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Research in Medicine

Research in Medicine. Roberto Adachi, MD Associate Professor Department of Pulmonary Medicine The University of Texas MD Anderson Cancer Center. Frases usadas por mis alumnos de medicina luego de completar sus proyectos en el laboratorio:.

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Research in Medicine

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  1. Research in Medicine Roberto Adachi, MD Associate ProfessorDepartment of Pulmonary MedicineThe University of Texas MD Anderson Cancer Center

  2. Frases usadas por mis alumnos de medicina luego de completar sus proyectos en el laboratorio: • Me siento parte del “puente” entre ciencias básicas y medicina • Por fin entiendo éste artículo • Comprendo la diferencia entre saber qué hacer con el paciente, y saber por qué hacerlo • Nunca aprendí en la escuela la disciplina mental para planear, ejecutar y publicar un proyecto • Es la única disciplina en que trato de probarme a mí mismo que estoy equivocado • He adquirido un instrumento que lo puedo aplicar al resto de mi vida • Investigación me “cambió” el cerebro • Creo que soy un mejor médico • Por fin me gusta Medicina • Esto ha sido lo más divertido de mi vida

  3. MDACC – TEC Monterrey • Summer Research Medicine Basic Sciences 2005 95 Medicine Clinical Research 2016 2 Engineering Basic Sciences 2011 9 • Elective Rotations Medicine Basic Sciences 2008 15(3 months) Medicine Clinical Research 2015 1 Medicine Clinical Medicine 2010 0 Engineering Basic Sciences 2011 1 • Research Rotations Medicine Basic Sciences 2009 16(1 year) Medicine Clinical Research 2016 0 Engineering Basic Sciences 2011 1 • Master/Graduate PhD, MD/PhD Basic Sciences 2013 2(2-3 years) MS Basic Sciences 2017 0 MPH Clinical Research 2017 0 • Post-doctoral Associates MD or PhD Basic Sciences 2004 15(2-3 years) TOTAL 157 • Scientific Publications 21 • Scientific Abstracts 67 • Academic Positions 3

  4. Texas Medical Center • Member Institutions 54 • Hospitals 21 • Schools/Universities 22 • Other 11 • Buildings 290 • 4.6 million m2 6 Km2 • Employees 106,000 • Advanced degree 20,000 • Students 70,000/y • Hospital beds 9,200 • Patient visits 8 million/y • Visitors 160,000/d • Budget $20 billion/y • Research $2.8 billion/y

  5. M.D. Anderson Cancer Center • Buildings 25 • Employees 19,000 • Faculty 1,700 • Trainees 6,300/y • Hospital beds 650 • Admissions 28,000/y • Patient visits 1.4 million • Clinical Protocols 1,100 • Research funds $740 million/y • Net Revenue $4.4 billion/y • Other Locations • Houston 8USA 14International 3

  6. DNA Technology • Recombinant DNA Technology • Solid phase DNA synthesis • Restriction endonucleases • Polymerases • Ligases • PCR • Transfection/transformation • Transgenic technologies • DNA sequencing • Genome sequencing • Genome Engineering • Oligonucletide-directed damage/cleavage • Peptide nucleic acid-directed damage/cleavage • Self-splicing introns • Zinc-finger nucleases (ZFNs) • Transcription activator-like effector nucleases (TALENs) • CRISPR/Cas9

  7. Genome Engineering

  8. CRISPR-Cas9 CRISPR Clustered Regularly Interspaced Short Palindromic Repeats Cas9 CRISPR Associated Nuclease 9 crRNA CRISPR RNA tracrRNA Trans-activating CRISPR RNA sgRNA Single guide RNA (engineered dual crRNA:tracrRNA) PAM Protospacer adjacent motif

  9. CRISPR History

  10. CRISPR History

  11. CRISPR History

  12. CRISPR Immunity

  13. CRISPR System

  14. Genome Engineering

  15. CRISPR Variants

  16. CRISPR Variants • Effector Domains • Transcription repression • Transcription promotion • Fluorescent reporter • DNA modification: methylase • Histone modification: acetylase • Recombinase • Scaffolding • Genomic Switch • Chemical switch • Light switch

  17. CRISPR Applications – Bacteria / Viruses • Bacterial genotyping • Strain phylogeny, genetic trajectory • Epidemiology, outbreak investigation, industrial surveillance • Anti-viral effects • Virus resistance in industrial cultures • Destruction of proviruses • Destruction of genome-integrated viruses • Anti-plasmid effects • Vaccinate bacteria against virulence factors • Vaccinate bacteria against antibiotic resistance elements • Decrease bacterial plasticity (e.g., transposons) • Integrity and stability of industrial bacteria

  18. CRISPR Applications – Eukaryotes • Genomic editing • “Easy” trangenics • Breaking the “mouse barrier” • Neuropsychiatric models • Modify many genes simultaneously • Model polygenic diseases • Multiplex analysis • Reverse genomics • Analysis of entire pathways • Refinement of GWAS data • Resistance to infections • Gene therapy • Chromosomal rearrangement in cancer • Driver vs passenger mutations in cancer • Synthetic lethality in cancer • CAR-T cell therapy • GMO commercial crops, home plants • GMO cattle, fish, pets • Synthetic biology • Directed evolution • Engineered ecosystems (gene drive)

  19. CRISPR Applications – Effector Fusion • Transcription repression and promotion • Alter expression of many genes • Mimic most diseases • Fluorescent reporter • Chromosomal imaging of repetitive genomic elements • Chromosomal dynamics • DNA modification, Histone modification • Epigenomics • Recombinase • Precise translocations • Forced chromosomal dynamics • Scaffolding • Too many possibilities • Genomic switch

  20. Resistance to Infections

  21. Gene Drive

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