Zhang: Looking for other single-subunit classII Cas-type enzymes. Cpf1 found '15 Cell https://t.co/zGnVwfjyQD #AACR16
12:12pm April 17th 2016 via Hootsuite
Zhang: Another tool - to discover new enzymes; either class 1 multiprot complex for RNA guides); class 2 is single-subunit (Cas9) #AACR16
12:10pm April 17th 2016 via Hootsuite
Zhang: Target a gene, bash the non-coding region (saturating mutagenesis), can ID novel transcription factor binding sites #AACR16
12:09pm April 17th 2016 via Hootsuite
Zhang: Can ID genes that drive resistance, can rapidly ID new targets. Can also target non-coding RNAs. #AACR16
12:07pm April 17th 2016 via Hootsuite
Zhang: CRISPR knockout ,for melanoma tested. Used SAM for GoF screening genome-wide '15 Nature https://t.co/O1GfQzi6zT #AACR16
12:05pm April 17th 2016 via Hootsuite
Zhang: Can do loss of fn, or gain-of-fn screens. Melanoma, vemurafenib tragets V600E mutant BRAF. Selection pressure (Wagel figure) #AACR16
12:03pm April 17th 2016 via Hootsuite
Zhang: Similar to shRNA, can generate large #'s of guide RNAs. Cloned, lentivirus library, transduce, enrich for phenotype #AACR16
12:02pm April 17th 2016 via Hootsuite
Zhang: But can also use to localize effectors - turn genes on/off, add fluorescent tags. #AACR16
12:01pm April 17th 2016 via Hootsuite
Zhang: Short RNA guides as a protetion system. Recent review https://t.co/cmlbzbLCFg Shows Cas9, harness cleavage #AACR16
12:00pm April 17th 2016 via Hootsuite
Zhang: Homology-directed repair (HDR), only for cells that undergo replication. ZfN, TALes, CRISPR is found in 60% bact cells #AACR16
11:58am April 17th 2016 via Hootsuite
Zhang: Hisotry - Haber (Brandeis) and Jasin (MSKCC) NHEJ or HDR from DSB. NHEJ can introduce indels, lead to loss of fn #AACR16
11:57am April 17th 2016 via Hootsuite
Feng Zhang (Broad Inst MA) "Genome editing using CRISPR-Cas systems" #AACR16
11:56am April 17th 2016 via Hootsuite
.@BBethJo You bet. Alas due to new responsibilities coverage over twitter won't be as complete as prior years... will do what I can.
11:53am April 17th 2016 via Hootsuite in reply to BBethJo
Bradner: BRD4 inh and TNBC '16 Nature https://t.co/iN2hT1dJxY Can BRD4 be degraded? #AACR16
11:51am April 17th 2016 via Hootsuite
RT @CMullighan: Outstanding talk from @jaybradner on epigenetics and BRD4 targeting in cancer #AACR16
11:48am April 17th 2016 via Hootsuite
Bradner: MYC regulates antitumor resp via CD47 and PD-L1 '16 Science https://t.co/cKZvxxMPYB Epigenomic Rx supporting immunoRx #AACR16
Bradner: Also target a MYC-specific dependency, developed compound (RG-6146 - TEN-010) for secondary AML, and chemorefrac DLBCL. #AACR16
11:45am April 17th 2016 via Hootsuite
Bradner: Shows imaging of a 33yo, regression with BET-rearr carcinoma, reasons for optimism #AACR16
11:43am April 17th 2016 via Hootsuite
Bradner: Clinical translation, with Tensha Therapeutics, modifications of JQ1. BRD4 rearr in lung ca #AACR16
11:42am April 17th 2016 via Hootsuite
Bradner: Created a model, found LMX1A in meduloblastoma, tracing back through development, cell of origin #AACR16
11:40am April 17th 2016 via Hootsuite
Bradner: Super-enhancers are proto-oncogene. Origins of super enh '16 Nature https://t.co/dLk0PXFibW finding master switches #AACR16
11:39am April 17th 2016 via Hootsuite
Bradner: The idea - to get cancer cells to forget they are cancer. Work on super-enhancers https://t.co/ahjEf65QhD #AACR16
11:37am April 17th 2016 via Hootsuite
Bradner: Shows 3D model of active pocket, large interaction space. '10 Nature https://t.co/bR3WlDCFl8 ID small molecule #AACR16
11:35am April 17th 2016 via Hootsuite
Bradner: Bromo-domains: MYC doesn't act alone - brings to sites many factors, like lysine histone acetyltransferases. Brd4 #AACR16
11:32am April 17th 2016 via Hootsuite
Bradner: Cancer epigenetics 'is exploding'. Factors appearing as important dependencies. Writers, erasers, and readers. #AACR16
