No 67
From Melanocytes to Microfluidics

The Koch Institute's seventh annual Image Awards exhibition opened in the KI Public Galleries on March 24, after much anticipation and hot on the heels of partner Wellcome Image Awards' 20th anniversary exhibition in London. The KI visuals offer glimpses into ten different MIT laboratories and a wide range of topics, from cell signaling, cancer biology, and regeneration, to drug delivery, tissue engineering, and clinical testing. Opening event photos and presentations are accessible via KI social media channels, including Twitter hashtag #KIimages. The new images are also the focus of the latest Cell Picture Show and a popular feature article on STAT. Congratulations to all the winners and thank you to the scientists, artists, and media specialists who served as judges this year, including Catherine Draycott, outgoing Head of Wellcome Images, who has overseen the image exchange program between the KI and Wellcome Trust these past seven years.

Jacks Went Up The Hill

What do you get when you put three leading cancer researchers and a passionate advocate in front of the House Committee on Oversight and Government Reform? Support for cancer research on both sides of the aisle.

On March 29, KI Director Tyler Jacks joined panelists Elizabeth Jaffee (Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University), Mary Beckerle (Huntsman Cancer Institute at the University of Utah), and Tammi Carr (ChadTough Foundation), to testify in front of the bipartisan committee. The panel argued that federal investment in cancer research is critical for the vitality of the nation’s citizens, economy, and status as the global leader in biomedical research. Jacks stressed that the budget cuts currently proposed by President Trump would have “devastating” effects on the nation’s progress against cancer and other diseases — for example, there would be zero new grants funded next year by the NCI — and if enacted, it would suppress an entire generation of cancer researchers and advancements. Following the powerful testimonies and an in-depth Q&A session, the committee expressed their opposition to the proposed cuts and offered another hearing to take a closer look. Read more

Amon Named to American Academy

Congratulations to KI member Angelika Amon, the Kathleen and Curtis Marble Professor in Cancer Research, for being elected to the American Academy of Arts and Sciences. One the nation’s most prestigious honorary societies — Amon was elected to the Academy for her contributions to biological sciences — namely Cellular & Developmental Biology, Microbiology, and Immunology. She will join 17 other current KI faculty members in the ranks of the Academy, which selects “thinkers and doers” from each generation who are leaders that “respond to the challenges facing — and opportunities available to — the nation and the world.” Read more.

AACR Experiences the 'KI Effect'

That the convergence of engineers and scientists can make a difference in cancer research comes as no surprise to our faithful readers. However, 21,000 attendees at the recent American Association for Cancer Research (AACR) Annual Meeting in Washington just experienced the KI effect! Find out more about the groundbreaking plenary sessions featuring KI engineers Angela Belcher and Sangeeta Bhatia, the awards received by KI members, and other exciting happenings at this year’s meeting. Read more.

Not Your Gene-ric Research Result

The road to personalized cancer treatment is long and winding, and often bends toward therapies that target specific gene mutations present in a patient's tumor. However, new evidence from the Amon Lab suggests that there may be more to this paradigm than meets the eye. The researchers found that aneuploidy (the condition in which cells contain an abnormal number of chromosomes) alone can cause significant variability in genetically identical organisms. Their results, published in Cell, could explain why cancers with identical mutations may respond differently to the same treatment. The team hopes this work will inform the development of new treatment strategies to target specific pathways leading to such variabilities among tumor cells. Read more.

Defeating Diagnostic Deficits

A major challenge in fighting cancer is catching it early, when therapies tend to be most effective and patient outcomes most improved. In a recent Nature Biomedical Engineering publication, the Bhatia Lab shows off the capabilities of the new and improved version of their non-invasive urinary diagnostic, which incorporates new design strategies for tumor-specific signal generation and better penetration into tumors.

Current standard clinical detection tools can only reveal tumors about a centimeter in diameter, a size estimated to reflect up to ten years' growth from tumor initiation. The Bhatia group's new nanosensor is even more sensitive than the original: it is >10 times more sensitive and able to detect tumors less than 5 mm in diameter. Moreover, the group is hopeful that the key biomarker used for targeting their nanosensors may prove useful as an indicator for aggressive cancers, in addition to tumor growth, given its role in tumor progression. The Bhatia Lab's original sensors were supported in part by the Koch Institute Frontier Research Program; this latest work was supported in part by the Marble Center for Cancer Nanomedicine and the Ludwig Center for Molecular Oncology. Read more and learn about the more personal story behind this project.

