Eric Kmiec
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Re-engineering genomes using single stranded oligonucleotides and TAL- effector Nucleases (TALENs) for industrial technology Dr. Eric B. Kmiec Center for Translational Cancer Research Helen F. Graham Cancer Center Christiana Hospital and Delaware State University
Transcript of Eric Kmiec
Re-engineering genomes using single stranded oligonucleotides and TAL-
effector Nucleases (TALENs) for industrial technology
Dr. Eric B. Kmiec
Center for Translational Cancer Research Helen F. Graham Cancer Center
Christiana Hospitaland
Delaware State University
Pure basic research(Bohr)
Use-inspired basic research(Pasteur)
Pure applied research(Edison)
“Pasteur’s Quadrant”
High
High
Low
Low
Quest for Fundamental
Understanding
Consideration of UseStokes, Donald. Pasteur's Quadrant Basic Science and Technology Innovation. Washington, DC: Brookings Institution Press, 1997. Print.
ssODN
ZFN
TALEN
Technologies and Tools
Gene Editing
CRISPR/Cas9
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Kim, H., Kim, J. A guide to genome engineering with programmable nucleases. Nature Review Genetics doi:10.1038/nrg3686 (2014)
Gene-Editing Model System
Regulation of Gene Editing
Oligonucleotide Enters Cell
Aligns in Homologous Register at Target Site
Creates D-loop
DNA Replication Activity
Transcriptional Activity
Homeologous Recombination
Activates DNA Damage Response Pathway
p53P
ATMP/ATRP
CHK1/CHK2P
Activation
Cell Cycle Delay (S)S phase stalling
H2AXP DS-BreakRepair
Coordinates Repair and Restart of Fork
Replication stallingFork Collapse
DS-Breaks
Incorporates into Target Site : replaces mutant
sequence
Gene conversion via Transcription-Coupled Repair
Gene conversion via Mismatch Repair
DNA Damage Elevates Gene
Editing Frequency
BLMHelicase
and/or
and/or
DNA Pairing Activity
RAD51(etc)
CellSurvival
The Kmiec Laboratory
2000-2011 Graduate StudentsHetal Parekh-Olmedo, Ph.D.Erin Brachman, Ph.D.Miya Drury, Ph.D.Luciana Ferrara, Ph.D.Katie McGuire, Ph.D.Julia Engstrom, Ph.D.Jennifer Sonntag, Ph.D.Kerry Falgowski, Ph.D.Jennifer Illuzzi, Ph.D.Melissa Bonner, Ph.D.Timothy Swartz, Ph.D.
Rohina NiamatBryan StrousePawel BialkNatalia RiveraShani SamuelBrett Sansbury
1995-2000 Graduate StudentsJoanne Sekiguchi, Ph.D.Allyson Cole-Strauss, Ph.D.Hideohito Kotani, Ph.D. Seema Dutta, Ph.D. Ronald Myers, Ph.D.
Postdoctoral FellowsDavid Gerhold,Ph.D.Kyggeon Yoon, Ph.D.
Postdoctoral FellowsSubhais Sandu, Ph.D.Dula Man, Ph.D
