Project Summary/Abstract In the last two decades, genomic sequencing technologies have made remarkable advancements in the quality and number of human genomes sequenced. Moreover, the emergence of long-read sequencing has unveiled a level of genome variation and diversity that is elusive through conventional short-read methods. Cancer is a leading cause of death worldwide, with more than 14 million new cases and 8 million deaths each year. It is often characterized by substantial heterogeneity with respect to the cancer subtype and population group. This heterogeneity manifests at multiple levels, including genetic, epigenetic, and transcriptomic and is fundamental to the understanding of the mechanisms driving cancer phenotypes. Nevertheless, these variations are quite complex and difficult to recapitulate in short-read studies. The goal of my work as the head of the Cold Spring Harbor Laboratory Sequencing Technology and Analysis Shared Resource (STASR) is to provide superior insight and expertise in sequencing technologies and long-read methods in particular. Over the last four years, I have actively engaged in the development of long-read sequencing strategies and collaborated with researchers to harness this powerful tool to meet their scientific goals. I intend to continue to develop and optimize sequencing strategies such as single-cell full length RNA methods, ultra-long (>100kb) DNA sequencing, novel strategies for long read target enrichment, DNA and RNA modification analysis and, to improve general accessibility to genome sequencing technologies. My track record of facilitating genome science at CSHL has proven me to be an essential resource to the scientific mission of the Cold Spring Harbor Laboratory Cancer Center. My ultimate goal is to facilitate collaborative research by directing work across various core facilities, fostering interdisciplinary research, and innovating to address fundamental questions in biology and cancer science. The transformative advancements in genome sequencing technologies, including the breakthrough of long-read sequencing, have shed light on the previously elusive depth of genome variation and diversity. My commitment to developing and optimizing advanced sequencing strategies, coupled with my vision of fostering collaborative research across core facilities, underscores my determination to address fundamental questions in biology and cancer science.