Knight Cancer Pilot Project Awardees: Paul Spellman, Ph.D. and Kemal Sonmez, Ph.D.

Paul Spellman, Ph.D., Professor, Molecular & Medical Genetics and Kemal Sonmez, Ph.D., Associate Professor, IDD CSLU

Jointly funded by Knight Cancer Institute Cancer Center Support Grant and OCSSB

Title: "Single Cell Mass Cytometry of Differential Drug Response in Breast Cancer Cell Lines"

Abstract: Breast cancer tumors are heterogeneous, which poses profound challenges for the development of successful therapies as cancer cells within individual tumors may differ greatly functionally and can show a variety of therapeutic responses. The variety often leads to resistance to a certain therapy by selection or cooperation. We propose to study the mechanisms of how subpopulations in human breast cancer cell lines are formed and maintained and how these mechanisms affect their response to therapeutic agents with the goal of informing combinatorial therapies. To this end, we will use single-cell mass spectrometry in the analysis of heterogeneous populations, in order to characterize the differential effects of a set of therapeutic agents on breast cancer cell lines. Measuring over thirty parameters simultaneously in individual cells offers great resolution but at the same time makes the interpretation of data a significant computational and modeling challenge. Existing approaches are limited by their assumptions about how clones generate subpopulations in hierarchies. We propose to develop a modeling framework and a visualization tool that will allow mapping of breast cancer cytometry data onto two dimensions before and after treatment while modeling the mechanism of population changes, which need not adhere to strict hierarchy.

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