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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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The Long History of Rapid Vaccine Development

MIT Koch Institute

In the 1970s, Phillip Sharp and his colleagues on the fifth floor of the MIT Center for Cancer Research set out to unravel the mysteries of tumor virology, cancer genetics, and cell biology. Looking at parts of the adenovirus genome responsible for tumor development, Sharp had long wondered why RNA in the nucleus was longer than RNA found outside the nucleus in the cytoplasm. While this curiosity led to the Nobel Prize-winning discovery of split genes and spliced RNA, neither Sharp nor his colleagues were thinking about the possibility of mRNA vaccines at the time. Nevertheless, that discovery, together with many years of mRNA research and key technology advances like nanoparticle delivery of RNA, set the stage for companies such as Pfizer and Moderna to develop mRNA-based COVID-19 vaccines with record speed.

The discoveries that enabled RNA vaccines | RNA vaccines explained

Live and Let Liver

MIT News

The Cima Lab has developed a non-invasive diagnostic tool to assess liver damage. The technology, described in Nature Biomedical Engineering, uses nuclear magnetic resonance to measure fat content and detect scarring that can be indicative of fatty liver disease and a precursor to fibrosis, both known risk factors for cancer.

Barzilay Argues for Equity in AI-Influenced Health Care

Stat News

Machine learning pioneer Regina Barzilay is holding AI developers to a higher standard, flagging commonly-used machine learning models as likely perpetrators of health care inequities. Barzilay cites her experience image-based breast cancer risk prediction, where existing AI models assessed white women’s risks more accurately than for women of African and Asian descent. (subscription required)

Conducting Research in a New Way

MIT News

A new imaging technique from the Boyden Lab, published in Cell, identifies up to five different molecule types from random, distinct locations throughout a cell, uncovering a full “symphony” of cellular activity. The technology will be instrumental in understanding how cell signaling differs between cells from healthy and diseased tissue. 

Small Molecule, Big Potential

MIT News

A multidisciplinary team from the Koehler Lab identified a compound that could target key proteins in advanced prostate cancer, as well as a variety of other cancer types. The compound, KI-ARv-03, works by selectively binding to an androgen receptor cofactor known as CDK9, thereby destabilizing androgen receptor proteins in a key pathway contributing to the development of castration-resistant prostate cancer (CRPC) and curbing the expression of associated oncogenes. The study appears in Cell Chemical Biology and was supported in part by the Koch Institute-Dana-Farber/Harvard Cancer Center Bridge Project, the MIT Center for Precision Cancer Medicine, and Janssen Pharmaceuticals, Inc., via the Transcend partnership.

Kronos Bio, co-founded by Koehler, has developed a more powerful version of the CDK9 inhibitor, KB-0742 and recently received IND clearance to begin a Phase 1/2 clinical trial in 2021. Preclinical tests in cell lines and mouse models revealed significantly reduced tumor growth in CRPC models and other oncogene-addicted cancers.

Age of Senescence

MIT Biology

The Hemann and Walker labs previously discovered that the compound JH-RE-06 enhanced the tumor-shrinking effects of DNA-damaging chemotherapies. While they expected JH-RE-06 to amplify programmed cell death induced by DNA damage, two studies appearing in PNAS showed that JH-RE-06, or genetically ablating the pathway targeted by JH-RE-06, instead puts tumor cells in a permanently dormant state known as senescence. Because senescent cells are often cleared by immune cells, these findings suggest a complementary approach to traditional chemotherapies. 

Growing Evidence

bioRxiv

In a biorxiv paper posted two days before Amon’s passing, researchers in her group, with collaborators in the Lees and Yilmaz labs, illuminate the relationship between stem cell size and function, and tissue aging. Despite great variability in cell size and shape between tissues, stem cells are invariably small. The Amon lab’s studies present evidence that small size is critical for hematopoietic stem cell function. Analyses of these cells also showed that they get progressively bigger with organismal aging, and that the larger stem cells are less functional. These findings suggest that large size causes stem cell function to decline during aging. This work was partly supported by the MIT Stem Cell Initiative.

Freeze Frame

Structure

The KI’s Robert A. Swanson (1969) Biotechnology Center regularly adapts and evolves specialized techniques and technologies. In a cover-winning Structure paper, researchers from the Peterson (1957) Nanotechnology Materials Core Facility have developed a new 3D imaging workflow that integrates three imaging approaches to visualize the same sample at cryogenic temperature at different scales, providing a unique view into features of cell structure. Demonstrated in yeast, the process could be used for large-scale studies of frozen specimens in healthy, diseased, and therapeutic conditions. Currently, the research team is the only one in the US with the specific technological capabilities—volume cryo-focused ion beam scanning electron microscopy, cryo-fluorescence confocal microscopy, and transmission cryo-electron tomography—to run this entire workflow.

Vaccine Around Town

Spectrum

Spectrum showcases two cancer- and pandemic-relevant research projects in their COVID-19-themed fall issue. Love Lab researchers are optimizing their rapid vaccine development platform to accelerate the advancement and production of COVID-19 vaccine candidates. The Chen Lab is exploring vaccine enhancement agents to improve immune response and decrease inflammation.

Positive Signals

PR Newswire

Results were recently announced from a Phase 2 trial, launched with support from the Bridge Project, to test a synergistic drug combination identified in the Yaffe lab. Patients with metastatic castration-resistant prostate cancer were assigned one of three different dosing schedules; the majority saw improved or stable disease in all three groups. Additionally, the team has identified a biomarker associated with therapeutic response.