11:31am April 17th 2016 via Hootsuite
Bradner: Shows list of transcription factors (MYC, TP53, nfKb, b-catenin), chromatin factors. #AACR16
11:29am April 17th 2016 via Hootsuite
James Bradner (Novartis MA) "Targeting epigenomic dependencies in cancer" #AACR16
11:27am April 17th 2016 via Hootsuite
Mardis: 2nd met 12.9K muts, 3.6k exp, 1.4K pred. neoantigens. Shows evolving immune response of CD3/4/8 infiltration met2-met3 #AACR16
11:24am April 17th 2016 via Hootsuite
Mardis:Primary and 2 mets deeply analyzed, showing a clonal evol diagram, from high to 'even more complexity' and 3rd simple #AACR16
11:22am April 17th 2016 via Hootsuite
Mardis: Another (unpub) example: GBM, rapid progression in CNS, did Foundation test w/high mut load, polE mut germline status #AACR16
11:21am April 17th 2016 via Hootsuite
Mardis: Another example, temporal prog in pediatric ependymoma, shows for surgeries, complex landscape, neoepitope candidates #AACR16
11:20am April 17th 2016 via Hootsuite
Mardis: Relapse of TNBC during 18mos - 2y, measuring outcome of trial #AACR16
11:19am April 17th 2016 via Hootsuite
Mardis: At end of s6 month: either synthetic long peptide, or polyepitope DNA vaccine / electroporation #AACR16
11:18am April 17th 2016 via Hootsuite
Mardis: Are working with Komen Promise TNBC personalized vaccine trial; a 'window of oppy' trial design during first 6mo #AACR16
11:17am April 17th 2016 via Hootsuite
RT @hemedoc: #AACR16 Mardis: altho lrg # of muts ID'd, only a small # will be exp.and be presentable by specific HLA https://t.co/0iLLsmozPD
11:16am April 17th 2016 via Hootsuite
Mardis: Pre- and post-vaccine, shows pt specific dendritic cell response (via flow), showed safety, partial resp of CD8+ T-cell #AACR16
11:15am April 17th 2016 via Hootsuite
Mardis: Busy fig. from paper - overall burden of muts from 200-500, able to winnow down to 11-15 via HLA and HLA exp. overlap #AACR16
11:14am April 17th 2016 via Hootsuite
Mardis: RNA - mutated genes and expressed. First-in-human: https://t.co/7NN4FmBygZ all BRAF+, used netMHC algorith., refined #AACR16
11:11am April 17th 2016 via Hootsuite
Mardis: Neoantigen work: use genomic data to design vaccines or predict neoantigen load. Use NGS, HLA haplotypes, RNA data #AACR16
11:10am April 17th 2016 via Hootsuite
Mardis: Recent TCGA work 12 ca types, fn implications of rare germline '15 Nature Comm https://t.co/qvmJcn64hS #AACR16
11:09am April 17th 2016 via Hootsuite
Mardis: Germline in pediatric ca - '15 NEJM https://t.co/iN0y3xuODW n=1120, about 9% prevalence #AACR16
11:08am April 17th 2016 via Hootsuite
Mardis: 10K pts referred '15 ref https://t.co/67MG0yfB0k molecular Dx in 9% of tested. #AACR16
11:06am April 17th 2016 via Hootsuite
Mardis: Also Project Genie https://t.co/tOczbNPH8F another important resource #AACR16
11:04am April 17th 2016 via Hootsuite
Mardis: Points to this WashU tool of curated cancer variants CIViC https://t.co/zgES5vtJQ5 #AACR16
Mardis: Shows major subtypes figure from this '15 Cell https://t.co/nZ1WiC3zdI including the Triple-WT subtype #AACR16
11:03am April 17th 2016 via Hootsuite
Mardis:ALK fusions - Crizotinib, ceritinib Rx. BRAF 2%, but in cutaneous melanomas are driven by BRAF #AACR16
11:01am April 17th 2016 via Hootsuite
Mardis: Best known lung adeno: EGFR (15%), after biopsy, Iressa, Tarceva, Erlotinib targeted Rx '05, in '15 approved first-line Rx #AACR16
11:00am April 17th 2016 via Hootsuite
Mardis: Focus on Rx targets - in lung adenocarcinoma, pie-chart of genes showing KRAS, EGFR, EML4-ALK, HER2 etc. and impact #AACR16
10:59am April 17th 2016 via Hootsuite
Mardis: Points to first NGS WGS Ley https://t.co/8IlJAQUzuu Now global efforts (eg ICGC) and pan-cancer analysis #AACR16
10:57am April 17th 2016 via Hootsuite
Mardis: 4 topics: Cancer genomics discovery; ID Rx targets; role of germline suscept; genome-guided immunoRx and precision vaccines #AACR16
10:54am April 17th 2016 via Hootsuite