Tethered 'til the End

Langer Lab researchers are coating cancer cells with nanoparticles to make the cells more vulnerable to various drug treatments and, ultimately, cell death. When hundreds of nanoparticles are tethered to a cancer cell, they bat and tug at the tumor cell surface as blood flows by, and compress the veil of molecules around it. Published in Nature Medicinethis one-two punch of physical forces followed by drug delivery makes the cell more susceptible to the cell death signal from the drug. You might even say it puts the cell at the "end of its rope" for resisting treatment. This work was supported in part by the Koch Institute Marble Center for Cancer Nanomedicine. Read more.

Sabatini Wins Lurie Prize

KI member David Sabatini has been named the recipient of the fifth annual Lurie Prize in Biomedical Sciences, which recognizes outstanding achievement by a promising young scientist. Sabatini, whose lab is located at the Whitehead Institute for Biomedical Research, was chosen for his discovery of the mTOR (mechanistic target of rapamycin) cellular pathway as a key regulator of growth and metabolism in response to nutrients, and insights into how mTOR regulation impacts normal and diseased physiology. Sabatini’s research focus has the potential to unlock ways to manipulate the mTOR pathway, perhaps one day protecting against age-related diseases such as cancer by tricking the body into mimicking a fasting state even under nutrient-replete conditions. Read more.

Sending Signals to the Moon

How can specific areas of cancer research contribute to — and gain support from — the National Cancer Institute’s Cancer Moonshot? Science Signaling's podcast team sat down with KI member Michael Yaffe, the publication’s Chief Scientific Editor, to discuss opportunities associated with the federally funded program. Yaffe — whose research focuses on signaling pathways and networks that control cell cycle progression and DNA damage responses in cancer and cancer therapy — described several ways in which these pathways are critical for cancer initiation and progression, and how improved understanding of signaling pathways can be applied to treatment. These advancements align with the Moonshot’s goal to improve the prevention, diagnosis, and treatment of cancer across the nation and the world. Listen now.

Stiff Competition

Members of the Anderson and Langer Labs, in collaboration with researchers at Boston Children’s Hospital, have identified a way to block a signaling molecule that causes fibrosis and effectively prevent the buildup of damaging scar tissue around implanted medical devices. When a device is implanted into the body, cells work to isolate the foreign material and build a defensive wall of dense scar tissue around it, eventually inhibiting its function. In this Nature Materials paper, the researchers identified that the signaling molecule CSF1 plays a key role in this process and showed that blocking the CSF1 cell surface receptor using a small molecule inhibitor prevents the fibrosis from occurring. The ability to stop detrimental fibrosis is key to improving the lifespan of implantable devices — whose capabilities in the areas of detection, monitoring, and drug delivery are critical in mounting effective cancer treatments. The team is now working on ways to deliver CSF1 receptor blocking drugs along with the device itself. Read more.

Programmed for Success

KI researchers Jasdave Chahal and Omar Khan — along with other members of the Anderson and Ploegh Labs — have been developing a more effective way to rapidly generate customized vaccines. Instead of common approaches like using weakened forms of virus, the team uses viral RNA packaged into nanoparticles for delivery to the cells. Once inside the cell, the RNA is translated into proteins that provoke an immune response from the host — with effective results. Last year the team tested therapeutic vaccines for Ebola and influenza; this year they have moved to Zika and, with the help of the Bridge Project, cancer is up next. Read more.

SMARCE Science

The laboratory of KI and Whitehead Institute member Piyush Gupta, the Howard S. (1953) and Linda B. Stern Career Development Professor, has identified a factor, SMARCE1, that drives invasion in early-stage breast cancers. It does so by regulating the expression of proteases, enzymes that degrade basement membrane, an extracellular matrix barrier surrounding all epithelial tissues. The team's findings, published in PNAS, suggest that SMARCE1 could serve as a predictor of whether early-stage tumors will ultimately progress and become invasive. Because more than half of low risk 'in situ' breast lesions are benign and will never become aggressive, these results offer a promising strategy to customize treatment plans, and spare those patients whose tumors are less likely to progress. Read more.

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