The inaugural class of awardees will receive more than $6 million in funding to accelerate groundbreaking cancer research.
Shannon Stott, PhD
d’Arbeloff MGH Research Scholar 2022-2027
Associate Professor of Medicine
Krantz Family Center for Cancer Research
Explore the Stott Lab
Inaugural Krantz Awards Recipient
2023 Spark Award: Non-invasive blood testing for immunotherapy complications
Shannon Stott, PhD
The Stott laboratory is comprised of bioengineers, biologists and chemists focused on translating technological advances to relevant applications in clinical medicine. Specifically, we are interested in using microfluidics, imaging, and biopreservation technologies to create tools that increase our understanding of cancer biology and of the metastatic process. The Stott laboratory has co-developed innovative microfluidic devices that can isolate extraordinarily rare circulating tumor cells (CTCs) and extracellular vesicles (EVs) from the blood of cancer patients. New microfluidic tools are being developed to both manipulate and interrogate these cells and vesicles at a single particle level. We also look at tumor specimens using multispectral imaging, hoping that the exploration of the spatial relationships between immune cells and tumor tissue will help us better predict treatment response. Ultimately, we hope that by working in close partnership with the clinicians and cell biologists at the Mass General Cancer Center, we can create new tools that directly impact patient care.
Rapid technological advances in microfluidics, imaging and digital gene-expression profiling are converging to present new capabilities for blood, tissue and single-cell analysis. Our laboratory is interested in taking these advances and creating new technologies to help build understanding of the metastatic process.
Our research focus is on:
- the development and application of microfluidic devices and biomaterials for the isolation and characterization of extracellular vesicles
- the enrichment and analysis of CTCs at a single cell level
- novel imaging strategies to characterize tumor tissue, cancer cells, and extracellular vesicles
Extracellular vesicle isolation and characterization
Extracellular vesicles (EVs), such as exosomes, microvesicles, and oncosomes, are small particles that bud off of cancer cells, with some cancer cells releasing up to thousands of EVs per day. Researchers have hypothesized that these EVs shed from tumors transport RNA, DNA and proteins that promote tumor growth, and studies have shown that EVs are present in the blood of most cancer patients. Ongoing work in my lab incorporates microfluidics and novel biomaterials to enrich cell-specific EVs from cancer patients, using as little as 1mL of plasma. Once isolated, we are exploring their protein and nucleic acid content to probe their potential as a less invasive biomarker.
Microfluidics for circulating tumor cell analysis
One of the proposed mechanisms of cancer metastasis is the dissemination of tumor cells from the primary organ into the blood stream. A cellular link between the primary malignant tumor and the peripheral metastases has been established in the form of CTCs in peripheral blood. While extremely rare, these cells provide a potentially accessible source for early detection, characterization and monitoring of cancers that would otherwise require invasive serial biopsies. Working in collaboration with Drs. Mehmet Toner, Shyamala Maheswaran and Daniel Haber, we have designed a high throughput microfluidic device, the CTC-Chip, which allows the isolation and characterization of CTCs from the peripheral blood of cancer patients. Using blood from patients with metastatic and localized cancer, we have demonstrated the ability to isolate, enumerate and molecularly characterize putative CTCs with high sensitivity and specificity. Ongoing projects include translating the technology for early cancer detection, exploring the biophysics of the CTC clusters, and the design of biomaterials for the gentle release of the rare cells from the device surface. We are also developing new strategies for the long term preservation of whole blood such that samples can be shipped around the world for CTC analysis.
High-content and high-throughput imaging of tumor specimens
Tumors can be highly heterogeneous, and their surrounding stroma even more so. Traditionally, the tumor and surrounding cells are dissociated from the tissue matrix for high throughput analysis of each cell. While this allows for important information to be gained, the spatial architecture of the tissue and corresponding interplay between tumor and immune cells can be lost. The Stott lab is developing quantitative, robust analysis for individual cells within the tumor and neighboring tissue using multispectral imaging. We are using this technology alongside downstream imaging processing algorithms to interrogate signaling activity in cancer cells, immune cell infiltration into to the tumor and pEMT in cancer cells. These data will be used to gain an increased understanding in the relationship between pharmacologic measurements and clinical outcomes, ultimately leading to the optimization of patient therapy.
Rabe DC, Ho UK, Choudhury A, Wallace JC, Luciani EG, Lee D, Flynn EA and Stott SL. Aryl-Diazonium Salts Offer a Rapid and Cost-Efficient Method to Functionalize Plastic Microfluidic Devices for Increased Immunoaffinity Capture. Adv. Mater. Technol. 2300210, 2023.
Rabe DC, Walker ND, Rustandy FD, Wallace J, Lee J, Stott SL†, Rosner MR†. Tumor Extracellular Vesicles Regulate Macrophage-Driven Metastasis through CCL5. Cancers. 13(14): 3459, 2021.
Tessier SN, Bookstaver LD, Angpraseuth C, Stannard CJ, Marques B, Ho UK, Muzikansky A, Aldikacti B, Reategui E, Rabe DC, Toner M, Stott SL. Isolation of intact extracellular vesicles from cryopreserved samples. PLoS One. 16(5):e0251290, 2021.
Tessier SN^, Weng L^, Moyo WD, Au SH, Wong KHK, Angpraseuth C., Stoddard AE, Lu C, Nieman LT, Sandlin RD, Uygun K, Stott SL^, Toner M^. Effect of Ice Nucleation and Cryoprotectants during High Subzero-Preservation in Endothelialized Microchannels. ACS Biomater Sci Eng. 4(8):3006-3015, 2019.
Reátegui E*, van der Vos KE*, Lai CP*, Zeinali M, Atai NA, Floyd FP, Khankhel A, Thapar V, Toner M, Hochberg FH, Carter B, Balaj L, Ting DT, Breakefield XO, Stott SL. Engineered Nanointerfaces for Microfluidic Isolation and Molecular Profiling of Tumor-specific Extracellular Vesicles. Nat. Comm. 2018; 9(1).
Shannon Stott, PhDPrincipal Investigator
- Raheel Ahmad, PhD
- Sara Cavallaro, PhD
- Uyen Ho, BA
- Andrew Levy
- Daniel Rabe, PhD
- Daniel Ruiz-Torres, MD*
- Sara Veiga, PhD
- Jillian Wise, PhD**
*Co-mentored with Daniel Faden, MD
**Co-mentored with Michael Lawrence, PhD