Reminder: Campus Stem Cell Seminar Series - Tomorrow, Tuesday Sept. 17th
Tim Kamp
Hello all,
As a reminder, the next Stem Cell Seminar series will be held tomorrow, Tuesday September 17th – details below. Please note the change in location for this date.
Time: 12:00 pm – NOON
Location: UW Biotechnology Center Auditorium (425 Henry Mall, Rm. 1111)
Speaker: Divya Sinha, Ophthalmology, Assistant Scientist (GAMM LAB)
Topic: Mutation-specific responses to gene therapy in patient-specific iPSC model of autosomal dominant Best disease
Abstract: Best disease is an inherited disorder that leads to progressive and irreversible loss of central vision. It is caused by mutations in BESTROPHIN1 (BEST1) gene, which encodes a homo-pentameric calcium activated chloride channel (CaCC) in retinal pigment epithelium (RPE) cells within the retina. Over 200 mutations in BEST1 are known, majority of which are dominantly inherited. Given the lack of relevant animal models for autosomal dominant Best disease (adBD), we utilized induced pluripotent stem cell-derived RPE (iPSC-RPE) based disease model to assess therapeutic strategies. CaCC currents measured from adBD patient-specific iPSC-RPE were found to be significantly diminished when compared to wildtype and isogenic controls. Gene augmentation via viral expression of wild-type BEST1 restored CaCC to normal levels in iPSC-RPE where adBD was caused by mutations in ion binding regions, but not when caused by a mutation predicted to be localized to a structural region of the channel. Gene editing via CRISPR-Cas9 was used as an alternative approach to silence mutant allele in iPSC-RPE. Post-gene editing, iPSC-RPE from all adBD iPSC lines tested showed increase in CaCC current. Overall, our results using patient-specific iPSC-RPE show that gene augmentation is a feasible strategy for some adBD patients depending on the role of the mutated amino acid. Those missense mutations that are unresponsive to gene augmentation are candidates for gene editing. Importantly, in absence of suitable animal models, iPSC-RPE based Best disease model could be utilized as a preclinical testing platform.
Reminder: If you are talking this Seminar Series for credit, please check in with Hollie Thompson at the back of the room.
Next Seminar: On Tuesday, September 24th, Charu Mehta, SCRMC Trainee, Cell Regenerative Biology (Bresnick Lab), will be speaking on “RNA-Regulatory Exosome Complex Confers Hematopoietic Progenitor Survival.” ." This talk will be in the Wisconsin Institutes of Discovery (WID), H.F. Deluca Forum in the Town Center on the first floor (map), and will include sandwiches.
A list of the talks for the semester is found at:
https://stemcells.wisc.edu/campus-lab-meeting-schedule/
Thank you,
Hollie Thompson
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Administrator
Stem Cell and Regenerative Medicine Center
1111 Highland Avenue, STE 8457
p. 608-263-2982