Srinivas Ramachandran, PhD

Categories

Epigenomics, cfDNA, chromatin dynamics, diagnostics

Specialty

Lung Cancer treatment response, ER+ breast cancer characterization 

Location

University of Colorado Anschutz Medical Campus, RC1 South

Project Objective

Develop methods that utilize plasma cfDNA for genomic characterization of tumor biology

Project Description

Distinct and dynamic genomic packaging underly growth, development, differentiation, and disease states including tumor initiation. Our long-term goal is to understand how distinctive genomic packaging that reflects cellular identity is established and maintained. We want to uncover mechanisms that sculpt genomic accessibility by developing novel computational and experimental genomic methods that map chromatin structure at high temporal and spatial resolution. This line of research combines quantitative and structural biology with genomics and chromatin biochemistry. We have generated structural insights from epigenomic datasets, an effort we term “structural epigenomics”. Using this approach, we have identified nucleosomal intermediates formed during transcription and chromatin remodeling in vivo and have also identified the tissue of origin of human cell-free DNA. Mapping the chromatin structure of cell-free DNA (cfDNA) enables us to surveil disease states in a minimally invasive manner. Using chromatin structural information in cfDNA to build the comprehensive regulatory landscape of tissues giving rise to cfDNA can lead to cancer diagnostics that are more sensitive than current methods.