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Viktor Adalsteinsson

KI alum Viktor Adalsteinsson develops liquid biopsies to detect cancer

Slice of MIT

Cancer patients who undergo surgery are often left with a frightening question: Did the surgeons get all the cancerous cells? No one wants a recurrence of disease, but additional treatments such as radiation or chemotherapy have significant side effects. That’s why Viktor Adalsteinsson PhD ’15 has been developing tools to support better-informed treatment decisions: so-called “liquid biopsies” that can detect the presence of cancer from a simple blood test.

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A Triple Threat

Upworthy

KI member and Marble Center for Cancer Nanomedicine director Sangeeta Bhatia talks with Upworthy about her uphill climb through the worlds of engineering, medicine, and entrepreneurship, and her continued commitment to pushing boundaries as a scientist and mentor. Bhatia discusses the challenges of increasing the number of women in the STEM pipeline and credits early flexible support with helping her balance the demands the challenges of starting an ambitious research program and a new family.

The Mighty Mighty Ketones

MIT News

Ketone bodies—molecules produced by the breakdown of fat—promote the regeneration of stem cells in the intestinal lining, according to new work from the laboratory of Ömer Yilmaz. In a study appearing in Cell, researchers found that intestinal stem cells produced unusually high levels of ketone bodies, even in the absence of a ketogenic (high-fat) diet, and that these molecules stimulate the Notch pathway to boost stem cell production. Comparisons of diets in mice suggest that ketogenic diets may help repair damage to the intestinal lining, which can occur in cancer patients receiving radiation or chemotherapy. This research was supported in part by the Koch Institute Frontier Research Program through the Kathy and Curt Marble Cancer Research Fund, the MIT Stem Cell Initiative, and The Bridge Project, a collaboration between the Koch Institute and Dana-Farber/Harvard Cancer Center.

Turning the 'Phage on Chemotherapy

Cancer Immunotherapy Research

A subset of white blood cells known as macrophages play a central role in the ridding the body of unwanted cellular threats. However, some microenvironments can render macrophages inactive. Chen Lab researchers, in collaboration with investigators at the University of Southampton, set out to combat bone marrow-resident tumors that are generally resistant to treatment. They demonstrated that low doses of cyclophosphamide chemotherapy activated macrophages when combined with therapeutic antibodies. The combination cleared bone marrow-resident tumor cells, such as B cell lymphoma and breast cancers. The results, published in Cancer Immunotherapy Research, suggest that treating cancer patients with low-dose chemotherapy will not only kill tumor cells directly, but could also aid in immunotherapy via macrophage activation in resistant organs. The immunotherapeutic potential of macrophages was featured in the KI’s 2016 Image Awards exhibition.

In Remembrance: David H. Koch (1940-2019)

MIT Koch Institute

MIT alumnus and MIT Corporation life member emeritus David H. Koch has died at age 79. After receiving the SB (1962) and SM (1963) in chemical engineering at MIT, Koch joined his family’s business, Koch Industries, in 1970. He became president of Koch Engineering in 1979 and served as executive vice president of Koch Industries until he retired for health reasons in 2018.

Koch’s death follows a long battle with prostate cancer, first diagnosed in 1992. Koch has said his experience with the disease encouraged him to become a “passionate crusader” for cancer research. The Koch Institute for Integrative Cancer Research stands as a legacy to that passion. His $100 million gift in 2007 enabled MIT to establish the Koch Institute for Integrative Cancer Research and begin construction of its home in Building 76, where scientists and engineers work together under one roof in pursuit of powerful, new ways to diagnose, treat, and ultimately prevent cancer.

“David’s magnificent gift paved the way for our building, for numerous professorships held by our faculty, and for our unique approach to cancer research,” said Tyler Jacks, director of the Koch Institute and David H. Koch Professor of Biology. “I will always be profoundly grateful for his vision and generosity.

The Condense-ated Version

MIT Koch Institute

Two new studies from the laboratories of KI members Richard Young and Phillip Sharp give a clearer picture of how specialized droplets called condensates may govern the transcription—or conversion—of DNA into RNA. Transcription relies on the coordination of multiple molecules and processes to orchestrate gene activity and regulation. Emerging research into the mechanisms behind these functions point to condensates as a key element in facilitating the necessary interactions.

