RT @atulbutte: Flying cars… finally coming soon? https://t.co/sES3gnEciJ
9:40pm February 22nd 2017 via Hootsuite
(Staudt: Here's a Scientific American piece about this project https://t.co/1OSo7N8EHW #Tricon )
8:13pm February 22nd 2017 via Hootsuite
(I found Lou Staudt's slides online https://t.co/LgdK4kzmmX #Tricon)
8:12pm February 22nd 2017 via Hootsuite
Staudt: Do culture conditions need optimization? For different organs and tumor types? Sensitivity to post-surgery handling? #Tricon
8:11pm February 22nd 2017 via Hootsuite
Staudt: How easy to perform in different labs? Proprietary reagents w/batch variability? #Tricon
8:10pm February 22nd 2017 via Hootsuite
Staudt: Do various culture methods favor different geneitc/epigenetic subpopulations w/in primary tumor? #Tricon
8:09pm February 22nd 2017 via Hootsuite
Staudt: Called a pilot: will genetic and epigenetic nature of primary tumor affect ability to be estab. in-vitro? #Tricon
8:08pm February 22nd 2017 via Hootsuite
Staudt: Primary biopsies sent to centers; link from site to center will be maintained to have some level of response to Rx #Tricon
8:06pm February 22nd 2017 via Hootsuite
Staudt: Models may also suggest novel Rx '14 Science https://t.co/JbK6MOfxdD #Tricon
8:05pm February 22nd 2017 via Hootsuite
Staudt: Keratin14 marker: cells invade mam gland, minority of popul'n, but invasion were all K14+ '13 Cell https://t.co/KcprYIyRhR #Tricon
8:02pm February 22nd 2017 via Hootsuite
Staudt: Models w/known drivers, recapitulate cell subtypes. Shows data of organoids '14 Cell in prostate ca https://t.co/t5zf6gGyu2 #Tricon
8:00pm February 22nd 2017 via Hootsuite
Staudt: Conditional reprogramming making it simpler, Wnt signalling '12 ref https://t.co/PonWxMwJan
7:58pm February 22nd 2017 via Hootsuite
Staudt: New tech - organoids from Clevers '11 ref https://t.co/XQ7TaQPWXU #Tricon
7:57pm February 22nd 2017 via Hootsuite
Staudt: Models for combinations of lesions do not exist; rare subtypes underrep or nonexistent; models don't recapitulate subpops #Tricon
7:56pm February 22nd 2017 via Hootsuite
Staudt: Cell lines do not have annotations that relate to primary tumor. Today know 'are suspect' genetically (i.e. prostate ca) #Tricon
7:55pm February 22nd 2017 via Hootsuite
Staudt: Combining structural with functional genomics. Unmet need: genetic analysis down to 0.5% (NTRK fusions), and most no models #Tricon
7:54pm February 22nd 2017 via Hootsuite
Staudt: Contracted with ATCC. Today we have correlative science; now want models. Putative driver genes, model, fn genomics #Tricon
7:53pm February 22nd 2017 via Hootsuite
Staudt: Working with Leidos, created a competition, w/Broad (Jesse Boehm), CSHL (Dave Tuveson), Univ Verona (Scarpa), Hubrect. #Tricon
7:51pm February 22nd 2017 via Hootsuite
Staudt: 3y from now is the end; Mike Stratton at Wellcome Trust/CRUK had the same idea; Hubrecht Inst ("HUB") Hans Clevers #Tricon
7:50pm February 22nd 2017 via Hootsuite
Staudt: Full genomic characterization; clinical annotation, including resp to last Rx. A scaleable effort #Tricon
7:49pm February 22nd 2017 via Hootsuite
Staudt: Goal - create 1000 new cancer cell lines; a 'project so good people wouldn't complain that there is less R01 money' #Tricon
7:48pm February 22nd 2017 via Hootsuite
Lou Staudt (NCI MD) The human cancer model initiative #Tricon
Dow: Shows time-lapse of 3d growth, with and without Rsponding w/ and post-Dox. #Tricon
7:26pm February 22nd 2017 via Hootsuite
Dow: Can be taken out, regrown in 3D Matrigel. No serum req'd but requires EGF, Noggin, Rspondin1 factors. #Tricon
7:25pm February 22nd 2017 via Hootsuite
Dow: Also MB size Ptprk-Rspo3 inversion, showed 3 color FISH. Inducible mice, made organoids, can harvest intestinal crypts #Tricon
Dow: Fusion partner up-regulated, likely the driving event. EIF3E-RSPO2 (R-spondin) fusion engineered, shows data #Tricon
