Cellular and Biomolecular Engineering
Office: BME 4.202F
- Cancer systems biology
- Heterogeneity and cell state plasticity
- Gene regulatory networks
- Chemotherapy drug resistance
- Normal differentiation and differentiation therapy
Our lab is interested in understanding cancer as a complex biological system.
To gain novel insights into the disease, we apply a systems approach that does not treat one particular pathway as causation but instead looks upon the ensemble of pathways (the gene regulatory network) as the determinant of cell state. By integrating approaches from dynamic systems, computational sciences, microfabrication and molecular cell biology we seek to tackle fundamental questions of tumor cell-state alterations and response to treatment.
Cancer is caused by dysregulation of normal gene expression programs. The technology to characterize the molecular changes in a particular patient’s tumor is increasingly available in the clinic and this type of analysis has been useful in classifying subtypes of tumors. However, in addition to inter-tumor heterogeneity there exists substantial intra-tumor heterogeneity. Subpopulations of cells within a single tumor vary widely in terms of gene and protein expression, metastatic potential and sensitivity to particular drug treatments.
To effectively treat the “moving target” that is an evolving tumor cell population, we seek to develop models that aid in identifying, monitoring and predicting changes in heterogeneity. We study the dynamics and variation of biological responses to defined perturbations in order to develop rationale, personalized therapies. This problem is examined at multiple spatial scales to uncover the relationship between cell-cell heterogeneity and the population-level response to drug treatment.
Little is known about how biological systems exploit or suppress heterogeneities. Thus this is a fundamental design principle that may be broadly applicable to many cancers and indeed other diseases as well, since regardless of drug targeting and specificity there typically remains a non-responder disease cell population due to intrinsic variation.