Area of Interest
Weissman’s research focuses upon the role of aberrant chromatin remodeling in cancer development. Specifically, his laboratory has concentrated upon loss of activity of the SWI/SNF chromatin remodeling complex in the development of non-small cell lung carcinoma, a cancer strongly associated with environment pollution, small particle exposure and smoking. His group has also studied the role of SWI/SNF complex mutations in the development of two rare cancers, malignant rhabdoid tumor and small cell carcinoma of the ovary, hypercalcemic type. Previous studies from Weissman’s laboratory have shown that inactivation of individual components of the complex alter gene expression through changes in chromatin organization and through altered RB, TP53 and AKT signaling. Furthermore, the loss of SWI/SNF complex may induce epigenetic instability in cancer cells leading to gene silencing via a mechanism independent of DNA methylation. We are currently dissecting how changes in the chromatin landscape contribute to the onset of these cancers. In addition, the laboratory has recently expanded studies into the role of oxidative stress in the development of human squamous cell carcinomas. Activating mutations of the NFE2L2 (NRF2) transcription factor occur frequently in these cancers leading to enhanced resistance to oxidative stress. In collaboration with Dr. Ben Major’s laboratory, we have found an esophageal hyperplastic phenotype in our novel genetically engineered mouse model (LSL-Nrf2E79Q). While we continue our efforts to model the role of NRF2 activation in the development of human lung squamous cell carcinomas, we are also expanding these efforts into the etiology of esophageal squamous cell carcinomas.
Awards and Honors
- 2016 Received the Journal of Pathology Jeremy Jass Prize for Research Excellence in Pathology
- 2002 Recipient, Joe Grisham Award for Excellence in Graduate Student Teaching, Department of Pathology and Laboratory Medicine, UNC-Chapel Hill
- 1986 Recipient, Procter and Gamble University Exploratory Research Program Grant