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Research at Mass General
Shannon Stott, PhD Assistant Professor of Medicine
The Stott laboratory is comprised of bioengineers and chemists focused on translating technological advances to relevant applications in clinical medicine. Speciﬁcally, we are interested in using microﬂuidics, biomaterials and imaging 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) from the blood of cancer patients. New microﬂuidic technologies are being developed for the isolation of other blood-based biomarkers such as exosomes and microvesicles as well as DNA. Ultimately, we hope that by working in close partnership with the molecular and cell biologists at the Mass General Cancer Center, we can create new tools that directly impact patient care.
Shannon Stott, PhDPrincipal Investigator
*co-directed with Mehmet Toner, PhD
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 1) the development and application of microﬂuidic devices and biomaterials for the isolation and characterization of extracellular vesicles, 2) the enrichment and analysis of CTCs using microﬂuidics, and 3) novel imaging strategies to characterize cancer cells, CTC clusters 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 tumor-specificEVs from the plasma of glioblastoma and pancreatic 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 cancer cells
Cancer cells can be highly heterogeneous, with rare metastasis precursors capable of giving rise to a metastatic lesion mixed in with other tumor cells undergoing apoptosis. Thus, due to this heterogeneity, quantitative, robust analysis for individual cells may be critical for determining a particular cancer cells’ clinical relevance in different disease contexts. Due to limitations in the number of distinct spectra that can be used in wide-ﬁeld ﬂuorescence imaging, high throughput characterization of cells and tissue is traditionally done with three to four colors. Our lab is exploring alternative imaging modalities, such as multi-spectral imaging (MSI), to enable quantitative analysis of multiple (8+) markers on a single cell.
We are interested in using this technology to interrogate signaling activity in CTCs isolated from the blood of cancer patients. 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.
View a list of publications by researchers at the Stott Laboratory.
Au SH, Storey BD, Moore JC, Tang Q, Chen Y-L, Sarioglu AF, Javaid S, Langenau DM, Haber DA, Maheswaran S, Stott SL^, Toner M^, “Clusters of circulating tumor cells traverse capillary-sized vessels” PNAS, 113 (18) 2016. ^co-corresponding
Reátegui E. Aceto N. Lim EJ, Sullivan JP, Jensen AE, Zeinali M, Martel JM, Aranyosi AJ, Li W, Castleberry S, Bardia A, Sequist L.V, Haber D A, Maheswaran S, Hammond PT, Toner M, Stott SL. “Nanostructured coating for immunoaffinity capture and selective release of single viable circulating tumor cells” Advanced Materials 27 (9), 2015.
Li W*, Reátegui E*. Park M-H, Castleberry S. Deng JZ, Hsu B, Mayner S, Jensen AE, Sequist LV, Maheswaran S, Haber DA, Toner M, Stott SL^, Hammond PT ^, “Biodegradable nano-ﬁlms for capture and non-invasive release of circulating tumor cells” Biomaterials 65, 2015.
Miyamoto DT*, Lee RJ*, Stott SL*, Ting DT, Wittner BS, Ulman M, Smas ME, Lord JB, Brannigan BW, Tratuwein J, Bander NH, Wu CL, Sequist LV, Smite MR, Ramaswamy S, Toner M, Maheswaran S, Haber DA, “Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer” Cancer Discovery, Oct23 epub, 2012.
Yu M*, Ting DT*, Stott SL, Wittner BS, Ozsolak F, Paul S, Ciciliano JC, Smas ME, Gilman AJ, Ulman MJ, Contino G, Alagesan B, Brannigan BW, Milos PM, Ryan DP, Sequist LV, Bardeesy N, Ramaswamy R, Toner M, Maheswaran S^, and Haber DA^. RNA sequencing of circulating pancreatic tumour cells implicates Wnt signaling in metastasis. Nature, 487 (7408), 510-513, 2012.
Stott SL*, Hsu C-H*, Tsukrov DI, Yu M, Miyamoto DT, Waltman BA, Rothenberg SM, Shah AM, Smas ME, Korir GK, Floyd Jr. FP, Gilman A, Lord JB, Winokur D, Springer S, Irimia D, Nagrath SN, Sequist LV, Lee RJ, Isselbacher KJ, Maheswaran S, Haber DA, Toner M, Isolation of circulating tumor cells using a microvortex-generating herringbone-chip, Proc Natl Acad Sci. 107 (43): 18392-19397, 2010.
*co-authors, ^Joint corresponding
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