapeutic levels.

The advance, from the lab of Broad core institute member David Liu, could one day help researchers develop a one-size-fits-all gene therapy for diseases such as cystic fibrosis that are caused by one of hundreds or thousands of different mutations in a gene. Using this new approach, they could insert a healthy copy of the gene at its native location in the genome, rather than having to create a different gene therapy to correct each mutation using other gene-editing approaches that make smaller edits.

Improved prime editing system makes gene-sized edits in human cells at therapeutic levels The gene-editing approach uses prime editors and evolved enzymes called recombinases, and could pave the way to effective one-size-fits-all gene therapies for diseases such as cystic fibrosis.

Broad is turning 20!

Join us virtually on Wednesday, June 5 at 3:00 pm ET for "Origin Stories: How Broad’s earliest days sparked two decades of innovation." Hear from David Altshuler, Stacey Gabriel, Todd Golub, Eric Lander and more as they recount the pioneering work that launched the Broad Institute and the culture of collaboration that drives our community today.

The livestream is free and open to the public. Register: https://broad.io/June5

Thank you to everyone who joined us for our recent Broad Discovery Series event, “Moving from "hit-or-miss" toward a brighter future for psychiatric diagnosis and care.”

The panel discussion focused on the topic of mental health and the challenges faced in psychiatric diagnosis and care. Key themes that emerged from the conversation were the importance of support and community, the need for more objective and early diagnoses, the role of genetics in understanding mental illness, and the potential for personalized and holistic treatment approaches. Our panelists emphasized the need for inclusivity and diversity in research and the importance of hope in driving progress.

Also highlighted was the significance of lived experiences in shaping research direction and the value of advocacy groups like NAMI in supporting individuals and influencing research. Overall, the discussion emphasized the ongoing efforts to improve mental health care and the potential for advancements in the field.

A big thank you to our panelists: Francis Burnett, Aidan McKee, Benjamin Neale, and Susanne Jakob for a hybrid hour-long discussion, and our moderator Monica Luke.

Watch: https://www.youtube.com/watch?v=ik3MdsNBSOQ

Gene therapy could potentially treat a range of severe genetic brain disorders, which currently have no cures and few treatment options. But FDA-approved forms of the most commonly used vehicle for packaging and delivering these therapies to target cells, adeno-associated viruses (AAVs), aren’t able to efficiently cross the blood-brain barrier and deliver cargo.

Now, from the Deverman Lab comes an important step toward gene therapy for brain diseases: the first published AAV that targets a human protein and reaches the brain in humanized mice. Because the vehicle binds to a well-studied human target, the scientists say it has a good chance at working in patients.

New gene delivery vehicle shows promise for human brain gene therapy Scientists have engineered an adeno-associated virus (AAV) that efficiently crosses the blood-brain barrier in human cell models and delivers genes throughout the brain in humanized mice.

The Genetics of Eating Disorders study This study has the potential to expand knowledge of the genetic risk factors underlying eating disorders using large-scale data and sample collection, so that future progress in research and therapeutics can be applicable to and better serve a diverse population. The Genetics of Eating Disorders stu...

Help us kick-off our 2024 tour season with a visit to two of Boston’s coolest STEM museums — one of which isn’t usually open to the public!
https://bit.ly/3Um7rmq
Our opening weekend of Innovation Trail tours celebrates the incredible STEM museums of Boston and Cambridge. No other city has so many STEM-focused museums within walking distance of each other. On this tour, we’ll get you inside the Verizon Museum, not typically open to the public. Then, we’ll walk together and discuss several other key places on The Innovation Trail, before wrapping up at Mass. General Hospital’s Museum of Medical History and Innovation. And did we mention you’ll receive our limited edition Innovation Trail baseball cap!?

The Merkin Prize in Biomedical Technology is awarded to F. William Studier for the development of a widely used protein- and RNA-production platform. The $400,000 award recognizes the far-reaching medical impacts of Studier’s development, in the 1980s, of an efficient and scalable technology to produce mass amounts of RNA and proteins in laboratories that is widely used today all over the world.

https://www.broadinstitute.org/news/merkin-prize-biomedical-technology-awarded-f-william-studier-development-widely-used-protein

When Liz Martin took up crew at the suggestion of her parents in high school, she wasn’t sure she’d keep up with the sport because she didn’t want it to conflict with her academics. More than ten years later, Liz has rowed in the US Olympic trials and won the Head of the Charles regatta and is now a computational biologist in the Getz Lab, where she balances elite rowing and a career in cancer biology.

“If you’re rowing together, you have to find a way to compromise, and that gets magnified when you are sitting in a boat and you have to do everything together at the same time or else nothing works,” she said. “That’s important in the workplace as well.”

Read more about the parallels between science and being out on the water and what it’s like to row in Boston in a new Q&A.

#WhyIScience Q&A: How a computational biologist balances work with life as an elite rower Liz Martin reflects on how her career in cancer biology complements her intense training on the water.

Exercise lowers the risk of many diseases, but scientists still don’t fully understand how exercise changes the body on a molecular level. Most studies have focused on a single organ, s*x, or time point, and only include one or two data types.

New research shows that the body’s response to exercise is more complex and far-reaching than previously thought. In a study on rats, a team of scientists from across the United States has found that physical activity causes many cellular and molecular changes in all 19 of the organs they studied in the animals.

Scientists work out the effects of exercise at the cellular level Prolonged physical activity in rats results in profound changes to RNA, proteins, and metabolites in nearly all tissues, providing clues to many human health conditions.

