THE UC SANTA CRUZ GENOMICS INSTITUTE. David Haussler Distinguished Professor, Biomolecular Engineering Scientific Director
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1 THE UC SANTA CRUZ GENOMICS INSTITUTE David Haussler Distinguished Professor, Biomolecular Engineering Scientific Director April 8, 2015
2 OUR MISSION Unlocking the world s genomic data to accelerate medical and scientific breakthroughs
3 SPECIES CONSERVATION Understanding extinction Restoring ancient diversity Lessons for human health Stewardship of our planet
4 DECODING HUMAN HEALTH Adult and childhood cancer Autoimmune disease Congenital abnormalities Infectious disease
5 WHAT S POSSIBLE Defeat cancer through the global exchange of genome information
6 DATA HELD IN SILOS, UNSHARED No one institute has enough on its own to make progress
7 NEW PLATFORM ALLOWS SHARING We are building infrastructure for the next great leap in genomics G
8 ALLIANCE FOR DATA SHARING
9 THE UCSC GENOME BROWSER Unmatched global resource used by 130,000 researchers 1.2 million page hits per day
10 HUMAN GENOME VARIATION MAP Replacing the current linear reference genome with a graphical format to truly capture human diversity Team: David Haussler, Benedict Paten, Darrell Long
11 MOMENTUM ON THE PLATFORM Scaling up with new funding in 2015, including NIH Center for Big Data in Translational Genomics $11 million over 4 years Cancer genomics cloud pilot contract (Broad) ~$780,000 over 2 years CIRM Center of Excellence for Stem Cell Genomics $4 million over 5 years Integrative pathway analysis to predict biomedical outcomes $3.5 million over 5 years Human Genome Variation Map (Simons) $1 million for 1 year
12
13 CANCER IN CHILDREN 42 children are diagnosed with cancer every day in the US Average age of diagnosis: 6 years 1 out of 300 will get cancer before turning 20 Bone and soft tissue, 11% Others, 20% Neuroblastoma, 8% Lymphoma, 11% Leukemia, 31% Brain, 19%
14 CHILDHOOD CANCER TREATMENT 5-year survival rate in children: 80% 1-3 years of treatment includes all these modalities: Combinational chemotherapy Surgery Bone marrow transplant Radiation Biological therapy Immunotherapy Most targeted treatment agents for childhood cancers come from trial-and-error of adult drugs National Cancer Institute
15 LONG-TERM OUTCOMES Disappointing in childhood cancer cases 22% Live no chronic conditions 34% Die 30-year follow-up since diagnosis 25% Survive mild moderate chronic conditions 19% Survive life-threatening conditions People against childhood cancer (PAC2)
16 A NEW APPROACH Can we use the vast amount of research into common adult cancers to identify new treatments for rare childhood tumors?
17 TREEHOUSE CHILDHOOD CANCER PROJECT A UC Santa Cruz big data bioinformatics initiative
18 PATIENT 79: EIGHT YEARS OLD Diagnosed with dural-based sarcoma Treated with aggressive chemotherapy, autologous stem cell transplant, and local radiation Two years later metastases to lungs No standard treatment options, so Patient 79 enrolled in a personalized genomics clinical trial Tumor genome sequencing revealed an EWSR1-ATF1 gene fusion, which has no obvious molecular targets Can comparison with other adult and pediatric cancers help? National Cancer Institute
19 PAN-CANCER ANALYSIS Tumor map of adult cancer types AML Breast Ovarian Tumors arranged by genomic similarity Generally yields grouping by diagnosis Head and neck Bladder Lung squamous Colon Rectal Lung adeno Uterine Kidney Glioblastoma
20 INSIGHTS FROM THE EXCEPTIONS Tumors arranged by genomic similarity Exceptions to the groupings suggest new treatments adult sarcoma adult uterine carcinosarcoma pediatric neuroblastoma Lower-grade glioma patient 79 (pediatric sarcoma) Glioblastoma uterine corpus endometrial carcinoma adult lymphoma
21 APPLYING AN ADULT TREATMENT Some pediatric neuroblastomas are driven by the ALK pathway and respond to treatment with ALK inhibitor crizotinib a treatment approved for adult lung cancer Phase I clinical trial at Children s Hospital of Philadelphia: Of 27 neuroblastoma patients, 2 achieved complete remission Edie, one of the two patients whose tumors disappeared completely on crizotinib
22 ALK expression level ALK EXPRESSION LEVELS Comparison shows Patient 79 s sarcoma is like the ALK-driven neuroblastomas that responded to crizotinib Other neuroblastoma ALK-driven neuroblastoma (responds to crizotinib) Other Patient 79 (sarcoma)
23 CAN CRIZOTINIB HELP PATIENT 79? Started on Crizotinib a few weeks back based on your information. Patient is due for a repeat CT chest in the next week or two. Will let you know what it shows. fingers crossed it will be improved. Treating Oncologist, April 6, 2015
24 IMMUNOGENOMICS Harnessing a patient s own immune system to fight cancer Integrating the complexity of an individual s tumor and immune response to identify treatments that will work Team: David Haussler, Sofie Salama
25 TREEHOUSE PROJECT OVERVIEW Pediatric cancer platform that enables comparisons to adult cancers Cohorts, data repositories Information that does not require protection Protected genomic info Treehouse components Access Collaborations External data source Precision medicine trials Individual laboratories Treehouse open tier UCSC Xena Browser open/embargoed Analysis container TumorMap Xena PrecisionImmuno Results reviewed by disease experts Hospital/la boratory Data processing container Treehouse protected tier Data processing container CGHub, NCI GDC Translational and clinical leads Team: David Haussler, Josh Stuart, Sofie Salama, Olena Morozova Logo by Julie Himes
26 TREEHOUSE COLLABORATORS Expertise spanning childhood cancers 1. Phoenix Children s Hospital 2. Children s Hospital of Los Angeles 3. Children s Hospital of Orange County 4. Children s Hospital of Philadelphia 5. Hospital for Sick Children 6. British Columbia Children s Hospital 7. British Columbia Cancer Agency 8. Seattle Children s Hospital 9. Texas Children s Hospital 10.University of Chicago Genomic Data Commons 11.University of California Santa Cruz 12.Baylor College of Medicine 13.Fred Hutchinson Cancer Research Center 14.The Genome Institute at Washington University 15.Stanford School of Medicine 16.National Cancer Institute 17.SAGE Bionetworks 18.Perelman School of Medicine, U Penn Kids v. Cancer Unravel Pediatric Cancer Team Finn Foundation
27 NOW WHAT? With just a few cases, we are lucky to find similarities that will help individual children With a million tumors in our network, it will no longer require luck Private support can make the difference
28 genomics.ucsc.edu THANK YOU!
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