No 84
Taking a Deep Dive with DOLPHIN

DOLPHIN, a non-invasive imaging system from the laboratories of KI faculty members Angela Belcher and Paula Hammond, uses near-infrared light to find tiny tumors no more than a few hundred cells large. In a study appearing in Scientific Reports, researchers used their imaging system to track a 0.1-millimeter fluorescent probe through the digestive tract of a living mouse. The study also showed that DOLPHIN (which stands for "Detection of Optically Luminescent Probes using Hyperspectral and diffuse Imaging in Near-infrared") can detect the probes to a tissue depth of 8 centimeters–about 5 centimeters deeper than any existing biomedical optical imaging technique. The researchers are adapting their imaging technology for early diagnosis of ovarian and other cancers that are currently difficult to detect until late stages. The study was led by Mazumdar-Shaw International Oncology Fellow Neelkanth Bardhan, and was supported by the Koch Institute Frontier Research Program and the Bridge Project

BE the Change You Want to See

KI faculty member Angela Belcher, the James Mason Crafts Professor, will be the next head of MIT's Department of Biological Engineering (BE). Her research spans multiple areas and focuses on harnessing nature’s processes in order to design technologically important materials and devices for medicine, energy, and the environment. When Belcher's appointment begins on July 1, the MIT School of Engineering will have a record high number of women leading departments (four of eight), among them fellow KI faculty member Paula Hammond, head of the Department of Chemical Engineering and David H. Koch Professor of Engineering. Belcher's KI and BE colleague Scott Manalis, the Andrew and Erna Viterbi Professor, will support her as associate department head. Read more.

Tortoises All the Way Down

A new oral insulin delivery capsule could one day replace daily injections for people with type 1 diabetes. Developed by a team led by KI faculty member Robert Langer and longtime collaborator Giovanni Traverso, the capsule, made of stainless steel and biodegradable polymer components, injects a small needle made of compressed insulin into the stomach wall before passing harmlessly through the digestive system. To make sure that the pill lands in the correct orientation to the stomach wall, the researchers developed new device designs that were inspired by the shape of the leopard tortoise, whose angled shell ensures it can roll back on its feet no matter how it falls. In a study published in Science, researchers showed that the capsule could deliver other protein drugs that, like insulin, are too large or delicate to be absorbed undamaged by the digestive system. The team is working with Novo Nordisk to refine the technology and optimize its manufacturing process. Read more.

Spectrum of Opportunity

In an MIT Spectrum profile, KI faculty member Stefani Spranger talks about the advantages and challenges of building a lab at the forefront of cancer immunotherapy research. Like many new labs, Spranger's interdisciplinary team has the opportunity to explore a range of investigative approaches, but hasn't yet had time to build up funding, name recognition, and other resources to support them in their work. That's where an endowed professorship, such as Spranger's appointment last year as the Howard S. (1953) and Linda B. Stern Career Development Professor, can make a big difference. Read more.

Acoustic Cell

Manalis Lab researchers have devised a way to use acoustic waves to measure changes in stiffness as cells go through the cell division cycle over several generations. Appearing in Nature Methods, the technique adapts the laboratory's signature mass-measuring technology and can be used to study biological phenomena such as programmed cell death or metastasis. It could also be combined with mass and growth rate measurements to predict how individual cancer patients will respond to particular drugs. Read more.

Better Mammography through AI

Regina Barzilay's work using AI algorithms for early detection of breast cancer was highlighted in a New York Times feature about technology and health care. With current diagnostic tools, it is difficult to determine if a suspicious lesion seen in a mammogram is high risk, benign or malignant, leading to false positive results that then lead to unnecessary biopsies and surgeries for thousands of women annually. Barzilay's system, now in use at MGH, uses machine learning to detect similarities between a patient’s breast and a database of 70,000 images for which the malignant or benign outcome was known. You can hear Barzilay talk about her work in interviews with WBUR and CNBC

She and her collaborator, physician-scientist Constance Lehman of MGH, will speak in person at the KI on April 30. Barzilay also co-chairs the KI's summer symposium about machine learning and cancer on June 14.

Sizing Up Cells

Why are cells of the same type all the same size? In a study published in Cell, researchers in the laboratory of KI member Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, grew yeast and human cells to several times their normal size and found that the cells' transcription machinery could no longer make enough RNA and protein to support normal function. The team's experiments also uncovered that this process contributes to loss of cell function when cells become senescent. Read more

Vote, STAT!

We're excited to announce that the Koch Institute made it to the second round of the annual STAT Madness competition!

This year, the Love Lab is representing the KI with their biopharmaceutical lab-on-a-bench. You can read more about it at MIT News, read the paper at Nature Biotechnology, or let grad student and co-lead author Laura Crowell tell you all about it.

In the style of NCAA Basketball’s March Madness, STAT Madness is a bracket-style tournament to find the best innovations in science and medicine. We're currently neck-and-neck with Weill Cornell Medicine, so vote now!

