Genomics, Advanced Technology, and the Future of Medicine Francis S. Collins, M.D., Ph.D. Director, U.S. National Institutes of Health FAPESP 22 May
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1 Genomics, Advanced Technology, and the Future of Medicine Francis S. Collins, M.D., Ph.D. Director, U.S. National Institutes of Health FAPESP 22 May 2014
2 NIH: Steward of Medical and Behavioral Research Science in pursuit of fundamental knowledge about the nature and behavior of living systems... and the application of that knowledge to extend healthy life and reduce illness and disability.
3 NIH Funds Scientists Across U.S. Alaska Hawaii
4 and around the globe Brazil is our most significant South American partner Source: Foreign Tracking System
5 Major Opportunities for Biomedical Research Apply breakthrough knowledge and technologies to enhance understanding of biology and disease Translate basic science into better treatments Improve health care through science Sharpen focus on global health Reinvigorate the biomedical research community
6 Major Opportunities for Biomedical Research Apply breakthrough knowledge and technologies to enhance understanding of biology and disease Translate basic science into better treatments Improve health care through science Sharpen focus on global health Reinvigorate the biomedical research community
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10 Variant A Variant B
11 Genetic Variants Associated with Disease Risk
12 S-01 J-02 M-02 S-02 J-03 M-03 S-03 J-04 M-04 S-04 J-05 M-05 S-05 J-06 M-06 S-06 J-07 M-07 S-07 J-08 M-08 S-08 J-09 M-09 S-09 J-10 M-10 S-10 J-11 M-11 S-11 J-12 M-12 S-12 J-13 M-13 S-13 J-14 Cost of Sequencing a Human Genome September 2001 January 2014 $ $ $ $ $ $1.000
13 The Cancer Genome Atlas Coordinated effort to accelerate understanding of cancer through genome analysis to improve diagnosis, treatment, and prevention Provides analysis of > 20 types of cancer, including Leukemia Brain Breast Lung Colon Ovary Uterus Bladder
14 The Cancer Genome Atlas: Comparing Fingerprints of Cancer Types Searching for shared genomic fingerprints 12 cancer types Tumor samples from 3,300 patients Found 127 significantly mutated genes shared by subsets of samples across cancer types Potential significance for Precision medicine customizing treatment for individual patients Therapeutic development identifying key cellular pathways to find likely drug targets
15 International Cancer Genome Consortium ICGC: global effort to Catalogue genomic abnormalities in tumors from 50 different cancer types and/or subtypes Make data available to entire research community
16 International Cancer Genome Consortium 71 projects in 17 jurisdictions
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18 Exposure Clinical Myriad Data Types Genomic Other Omic Imaging Phenotypic
19 Disorders with Known Molecular Basis Source: Online Mendelian Inheritance in Man, Morbid Anatomy of the Human Genome
20 Undiagnosed Diseases and NIH Undiagnosed Diseases Program (UDP) Patients with longstanding, undiagnosed medical conditions are seen at NIH Clinical Center UDP s NIH-wide staff, led by Dr. William Gahl, has: Evaluated ~3,000 medical records Accepted ~700 cases Determined some diagnosis in ~25% Next: National Undiagnosed Diseases Network Will expand program s data, approaches throughout the country
21 Identifying Causes of Rare Diseases: DADA2 Mystery: what was causing recurring fevers, rashes and strokes in 3 young patients seen at NIH Clinical Center? Detectives from across NIH s Intramural Program investigated Molecular insight: whole exome sequencing revealed 2 mutated copies of gene that codes for ADA2 Enzyme key for blood vessel development; immune cell balance ADA2 deficiency vascular, immune abnormalities inflammation fevers, rashes and strokes Dubbed this rare condition, DADA2 Implications: For patients with DADA2, promise of better treatment For the many adults who suffer a stroke, promise of new insights into causes prevention treatment
22 Understanding the Brain Capturing the Imagination Learning the Language of the Brain
23 Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative: NIH goals Generate a Census of Cell Types Create Structural Maps of the Brain Develop New Large-Scale Network Recording Capabilities Develop A Suite of Tools for Circuit Manipulation Link Neuronal Activity to Behavior Integrate Theory, Modeling, Statistics, and Computation with Experimentation Delineate Mechanisms Underlying Human Imaging Technologies Create Mechanisms to Enable Collection of Human Data Disseminate Knowledge and Training
24 Major Opportunities for Biomedical Research Apply breakthrough knowledge and technologies to enhance understanding of biology and disease Translate basic science into better treatments Improve health care through science Sharpen focus on global health Reinvigorate the biomedical research community
25 Disorders with Known Molecular Basis with therapy Source: Online Mendelian Inheritance in Man, Morbid Anatomy of the Human Genome
26 Treating Rare Diseases: NOMID
27 National Center for Advancing Translational Sciences (NCATS) Mission: To catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions.
