Leveraging multi-omics approaches to study determinants of lineage plasticity in cancer 

Under chronic stress or therapeutic pressure, cells undergo epigenetic reprogramming away from defined lineage states towards more primitive states with enhanced pluripotent potential. Identifying mechanisms that drive this lineage plasticity is vital in understanding how tumors develop and evade therapeutic response. 

Using omics scale data to investigate and quantify plasticity 

Integrative analysis (RNA-seq, ATAC-seq) of preclinical models and publicly available bulk and single-cell human tumor data has revealed roles of MUC1 in driving stemness and intracellular interferon signaling in various tumor types, including castration-resistant prostate cancer (Figure 1) and non-small cell lung cancer. 

Figure from a scientific research study
Figure 1: In collaboration with Donald Kufe (DF/HCC), we have identified MUC1 as a driver of stemness and intratumoral interferon signaling in multiple cancer types, including castration-resistant prostate cancer. Hagiwara M, et. al., Oncoimmunology, 2022. Click for larger image

Experimental and computational analysis determined a role of NCOR2 in suppressing response to androgen deprivation therapy in prostate cancer models. Integrative multi-omics revealed interactions of NCOR2 with pioneering transcription factors that had important roles in governing global transcription, DNA methylation and super-enhancer function. 

Further, we leveraged whole-genome bisulfite sequencing to identify regions of dynamic methylation in the normal prostate epithelial differentiation program, which we subsequently revealed were aberrantly methylated in prostate cancer. 

Connect with the Long Lab 

Email: Mark.Long@RoswellPark.org  
Phone: 716-845-2541 

Department of Biostatistics and Bioinformatics 
Roswell Park Comprehensive Cancer Center 
Elm and Carlton Streets 
Buffalo, NY 14263