CAN WE DEVELOP A COHERENT STRATEGIC FRAMEWORK FOR BIOMEDICAL
RESEARCH?
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GLOBAL Public Health Challenges Acute to Chronic Conditions
Health Disparities Emerging and Re-emerging infectious Diseases
Aging Population Emerging Non communicable diseases
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Orders of magnitude more effective Expensive in financial and
disability costs Understanding preclinical molecular events and
ability to detect patients at risk Did not understand the molecular
and cellular events that lead to disease Intervene before symptoms
appear and preserve normal function for as long as possible Treat
disease when symptoms appear and normal function is lost 21 st
Century20 th Century Need to Transform Medical Research in the 21st
Century
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Fundamental Roadblocks in Research and Development Basic
Research Biology Target ID Target Valid. Chemistry Screening
Optimization Development Pre-clinical Ind. Discov. Clinical Some
opportunities for improvement Biomarkers, Animal models, Systems
biology, Chemical genomics Biomarkers, Animal models, Systems
biology, Chemical genomics Examples of key roadblocks Validation of
complex diseases Biomarkers, Clinical training, Regulatory
harmonization, Informatics Insufficient read-out on safety and
toxicology Lack of standardization and efficiency of clinical
trials Biomarkers, Animal models, Data sharing Biomarkers, Animal
models, Data sharing
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What is the NIH Roadmap for Medical Research? A framework of
scientific priorities that the NIH as a whole must address in order
to optimize its entire research portfolio. A vision for a more
efficient, innovative and productive system of research into
health, mechanisms of disease, and related behaviors.
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The NIH Roadmap for Medical Research Re-engineering the
Clinical Research Enterprise Research Teams of the Future New
Pathways to Discovery
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Complexity of Biological Networks Multiple levels of cross-talk
between molecular pathways Multiple levels of cross-talk between
molecular pathways Many molecular targets part of intricate
signaling networks Many molecular targets part of intricate
signaling networks Novel experimental and theoretical concepts
neededNovel experimental and theoretical concepts needed
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Complexity of Biological Networks
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All molecules are created equal, but some are more equal than
others. Animal Pharm* *Adapted from George Orwells Animal Farm
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Biological Data of the Future CurrentFuture
DestructiveNon-Destructive QualitativeQuantitative
Uni-DimensionalMulti-Dimensional Low Temporal Resolution High
Temporal Resolution Non-localizedSpatially resolved Low data
densityHigh data density Variable standardsCommon standards
Non-CumulativeCumulative
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Combining Functional Imaging with GFP Linked Gene Expression 0
230 ml/gm 0 6.2 ml/gm.min MatLyLu tumor (430 mm3), capillary marked
by c Vascular volume Permeability c c NCI P20 CA86346 Pre-ICMIC
Program at JHU-RADIOLOGY GFP expression c
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MOLECULAR NANOMACHINES Architecture of an 11,000 kDa Pyruvate
Dehydrogenase Complex 475 J. Milne and S. Subramaniam, National
Cancer Institute, NIH
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High Field MRI of White Matter Tract Development in Mouse
Embryos ic st White matter reconstruction studies of a mouse brain
at embryonic day 16 (ex vivo)
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Solving the Puzzle of Complex Diseases and Conditions
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Obesity: A Worldwide Issue Obesity Health Risks Cancer Diabetes
Hyper- tension Gall- bladder Disease Kidney Failure Stroke Heart
Failure Athero- scleroris
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New Discoveries in Obesity Research Using RNA Interference
(RNAi) 112 genes 305 genes Normal Worm Obese Worm Thin Worm Source:
Ashrafi et. al., Nature, Vol. 421, pp. 268-272.
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Human Genome Project and HapMap Are Complete: Where Do We Go
From Here? Plummeting cost of DNA sequencing New discoveries
accelerating revolution of the practice of medicine Genes,
Environment, and Health Initiative Identify roots of 10 most common
diseases Devise new ways of monitoring personal environmental
exposures
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Advances in Age-related Macular Degeneration (AMD) AMD is the
leading cause of blindness in people over age 60 Variations in
certain genes involved in inflammation can predict the risk of
developing AMD 56 % of the unaffected individuals had a variant
that conferred protection to AMD 74 % of those with AMD had no
protective variants Vision affected by AMD Normal vision
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Predict which patients need chemotherapy Impact: 100,000 women
each year can make a more informed choice 70,000 women do not have
to undergo chemotherapy Reduces routine cost of treating these
patients For each patient year of life gained, we save ~$8,000 Test
tumor samples for mutations in these genes New Discoveries Make it
Possible to Personalize Cancer Treatment Identified 16 informative
genes
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Pharmaco-Genomics: Managing Human Variability Pharmaco-Genetics
Research Network (PGRN) National collaboration of scientists
studying the effect of genes on people's responses to a wide
variety of medicines Pharmaco-Genetics & Pharmaco-Genomics
Knowedge Database (PharmGKB) Integrated knowledge base for
pharmacogenetics linking phenotypes and genotypes
http://www.nigms.nih.gov/Initiatives
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Systems biology Animal models Target ID & Validation
Fundamental R & D Strong Bioethics and Privacy regulations
Harmonization Harmonization of policies and regulations Training
Pharmacogenetics Networks NECTAR Biomarkers Target identification
and validation Predictive toxicology Iterative chemistry New
Pathways to Discovery SCIENTIFIC FOCUS AREAS Research Teams of the
Future Translational Centers Public Trust PracticePhases
I-IIIPreclinical Screening/ Optimization
BasicTranslationalClinical
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The Future Paradigm: Transform Medicine from Curative to
Preemptive Preemptive Personalized Predictive NIH research
initiatives and programs are aiming to transform the practice of
medicine as we know it.
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Meeting World Health Problems: The Need for Sound Program
Planning With the true spirit of cooperation, with the basic
understanding of needs, and with the efforts of enlightened groups
everywhere, we can push forward to new frontiers of world health
and well-being. Dr. Joseph W. Mountin (1952) Founder of CDC