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Remembering David Baltimore

MIT Koch Institute

With sadness, the Koch Institute marks the passing of Professor David Baltimore. A founding faculty member and formative influence behind the MIT Center for Cancer Research, he was not only a ground-breaking researcher but also a compelling and thoughtful voice for science. 

His discovery of reverse transcriptase changed the prevailing scientific dogma, earned him a 1975 Nobel Prize, and directly enables work in life sciences and biomedical laboratories everywhere. His decades-long advocacy work impacted national policy debates on topics such as recombinant DNA research, the AIDS epidemic, and genome editing.

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Thrown for an R-Loop

Nature Communications

New research from the Yaffe lab appearing in Nature Communications now shows that in highly proliferative tumor cells, Brd4 function is necessary to block collisions on genomic DNA between sites of RNA transcription and DNA replication. They found that cancer cells without BRD4 accumulate R loops, resulting in transcription-replication collisions and DNA damage. The continued replication of cells with R loop-damaged DNA results in increased genome instability and cell death. The findings may help researchers design new combination therapies that take advantage of BRD4’s unique role in blocking DNA damage specifically in oncogenic tumor cells.  

This work was supported in part by the Koch Institute Frontier Research Program, the Koch Institute - Dana-Farber/Harvard Cancer Center Bridge Project, the MIT Center for Precision Cancer Medicine, and a Koch Institute Quinquennial Cancer Research Fellowship.

Fewer Needles, More STING

Science Translational Medicine

A programmable microparticle developed by Langer Lab researchers could make STING-based cancer therapies easier for patients to complete. These immunotherapies (which activate the critical 'stimulator of interferon genes' pathway to boost immune response) produce strong antitumor effects, but must be injected directly into the tumor repeatedly over months, increasing risk for metastasis, chronic injection pain, and infection. The single-injection microparticles release scheduled doses of a STING-based therapy over days and weeks.

In a study appearing in Science Translational Medicine and supported in part by a Ludwig Postdoctoral Fellowship and a Misrock Postdoctoral Fellowship, researchers found the microparticles to be as effective against tumors as multiple injections in mouse models of melanoma and breast cancer, with a reduced chance of metastasis. The study also suggests that the microparticles could deliver STING-based therapies to hard-to-reach tumors.

Michelson Prize for Michael Birnbaum

Human Vaccines Project

Michael Birnbaum received the Michelson Prize for Human Immunology and Vaccine Research 2020 to identify target antigens for HIV vaccine development. His team's novel methodology for studying immune cells' antigen recognition repertoire has multiple applications for other diseases, including cancer and COVID-19, and exemplifies the type of promising early career research supported by the prize.

Shedding Metabolite on Pancreatic Cancer

eLife

Vander Heiden Lab researchers are using a novel nutrient-labeling approach to understand metabolic differences between cell types. A new study published in eLife examines enzyme activity of tumor cells and fibroblasts in organoid cell cultures and mouse models of pancreatic ductal adenocarcinoma, and suggests potential pathways for curtailing tumor growth.

Nanoparticles on Trachea to Greatness

MIT News

Bhatia Lab researchers are breathing new life into their signature protease activity nanosensors. Chemical modifications to synthetic biomarkers (previously used to develop urinary diagnostics for pneumonia and cancer) allow the nanoparticles to release a peptide-based "breath signal" in the presence of respiratory disease. The re-engineered system, described in Nature Nanotechnology, can be used for both diagnosis and monitoring of disease progression or treatment. The researchers are modeling future iterations of the technology on inhalers and breathalyzer tests, and hope to use it to detect specific pathogens such as the SARS-CoV-2 virus.

Standing Up to Pancreatic Cancer

Stand Up to Cancer

Congratulations to Will Freed-Pastor and fellow Lustgarten Laboratory for Pancreatic Cancer Research at MIT researchers on the receipt of a Phillip A. Sharp Innovation in Collaboration Award from Stand Up To Cancer. The Jacks Lab/Dana Farber Cancer Institute team, in conjunction with researchers at Fred Hutchinson Cancer Research Center, will use tumor organoids and engineered T cells to develop novel interventions against pancreatic cancer.

Wittrup Lab Sticks It To Tumors

Cullinan Oncology

The Wittrup Lab's "Velcro vaccine" is the not-so-secret weapon behind Cullinan Oncology's newly launched subsidiary, Cullinan Amber. The company aims to enhance cytokine-based immunotherapy using the lab's collagen-binding technology, which confines these powerful yet toxic treatments to the tumor microenvironment.

There's No Place Like Proteome

MIT Sloan School of Management

A new proteomic analysis platform combining a panel of engineered nanoparticles' protein chemistry and machine learning could open up new avenues to predict, diagnose, and treat disease. In a study appearing in Nature Communications, a team including Robert Langer and other researchers from MIT, Harvard Medical School, Seer and elsewhere, analyzed the proteome in an unbiased, unconstrained manner, and with a depth, breadth, and speed not previously possible. As proof-of-concept, the study demonstrated the platform could be used for the accurate detection of early-stage lung cancer.

Facing Down Mask Shortages

Boston Globe

A team of researchers from Brigham and Women's Hospital and the Koch Institute unveiled their prototype model for a reusable silicone face mask. The design, published in British Medical Journal Open, uses scalable manufacturing technology to produce an easily sterilizable, N95-filter-ready mask for use by health care providers and the general public. Following successful fit and breathability testing in the clinic, the team is working on a second version with improved comfort and durability.

Sizing Up Cell Growth

PNAS

Manalis Lab researchers engineered a larger version of their signature microfluidic mass measurement technology to investigate how cell size and cell cycle contribute to cell growth. The study, published in PNAS, reveals that a cell's growth efficiency is primarily determined by its cell cycle state, not its size, and lays the groundwork for using these devices to monitor growth in large cells and 3D clusters with high resolution. The work was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund and the MIT Center for Cancer Precision Medicine.