Specific Aim 2. We will explore the genomic instability and genetic complexity of cancer
Genomic instability is a hallmark of cancer and drives chromosomal rearrangements that lead to oncogene activation and tumor suppressor deactivation. JAXCC members have developed advanced technological platforms and computational methods for characterizing the genomes of patient samples and model systems developed in Aim 1. The knowledge generated from these characterizations is integrated with functional studies to delineate the mechanisms that drive genome restructuring. The results of this work, in turn, are used to identify specific regulatory and protein outputs that reprogram the cancer cell. In ongoing and future work, we will apply our model systems and genome technologies to:
Study maintenance of genomic stability, DNA damage response and telomere maintenance mechanisms; Work in this area includes functional studies of genes involved in maintaining chromosomal and genomic integrity during germ cell development and meiosis as well as in cancer cells.
JAXCC members working in this area include: Ewelina Bolcun-Filas, Robert Braun, Greg Carter, Mary Ann Handel, Charles Lee, Petko Petkov, Laura Reinholdt, Roel Verhaak, and Christine Beck.
Determine structural and functional mechanisms mediating epigenomic dynamics; This work reaches from the functional effects of the local chromatin state to the mechanisms regulating the three-dimensional topology of the genome and its impact on coordinated gene expression. Research aims to reveal higher-order regulatory mechanisms of tumorigenesis.
JAXCC members working in this area include: Jacques Banchereau, Albert Cheng, Sheng Li, Krishna Karuturi, Yijun Ruan, Jen Trowbridge, Duygu Ucar, and Roel Verhaak.
Discover genomic mechanisms of resistance to targeted, standard and DNA repair pathway
chemotherapies as well as immunotherapies; This work brings together discovery of structural variants and the mechanisms that generate them with investigations into tumor heterogeneity, progression, evolution, and therapy response.
JAXCC members working in this area include: Olga Anczukow, Judith Blake, Carol Bult, Elissa Chesler, Jeff Chuang, Krishna Karuturi, Shengdong Ke, Ching Lau, Charles Lee, Ed Liu, Karolina Palucka, Paul Robson, Yijun Ruan, Lenny Shultz, Jen Trowbridge, Duygu Ucar, Roel Verhaak, Julie Wells, and Chia-Lin Wei.