28 An early NCATS Project: Human Tissue Chip for Drug Screening Goal: develop biochip to screen for safe, effective drugs Use to predict toxicity, replace animal testing Use to predict efficacy Liver, heart, lung, other cell types Designed for multiple different readouts Twelve projects develop 3-D cellular microsystems representing human organ systems Seven projects explore potential of stem cells to differentiate into multiple cell types
29 Brain-Machine Interface Exoskeleton Paralysis affects ~6 million in U.S., more worldwide June 12, FIFA World Cup opening ceremonies Young Brazilian paraplegic will attempt to kick first ball Mechanical exoskeleton controlled by brain-computer interface Builds upon >20 yrs of neurobiology research by Miguel Nicolelis Work jointly supported by U.S. and Brazil More than $13.5M basic neuroscience research funding by NIH, including NIH Director s Pioneer Award Exoskeleton development and clinical research by Brazilian funders, including FINEP
30 Science Breakthrough of the Year (2013) What stops the body from waging its own war on cancer? New approaches unleash the power of the immune system to search and destroy cancer cells Blocking protein receptors that hinder immune response CTLA-4 Anti-PD [programmed death] 1 Genetically engineering immune cells to target tumor cells
31
32 Universal Flu Vaccine Virus surface protein from three flu strains Head Stem Head Stem
33 Universal Flu Vaccine Virus surface protein from three flu strains Head Stem
34 Major Opportunities for Biomedical Research Apply breakthrough knowledge and technologies to enhance understanding of biology and disease Translate basic science into better treatments Improve health care through science Sharpen focus on global health Reinvigorate the biomedical research community
35 Global Collaborations to Determine Best Treatments: ISCHEMIA Ischemic heart disease (IHD): leading cause of death and disability worldwide 7.2 million deaths annually >100,000 in Brazil ~450,000 in U.S. ISCHEMIA : International Study of Comparative Health Effectiveness with Medical and Invasive Approaches Led by NIH s National Heart, Lung, and Blood Institute Collaboration with researchers at 400 sites in 33 countries Including 24 sites in Brazil
36 ISCHEMIA: Brazilian Principle Investigators and Sites Doctor Institution City M. Abreu Instituto de Pesquisa e Estudos Médicos de Itajaí (IPEMI) Itajai M. Andrade Hospital da Bahia Pituba P. Caramori Hospital São Lucas da Pontificia Universidade Catolica do Rio Grande do Sol Porto Alegre A. C. Carvalho Universidade Federal de São Paulo São Paulo O. Coelho-Filho Universidade Estadual de Campinas Campinas C. Costantini Hospital Cardiológico Costantini Curitiba F. Dall Orto Hospital Maternidade e Pronto Socorro Santa Lucia Pocos de Caldas A. de Quadros Instituto de Cardiologia de Porto Alegre Porto Alegre W. Hueb Instituto do Coração da Universidade de São Paulo São Paulo J. Marin-Neto Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto Ribeirao Preto C. Mesquita Hospital Pró-Cardíaco Botafogo L. Miola Instituto de Moléstias Cardiovasculares São José do Rio Preto I. Nascimento CEU Diagnosticos Belo Horizonte P. Oliveira Instituto Nacional de Cardiologia Laranjeiras Rio de Janeiro C. Polanczyk Hospital de Clinicas de Porto Alegre Porto Alegre A. Rabelo Alves, Jr. Fundacao Bahiana de Cardilogia Salvador G. Reis Hospital Evangélico de Belo Horizonte Belo Horizonte E. Ribeiro da Silva Hospital TotalCor São Paulo L. Ritt Instituto Cárdio Pulmonar Salvador W. C. Rosa Hospital Universitário Cassiano Antonio de Moraes (Hucam) Vitoria J. F. Saraiva Hospital e Maternidade Celso Pierro São Paulo P. Smanio Instituto Dante Pazzanese de Cardiologia São Paulo R. Tumelero Hospital São Vicente de Paulo Passo Fundo J. Vitola Quanta Diagnóstico e Terapia Curitiba For more information contact Country Leader: Dr. A.C. Carvalho