In a Molecular Cell study, researchers found that weak interactions among disordered regions of transcription factors and other molecules may help determine whether a condensate forms at a stretch of DNA that regulates gene activity. Read more

A Nature study found that separate condensates form for transcription initiation and for splicing and transcriptional elongation, and that the phosphorylation of RNA polymerase II (one component of the transcription machinery) changes a protein’s affinity for one condensate type or the other. Read more.

Young and others have formed a company called Dewpoint Therapeutics to translate condensate biology into potential treatments for a wide variety of diseases, including cancer.

Curiosity: A Tribute to Steven Keating

MIT Koch Institute

With deep admiration for his ready and profound intellectual curiosity, the Koch Institute notes the passing of Steven Keating SM ’12, PhD ’16, from brain cancer at the age of 31. Then a graduate student in mechanical engineering, Keating spoke about his experience with cancer as part of the Koch Institute’s with/in/sight public lecture series in 2014, shortly after surgery to remove a baseball-sized tumor from his brain.

Like many at MIT, he loved data, and he collected a great deal of his own—everything from scans to sequencing information, including 3D computer analyses he used to fabricate models of his own tumor and pilot a technique for faster, cheaper, and better modeling. In fact, it was the IDH mutation revealed by his tumor biopsy that led Keating to the Koch Institute, where Matthew Vander Heiden and Bridge Project collaborators are using 2HG, an ongogenic metabolite produced by mutant IDH, as a biomarker to detect and monitor IDH-mutant cancers. Citing the role knowledge of his previous MRI scans played in his timely diagnosis, Keating became a passionate advocate for patients to have better access to their own health information and for open-sourcing patient data to advance research on cancer and other diseases. 

The Hitchhiker's Guide to Immunotherapy

MIT News

It's no Ford Prefect, but this is one CAR-T that's going places. New research from KI and Marble Center for Cancer Nanomedicine member Darrell Irvine and fellow immune engineer Dane Wittrup, published in Science, takes advantage of the Irvine Lab's hitchhiking vaccine technology to turbo-charge T cells. By stimulating engineered cells' CARs (chimeric antigen receptors) inside the lymph node, the repurposed vaccine was able to activate and expand the population of tumor-killing T cells for a variety of cancer types, including solid tumors for which immunotherapy has previously proven ineffective. The technology has been licensed to biotechnology company Elicio Therapeutics and is expected to begin clinical tests within the next few years. So long and thanks for all the antigens!

Unmasking Mutant Cancer Cells

Clinical Cancer Research

Researchers in the Jacks and White Laboratories have identified a new dosing routine for a well-studied class of anti-cancer drugs that makes tumor cells more easily recognizable to the immune system. The team found that trading traditional bolus dosing for sustained, low-level dosing of heat shock protein (HSP) inhibitors increased the number of mutated protein fragments presented on the surfaces of tumor cells. Their approach, described in Clinical Cancer Research, could improve immunotherapy's effectiveness across more cancer types with fewer side effects and reinvigorate clinical investigations of promising HSP inhibitors. The research was inspired by and builds on work, partly supported by the Koch Institute Frontier Research Program, of late MIT biologist and KI member Susan Lindquist.

Taris Touts Trial Success

MIT Koch Institute

Taris Biomedical, founded by David H. Koch Professor of Engineering Michael Cima and David H. Koch Institue Professor Robert Langer, has made exciting headway in translating its approach to treating muscle-invasive bladder cancer. TAR-200 is an implantable device developed by the Cima and Langer Labs that continuously administers gemcitabine, a chemotherapy drug, for multiple weeks. First, Taris shared positive results from an ongoing study of the device alone, which suggest therapeutic benefit to both patients who undergo radical cystectomy and those unfit for surgical intervention. Two weeks later, the company announced the dosing of the first patient in a new clinical trial, in collaboration with Bristol-Myers Squibb, that combines the device with nivolumab, an approved cancer immunotherapy.

Killing Tumors with Cytokine-ness

MIT News

Immune cell signaling proteins, known as cytokines, are highly toxic—not just to tumors but, unfortunately, to healthy tissue as well. Wittrup Lab researchers are delivering cytokines directly into solid tumors and using the collagen-binding protein lumican to confine these cell-killing proteins within the tumoral space. Their strategy, described in Science Translational Medicine, leverages the protective layer of collagen produced by the cancer cells to prevent leakage of these toxic agents into the bloodstream and opens up previously-closed avenues for combination immunotherapy.