The Riethman laboratory focuses on the detailed characterization of genetic and epigenetic features of human subtelomeric and telomeric DNA as they relate to cancer and aging. This work is currently in two main areas.
In the first, novel experimental and computational next-gen sequencing based approaches are being developed and used for analysis of subtelomeric structural variation, mutation, and annotation of human subtelomeric DNA. The Riethman laboratory, in collaboration with the Lieberman and Davuluri labs, has used existing next-gen datasets to annotate our updated human subtelomere sequence assemblies as part of an effort to understand the role of subtelomeric chromatin in the transcriptional regulation and function of a long noncoding RNA (TERRA) essential for telomere integrity (Deng et al., 2012). We have recently extended and refined our computational pipeline to enable efficient mapping of next-gen datasets to extended subtelomere DNA regions, where critically important genes are located and where previous analyses have been hampered by subtelomeric segmental duplication content. In the second area, the relationship of telomere length dynamics with telomere function and dysfunction is being investigated in several distinct contexts:
1. Measuring telomere length as an environmentally-impacted biomarker associated with prostate cancer incidence and progression (collaboratively with Dr. T. Rebbeck and colleagues at University of Pennsylvania);
2. Developing both next-gen sequence-based and single-molecule fluorescence-based approaches to detect and characterize mutated and dysfunctional telomeres in cancer cells as well as in cells of individuals bearing constitutional ring chromosomes (collaboratively with Dr. Ming Xiao at Drexel and Dr. Nancy Spinner at CHOP); and
3. Developing a novel method for the purification and nanomap-assisted sequencing of subtelomeric DNA from any genomic source, for the characterization of new subtelomeric structural variants and mutations (in collaboration with Dr. Ming Xiao, Drexel).
These annotations include subtelomere duplicon content and organization as well as gene models and subtelomere sequence features. Annotation tracks of enrichment profiles and peaks from next-gen dataset read mappings and analyses as described in Deng et al. (2012), but extended across all 500 kb-sized subtelomere assemblies, are included. Additional annotation tracks derived from next-gen datasets are being added as their subtelomere mapping and analyses are completed.