37 Global Collaborations to Determine Best Treatments: ISCHEMIA Compares effectiveness of two initial treatment strategies for patients with stable IHD Conservative: Optimal Medical Therapy (OMT) with cardiac catheterization and revascularization for OMT failure and event Invasive: Cardiac Catheterization with optimal revascularization and OMT Enrollment: ,000 patients with at least moderate ischemia 1,000 with Chronic Kidney Disease, including dialysis patients
38 Major Opportunities for Medical Research Apply breakthrough knowledge and technologies to enhance understanding of biology and disease Translate basic science into better treatments Improve health care through science Sharpen focus on global health Reinvigorate the biomedical research community
39 Antimicrobial Resistance (AMR) A Growing, Global and Local Challenge
40 Antimicrobial Resistance (AMR) A Growing, Global and Local Challenge Patient: 35-year-old man from São Paulo Bloodstream infection caused by strain of methicillin-resistant Staphylococcus aureus (MRSA) susceptible to vancomycin (designated BR-VSSA) During antibiotic therapy, strain acquired vana gene cluster; became resistant to vancomycin (designated BR-VRSA) NIH-supported, global effort to identify BR-VRSA Finds new strain: with novel transferable vana plasmid Flávia Rossi, M.D. Thais S.R. Di Gioia, M.D. André Doi, M.D. Denise Brandão, M.D. Inneke Marie van der Heijden, Ph.D. Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo
41 Announcing today: A new FAPESP and NIH collaboration to identify new antifungal agents -- Consider Brazilian ants that farm fungus -- Other invasive fungi threaten the farm -- Ants have evolved a unique strategy -- Exocrine glands in exoskeleton harbor bacteria that produce antifungal compounds that kill the invasive species -- Could be an unprecedented source of new antifungal agents -- Possibly also for cancer and leishmaniasis -- Research project led by Jon Clardy, Harvard Monica Tallarico Pupo, USP -- Part of the International Cooperative Biodiversity Groups program
42 Major Opportunities for Medical Research Apply breakthrough knowledge and technologies to enhance understanding of biology and disease Translate basic science into better treatments Improve health care through science Sharpen focus on global health Reinvigorate the biomedical research community
43 Science without Borders: NIH-CNPq Visiting Fellows Program Supports postdocs from Brazil at NIH NIH program with the Brazil National Council for Scientific and Technological Development (CNPq) started in 2012 Part of Brazil s Science without Borders initiative CNPq support includes One-half stipend for 2 years Travel costs back to Brazil each year NIH support includes Written letter of commitment from selected NIH investigator Balance of NIH stipend amount Postdoctoral training Trains next generation of biomedical researchers and encourages long-term research partnerships
44 As for the future, your task is not to foresee it, but to enable it. ~ Antoine de Saint Exupéry
45 NIH Turning Discovery Into Health
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