Research

Other Projects and Collaborations

Identifying and Targeting Lung Cancer Stem Cells (CSCs)

We have identified a subpopulation of lung cancer cells within tumors (~0.1 to 30 percent of the cells) that have characteristics of stem cells with dramatically enhanced tumorigenic properties compared to the remainder of the tumor cell population. We are working to identify markers of these cells and also therapeutic targets.

Currently a very important marker is aldehyde dehydrogenase; lung CSCs express one or the other of these isozymes (ALDH1A3 and ALDH1A1). By targeting these enzymes we can achieve dramatic therapeutic efficacy in lung cancer preclinical models.

As part of this we have identified pSTAT3 and EZH2 as new lung CSC therapeutic targets. This project is done in collaboration with the laboratory of Hamon Center faculty member James Kim, M.D., Ph.D., which has genetically engineered mouse models of lung cancer stem cells.

Developing ASCL1 Targeted Therapy for Small Cell Lung Cancer and other Neuroendocrine Lung Cancers

In collaboration with the labs of Jane Johnson, Ph.D., (Department of Neurosciences) and Melanie Cobb, Ph.D., (Department of Pharmacology) we have identified ASLC1 as a major lineage oncogene for the important subgroup of lung cancers with neuroendocrine features.

As part of this we have ChipSeq data indicating all of the downstream targets for ASCL1, many of which are druggable, as well as totally novel upstream regulation of ASCL1 expression by the MAPK pathway.