Community Highlights

In honor of Women's History Month, the KI is proud to draw readers' attention to WiSDM, the Women in STEM Database at MIT. Founded by four KI researchers and alumnae, this curated, searchable resource is designed to promote visibility of women in MIT's academic community and build a wider, more diverse pool of speakers for conference talks, panels, news stories, and outreach events.

And speaking of talented women....

Meet Julia Ginder, MIT senior, Love Lab researcher, and volunteer for Camp Kesem, which supports children whose parents have cancer. A biology major and public policy minor, Ginder studies the activation signals and cell populations associated with peanut allergies. 

Learn about KI postdoc Ritu Raman's work in responsive biohybrid design. Her winning essay for the Sartorius & Science Prize for Regenerative Medicine & Cell Therapy describes a new model for studying muscle growth, adaptation, and repair using biocompatible engineered and 3D-printed materials. 

All That and a Bag of MicroColonyChips

Measuring the toxic effects that chemical compounds have on cells is critical for developing cancer drugs and in fields like environmental regulation. The current gold-standard cell toxicity test, the colony formation assay, is time-consuming and labor intensive, while quicker tests sacrifice accuracy and sensitivity. The MicroColonyChip retains the sensitivity of the colony formation assay, but is fast and fully automated, delivering data in days rather than weeks. The chip was recently developed by the Engelward laboratory, in part using code developed by KI faculty member Sangeeta Bhatia and former KI postdoc and Mazumdar-Shaw International Oncology Fellow David K. Wood. The technology, described in Cell Reports, could help researchers identify and evaluate new drugs faster, advance personalized medicine applications, and support regulatory use. Leona Samson, KI faculty member emerita, also contributed to the work. Read more.

Pub Crawl: News from the Research Journals

A preclinical study from Bridge Project collaborators Robert Langer and Rakesh Jain explores the relationship between fibrosis and immunotherapy response in metastatic breast cancer. Their results suggest a possible avenue for combination therapy using plerixafor, a drug approved to treat hematologic cancers, and immune checkpoint inhibitors. The work was partly supported by a postdoctoral fellowship from the S. Leslie Misrock (1949) Frontier Research Fund for Cancer Nanotechnology, awarded to co-author and KI postdoc Vikash Chauhan. (PNAS)

The Bhatia Lab is using engineered livers to test the effects of RNAi and other gene therapies. By manipulating metabolic enzyme levels in their model, the team seeks to understand how different patients metabolize drugs and identify possible side effects earlier in the drug development process. (Cell Metabolism)

Anderson Lab researchers announced a new strategy for tracking oxygen levels of implanted cells. Virginia Spanoudaki, scientific director of the Koch Institute Animal Imaging and Preclinical Testing Core Facility in the Robert A. Swanson (1969) Biotechnology Center, is the lead author. The team will apply this technology to the development of implantable islet cells to treat diabetes. (PNAS)

The Hynes Lab examined the interplay between proto-oncogene SRC and the activity of transcriptional coactivators YAP and TAZ, both implicated in tumor formation and metastasis. The work was supported in part by the Koch Institute Frontier Research Program. (Journal of Biological Chemistry)

KI faculty member Amy Keating and colleagues are using a computer program called dTERMen for designing custom peptides to disrupt protein-protein interactions involving Bcl-2 proteins, known to promote cancer growth. (Sequence)

Examining side effects from certain DNA-damaging agents used in chemotherapy, Samson Lab researchers, including 2014 Image Awards winner Aprotim Mazumder, probed the impact of overactive DNA repair mechanisms on photoreceptor cells in the retinas of mice. (Science Signaling)

Researchers in the Yaffe and Lauffenburger labs examined changes in prevalence in reactive oxygen species over the cell cycle. Their results suggest that introduction of mitotic arrest agents could enhance cancer therapy. (Cell Systems)

In Good Company

CRISPR Therapeutics, co-founded by KI faculty member Dan Anderson, reported using the gene-editing technology to treat a patient with beta thalassemia, marking the first clinical trial of a CRISPR/Cas9 therapy by the pharamceutical industry outside of China.

Two KI faculty-founded start-ups were singled out for excellence: Fast Company named Foundation Medicine, co-founded by Eric Lander, the world's most innovative biotech company for 2019, and FierceMedTech named Glympse Bio, co-founded by Sangeeta Bhatia, one of its "Fierce 15."

In other immunotherapy news, Fate Therapeutics, co-founded by KI member Rudolf Jaenisch, reached an important milestone with the FDA's approval of its IND application to begin clinical investigations with the company's off-the-shelf NK cell cancer immunotherapy.

Finally, Moderna announced dosing for the first subject of a Phase 1 clinical trial for the first-ever mRNA-encoded monoclonal antibody to be tested in humans. KI member Robert Langer is among the founders. The company also reported early clinical trial success for their respiratory infection vaccine.

The newsletter of the David H. Koch Institute at MIT: providing up-to-date information on next generation cancer solutions coming from MIT and our collaborators across the world.
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