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Manalis Laboratory - MIT Departments of Biological and Mechanical Engineering

 

We develop microfluidic technologies to measure biophysical properties of single cells (e.g. mass, growth, deformability) and we apply these technologies to problems in cancer, immunology, and microbial research.  Our research projects generally fall within the following areas:

Functional assays for precision medicine in cancer
Despite tremendous advances in our understanding of cancer pathogenesis, the treatment of individual patients with either conventional chemotherapy or targeted agents remains highly empiric.  Better information about which treatment to offer an individual patient could improve efficacy while sparing patients from the toxicity of therapies that offer no benefit. To address this need, we are developing new technology platforms for predicting therapeutic response in which biophysical properties of individual tumor cells are measured in response to ex vivo treatment of combination therapies.  Together with collaborators at the Dana Farber Cancer Institute, we are utilizing these platforms within clinical studies in a broad range of tumor types, including leukemias, glioblastoma, colon and pancreatic cancers.

Linking biophysical to genomic properties in single cells
We are pursuing several directions where high precision measurement of single cell biophysical properties reveals interesting subpopulations.   Examples include activated immune cells with divergent growth kinetics, bacteria responses to antibiotics or antimicrobial peptides and tumor cell response to targeted therapies.  In collaboration with the Shalek Lab (MIT Chemistry), we are linking biophysical properties to gene expression (sc-RNA-Seq) at the single-cell level and at scale in order to understand the mechanisms that govern growth heterogeneity in these examples.

Real-time monitoring of circulating tumor cells in genetically engineered mouse models
Despite the central importance of circulating tumor cells (CTCs), understanding of their role in metastasis has been limited by the extreme difficulty of characterizing CTC populations over time and linking them to metastases that occur during natural tumor progression. Genetically engineered mouse models (GEMMs) have emerged as an attractive model for recapitulating the natural multistage evolution of cancers as they now allow for inducible, tissue-specific expression of oncogenes as well as conditional, tissue-specific deletion of tumor suppressors. In collaboration with the Jacks lab (MIT Biology), we are using GEMMs together with microfluidic technology to understand how progression to metastasis correlates with, and could be explained by, the circulatory dynamics and physical properties of CTCs. Our approach will make possible a series of experiments that can answer fundamental questions about the relationship between CTC characteristics and metastasis and will ultimately potentiate hypothesis-driven tumor biology studies and large-scale preclinical exploration of therapeutic strategies that are not feasible in patients.