Lezon Lab

Computational Systems Pharmacology

Research

Cellular behavior emerges from a complex network of chemical interactions, the details of which remain largely unknown. Developing effective therapies requires a quantitative understanding of these fundamental processes and how they can be safely manipulated to thwart disease. Our lab focuses on constructing mathematical models to assist in diagnosis and treatment of diseases such as cancer and Huntington's Disease.

Drug Repurposing and Combination Therapies

Many complex diseases can only be successfully treated with multi-drug therapeutic strategies. Identifying the proper drugs, doses and scheduling for an effective combination therapy is a daunting task, hindered by the sheer number of permissible combinations. Working with other researchers at the University of Pittsburgh Drug Discovery Institute, the Lezon lab is developing a combined experimental and computational methodology for streamlining the discovery of combination therapeutics. We have applied a novel chemogenomics approach to uncover pathways that modulate cell death in Huntington’s disease, and are creating methodology for predicting which drug targets will generate synergistic effects when co-targeted.

Modeling Cellular Heterogeneity

Non-genetic cellular heterogeneity poses a major obstacle to developing effective personalized therapies. In cancer, for example, slight differences determine whether or not a cell will go on to produce a tumor. The Lezon lab investigates the origins of phenotypic cellular heterogeneity and its potential for improving diagnosis of cancer. The lab is refining methods for automatically quantifying heterogeneity and extracting useful biological information from analysis of cellular phenotype distributions. Working in collaboration with a team at GE, we are developing new computational methods and software to exploit distributions of cellular phenotypes and their spatial organization to assist pathology. We also continue to develop methods for predicting the time-evolution of heterogeneous cell populations.

Contact

We are located in the University of Pittsburgh Drug Discovery Institute:

W956 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
Phone: 412.383.8042
Email: lezon@pitt.edu