Andrew and Erna Viterbi Professor
Professor of Biological and Mechanical Engineering
"Tumors are made up of single cells. In aggregate, we know a great deal about the genetic and cellular defects that cause cancer, but we know comparatively little about the progress of individual cells. Our laboratory develops quantitative and real-time techniques for single cell analysis. We use conventional approaches to fabricate novel fluidic devices, and exploit the unique physical properties associated with micro- and nanoscale dimensions for developing precision measurement methods."
Scott Manalis is the Andrew and Erna Viterbi Professor of Biological Engineering and faculty member in the departments of biological and mechanical engineering at MIT. He received a B.S. in physics from the University of California, Santa Barbara and a Ph.D. in applied physics from Stanford University. Dr. Manalis is a founder of Travera and Affinity Biosensors.
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. Through the MIT Center for Precision Cancer Medicine and a U54 Center Grant from the NCI Cancer Systems Biology Consortium, we are utilizing these platforms within clinical studies in a broad range of tumor types, including leukemias, glioblastoma, colon and pancreatic cancers.
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.
B Hamza, SR Ng, SM Prakadan, FF Delgado, CR Chin, EM King, LF Yang, SM Davidson, KL DeGouveia, N Cermak, AW Navia, PS Winter, T Tammela, CM Li, T Papagiannakopoulos, AJ Gupta, JS Bagnall, SM Knudsen, MG Vander Heiden, SC Wasserman, T Jacks, AK Shalek, SR Manalis. An optofluidic real-time cell sorter for longitudinal CTC studies in mouse models of cancer, PNAS (2019).
NL Calistri, RJ Kimmerling, SW Malinowski, M Touat, MM Stevens, S Olcum, KL Ligon, SR Manalis. Microfluidic active loading of single cells enables analysis of complex clinical specimens, Nature Communications (2018).
RJ Kimmerling, SM Prakadan, AJ Gupta, NL Calistri, MM Stevens, S Olcum, N Cermak, RS Drake, K Pelton, FD Smet, KL Ligon, AK Shalek, SR Manalis. Linking single-cell measurements of mass, growth rate and gene expression, Genome Biology (2018).
MR Luskin, MA Murakami, SR Manalis, DM Weinstock. Targeting minimal residual disease: a path to cure?, Nature Reviews Cancer (2018).
AE Cetin, MM Stevens, NL Calistri, M Fulciniti, S Olcum, RJ Kimmerling, NC Munshi, SR Manalis. Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation, Nature Communications (2017).
MM Stevens, CL Maire, N Chou, M Murakami, D Knoff, Y Kikuchi, RJ Kimmerling, H Liu, S Haidar, NL Calistri, N Cermak, S Olcum, N Cordero, A Idbaih, PY Wen, DM Weinstock, KL Ligon, SR Manalis. Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate, Nature Biotechnology (2016).
N Cermak, S. Olcum, FF Delgado, SC Wasserman, KR Payer, M Murakami, SM Knudsen, RJ Kimmerling, MM Stevens, Y Kikuchi, A Sandikci, M Ogawa, V Agache, F Baléras, DM Weinstock, SR Manalis. High-throughput single-cell growth measurements via serial microfluidic mass sensor arrays, Nature Biotechnology (2016).