At UC Santa Cruz, cancer genomics research is yielding new understanding about cancer's inner workings. Cancer genomics tools developed at UC Santa Cruz, including the UCSC Cancer Genomics Browser and UC Santa Cruz Xena provide a complete analysis pipeline from raw DNA reads through the detection and interpretation of mutations and altered gene expression in tumor samples. UCSC biomolecular engineers Joshua Stuart, Nader Pourmand, and David Haussler bring this genomics expertise to collaborations with clinical researchers at medical centers nationally, including members of the Stand Up To Cancer “Dream Teams” and the Cancer Genome Atlas (TCGA), to discover molecular causes of cancer and pioneer a new personalized, genomics-based approach to cancer treatment. UCSC contributes to clinical teams by developing new technology in clinically oriented cancer genomics, including genomic data and electronic medical records.
Institute Faculty in Cancer Genomics
The Treehouse Cancer Initiative, a project of the UC Santa Cruz Genomics Institute, enables sharing of pediatric cancer genomic data. But more than that, it makes it possible to analyze a child's cancer data against both childhood and adult patient cohorts across all types of cancer. This "pan-cancer" analysis of adult and pediatric tumors may identify situations where an adult drug is predicted to work on a subset of pediatric patients.
One approach this project is pursuing explores whether data collected from neuroblastoma patients can be harnessed to identify therapies that will use the patient’s own immune system to fight the cancer. Such approaches have led to lasting remissions in cases of metastatic melanoma and other adult cancers but so far have had limited application in children. The low toxicity of an immunogenomic approach could makes it ideal for treating children.
UCSC informatics–UCSF clinical collaborations
The UC Santa Cruz cancer genomics group teams up with QB3 clinical investigators from UC San Francisco to offer expertise that deepens the value of cancer clinical trials. One such project will result in a centralized pancreatic cancer genome browser (PCGB) that hosts and organizes curated genomic data and offers data visualization and analysis.
The INSTINCT project, a QB3-based multidisciplinary collaboration between UC Santa Cruz and UC San Francisco, applies genomic knowledge to clinical research to address important scientific and health problems in the areas of cancer, autoimmune diseases, and neurological diseases.
Another collaboration between UC Santa Cruz and clinicians at UC San Francisco focuses on the I-SPY 2 breast cancer clinical trial, the first cancer clinical trial to apply whole-genome sequencing across all patients and multiple time points in a trial. A national study, I-SPY 2 aims to identify biomarkers predictive of response to therapy throughout the treatment cycle for women with locally advanced breast cancer. The hope is to gain a deeper understanding of the genetic mutations that give rise to breast cancer and are involved in therapeutic response or resistance.
Big cancer data
The UC Santa Cruz Cancer Genomics Hub (CGHub), a product of the Haussler lab, is a secure repository for storing, cataloging, and accessing cancer genome sequences, alignments, and mutation information from TCGA, a pioneering project involving more than 20 cancer types, the TARGET project, which focuses on the five most severe childhood cancers, and other related projects. The current planned capacity of this data center is five petabytes. We anticipate that the CGHub and will serve as a platform to aggregate other large-scale cancer genomics information, growing to provide the statistical power to attack the complexity of cancer.
Social networking for cancer
Working in the Haussler and Stuart labs, Ted Goldstein is developing a novel cloud-based software application—MedBook—that creates a rapid learning community where scientists, clinicians, and patients collaborate through social media to deliver individualized treatments and better outcomes for cancer patients. This “app” platform matches patients to treatments and clinical trials based on electronic medical record data and the molecular subtypes of their tumors. It learns as it goes, capturing and transforming genomic and outcomes data into new knowledge. Each patient receives treatment based on the best available knowledge from the collective community.
Rapid DNA sequencing
Biomolecular engineer Mark Akeson and biochemist David Deamer are developing new technology for rapid DNA strand sequencing by using protein nanopores—technology that will enable cancer genome sequencing.
Biomolecular engineer David Haussler and research biologist Sofie Salama explore the molecular events that lead to gliomas, a form of brain cancer. They work with a network of collaborators to reveal common mutations and genomic rearrangements associated with gliomas. These genomic features enable identification of patients whose cancer is likely to progress quickly and require the most aggressive treatment versus those who can benefit from a more conservative approach. In parallel their laboratory generates induced pluripotent stem cells (iPSCs) that have genetic lesions common to lower-grade gliomas. These genetically modified iPSCs can be differentiated to neural progenitors—a model of glioma cancer stem cells—to characterize their growth and differentiation properties and test their responsiveness to cancer drugs.