7:24pm February 22nd 2017 via Hootsuite
Dow: >95% of clones had biallelic loss. Could multiplex, have gone up to six guide RNAs.'12 ref https://t.co/QHI6BH81pa #Tricon
7:22pm February 22nd 2017 via Hootsuite
Dow: Induceable Cas9 w/GFP; can target APC and APC/p53. Shows expression loss and in vivo loss of protein #Tricon
7:21pm February 22nd 2017 via Hootsuite
Dow: Many components altered, extra cellular down to nuclear effect. HDR and NHEJ; they use NHEJ for large translocation engineering #Tricon
7:20pm February 22nd 2017 via Hootsuite
Dow: Want to better model human biology. APC drivent by Wnt ligand; bind receptors, beta-catenin stabilized, drives c-Myc others #Tricon
7:18pm February 22nd 2017 via Hootsuite
Dow:CR cancer: 1.4M new cases, 700K deaths ww; 85% carry APC ts. Models do not recapitulate human CRC biology #Tricon
7:17pm February 22nd 2017 via Hootsuite
Lukas Dow (Weill Cornell NY) Tailored pre-clinical models with CRISPR-based genome editing #Tricon
7:16pm February 22nd 2017 via Hootsuite
Q: G12C not scoring highly; connection to particular ts? Winslow: P53del, RASdel data supports; lung ca is smoking-driven thus G12C #Tricon
7:15pm February 22nd 2017 via Hootsuite
Winslow: Have used models for 10y but genotype-spec biology w/phenotype, drug response, lots of time and resources. CRISPR efficient #Tricon
7:10pm February 22nd 2017 via Hootsuite
Winslow: Tumors induced by HDR in KRAS, shows cancer cell #'s of G1R, G12D, G12R over logs of cell numbers #Tricon
7:05pm February 22nd 2017 via Hootsuite
Winslow: AAV vector delivered; 4-10 months, showed lung imaging and H&E stains. Looked across 50 tumors; showed G12D/V/R prev #Tricon
7:04pm February 22nd 2017 via Hootsuite
Winslow: Created a panel of KRAS codon 12/13 mutations, in equal proportions, see % of tumors formed. #Tricon
7:03pm February 22nd 2017 via Hootsuite
Winslow: CRISPR causes ds breaks; can do HDR with mutation. Created template in AAV HDR template to repair RAS allele #Tricon
7:02pm February 22nd 2017 via Hootsuite
Winslow: Oncogenic mutations - highlights KRAS, 'all studies use G12D', but they may have different effects on phenotype, drug resp #Tricon
7:01pm February 22nd 2017 via Hootsuite
Winslow: There are many coincident tumor suppressor mutations. P53 for example; distibution w/LKB1mut is different #Tricon
6:58pm February 22nd 2017 via Hootsuite
Winslow: Shows data - relative size as a percentile; Lkb1 had the highest effect Setd2 next one (chr regulator) #Tricon
6:56pm February 22nd 2017 via Hootsuite
Winslow: Can look at the effect of deleting all these ts genes. Shows lung lobe with a lot of tumors; H&E stain also shown #Tricon
6:55pm February 22nd 2017 via Hootsuite
Winslow: Took 11 tumor suppressors, each guide RNA has an ID, and each tumor has a barcode. Reading genotype and size #Tricon
6:54pm February 22nd 2017 via Hootsuite
Winslow: The whole lung, grind it up, and quantify each cell # from a bulk tumor. #Tricon
6:53pm February 22nd 2017 via Hootsuite
Winslow: Use lentiviral vectors; stable integration; library w/1M barcodes, so each infected cell is labeled. #Tricon
Winslow: Put diverse genotypes into one mouse; replacing floxed alleles with CRISPR 'a few thousand tumors' #Tricon
6:52pm February 22nd 2017 via Hootsuite
Winslow: Many tumor suppressors - long list from TCGA in lung adenocarcinomas. Able to inactivate genes, lentiviral sgRNAs #Tricon
6:51pm February 22nd 2017 via Hootsuite
Winslow: Also poor quantification of tumor response (in vivo imaging, histology) #Tricon
6:49pm February 22nd 2017 via Hootsuite
Winslow: Major limitation for Cre/Lox engineered mouse models for translation - limited diversity; diificult to scale-up #Tricon
Monte Winslow (Stanford Univ CA) Cancer modeling with in vivo CRISPR/Cas9 genome editing #Tricon
6:47pm February 22nd 2017 via Hootsuite