After Ebola struck West Africa in 2014, Pardis Sabeti and Christian Happi began imagining a new model of pathogen surveillance. Their vision: a network of experts and diagnostic and sequencing centers in Africa that would act as sentinels, quickly detecting and reporting local clusters of viral infections before they morphed into larger outbreaks.
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Read more about the beginnings and progress of Sentinel, an international collaboration that uses cutting-edge tools for pathogen detection developed at Broad and builds data analysis expertise and digital infrastructure in West Africa. The project connects local clinics and hospitals with scientists at genomics hubs and government health officials, all tracking infections at the local and regional levels.

“Sentinel is more than just a short-lived research program in West Africa,” said Al Ozonoff, the operational director of the US contingent of Sentinel. “This is how we should be conducting surveillance.”

A new viral surveillance system in West Africa is showing the world how to prevent the next pandemic Scientists from the US and West Africa have teamed up to build a better public health network that can quickly detect and respond to emerging viral threats.

We’re thrilled to be a partner of the All of Us Research Program, a National Institutes of Health (NIH) initiative that is changing how health research is done. By partnering with one million people across the United States, the goal of All of Us is to help create one of the largest and most diverse genetic datasets in the world to accelerate research that may improve health. Broad is proud to act as the lead genome center for the All of Us program, generating over half of the genomic data from these biosamples since 2020!

Last week Broad had the pleasure of welcoming NIH Director Monica Bertagnolli and All of Us CEO Josh Denny for a discussion on the All of Us Research Program. Joined by Massachusetts scientists, policymakers, and other leaders, the gathering showcased the impact of equitable healthcare research. https://allofus.nih.gov/news-events/announcements/nih-leaders-met-massachusetts-policymakers-discuss-all-us-research-program

If you are interested in joining the 783,000+ participants nationwide who have already enrolled in the program, visit https://allofus.nih.gov/.

NIH Leaders Met with Massachusetts Policymakers to Discuss the All of Us Research Program | All of Us Research Program | NIH Leaders with the National Institutes of Health met with Massachusetts policymakers last week at the Broad Institute of MIT and Harvard in Cambridge to share key highlights of the work of the All of Us Research Program in building its national health research infrastructure.

PTSD — in which intrusive thoughts, changes in mood, and other symptoms occur after exposure to trauma — can greatly impact a person’s quality of life, but scientists don’t yet understand the neurobiology underlying this condition. Now, researchers have pinpointed 95 parts of the genome that are associated with risk of developing PTSD. The findings could lead to new prevention and treatment strategies.

Scientists uncover 95 regions of the genome linked to PTSD Findings from the largest genetic study of PTSD to date could help explain why only some people develop the condition after experiencing trauma.

Changes in the gut microbiome have been linked to type 2 diabetes, obesity, and inflammatory bowel disease. Now, a new study shows that microbes in the gut could affect cardiovascular disease as well. Broad researchers found that certain species of bacteria consume cholesterol and may help lower cholesterol and heart disease risk in people.

Scientists link certain gut bacteria to lower heart disease risk Study finds several species of cholesterol-metabolizing bacteria in people with lower cholesterol levels.

Meet Alex Navarro, senior program coordinator for the Broad Biomedical Post-baccalaureate Scholars Program. A cell biologist, Navarro helps young researchers envision their own paths to scientific careers, providing support and guidance as they begin their first professional research positions at the Broad and prepare for graduate school in STEM fields. We spoke with Navarro about her path to this unique position and how it informs her work at Broad in this Q&A.

#WhyIScience Q&A: A cell biologist now helps recent college graduates launch their scientific careers Alex Navarro draws from her scientific and personal experiences to guide young researchers toward their professional goals in the Broad’s post-baccalaureate program.

Messenger RNAs (mRNA) are the cornerstone of COVID-19 vaccines and are also being developed as a new class of drugs. To make the molecules better suited as therapeutics, Hongyu Chen, Xiao Wang, and colleagues engineered the mRNA structure, adding multiple “tails” that boosted mRNA activity levels in cells by 5 to 20 times. The multi-tailed mRNAs lasted 2 to 3 times longer in animals compared to unmodified mRNA, and when incorporated into a CRISPR gene-editing system, resulted in more efficient gene editing in mice. The mRNAs could potentially be used as long-lasting treatments that edit genes or replace faulty proteins.

Messenger RNAs with multiple “tails” could lead to more effective therapeutics Scientists have engineered long lasting mRNAs that increased therapeutic protein production in cells and animals.

"My Heart in Your Hands" is finally happening! The panel discussion approaching heart and heartbreak from scientific and arts perspectives take place at 6pm on Thursday, March 28, at Broad Institute of MIT and Harvard, co-presented by Catalyst Conversations. You can attend in person or livestream! I'm on the panel – I'd love to see you there.
More info here: https://www.broadinstitute.org/broad-discovery-series
Or register here: https://broadinstitute.swoogo.com/bdsxcatalyst/begin

Most patients with cancer who are treated with immunotherapies called PD-1 inhibitors don’t respond to the treatments. To better understand why, Broad scientists mapped the genetic activity and location of individual immune cells in lung tumors sampled from 68 people before they were treated with PD-1 inhibitors. They found organized “hubs” of immune cells, and that a subtype of hub called “stem-immunity” hubs was associated with response to PD-1 inhibitors. This hub subtype consisted of specific types of immune cells and signaling molecules known to drive effective anti-tumor responses. The findings could lead to better diagnostics and treatments for lung cancer.

Spatial study of lung cancer reveals immune markers of response to immunotherapy Researchers visualize how immune cells are spatially organized within tumors and show that certain immune “hubs” are linked to better treatment responses.