Tlsty: These R1 cells can produce glial and neural progenitor cells, even adipocytes that produce cell-type spec genes #ncistg14
11:08am March 21st 2014 via Hootsuite
Tlsty: Novel marker not used before for stem cell selection; lineage promiscuity, cells with great potential. #ncistg14
11:07am March 21st 2014 via Hootsuite
Tlsty: Showed R1 rare cells can recapitulate the human mammary gland in a murine host. #ncistg14
11:06am March 21st 2014 via Hootsuite
Tlsty: Markers were CD90 / CD73; R1 to R4 quadrants as a fn of passage: R1 is 0.15% of population, can reconstitute tissue #ncistg14
11:05am March 21st 2014 via Hootsuite
Tlsty: FACS to isolate sub-populations from >100 healthy donors. 2013 PNAS ref: http://t.co/RUZHU8byCj #ncistg14
11:04am March 21st 2014 via Hootsuite
Tlsty: Chose Thy-1, 5-NED epitopes for membrane-assoc'd markers of +/- p16 in healthy mammary tissues #ncistg14
11:02am March 21st 2014 via Hootsuite
Tlsty: Stress-tolerant cells (p16 down) isolated, using exp profiling, found cell-surface markers toggled by p16 100-fold #ncistg14
11:01am March 21st 2014 via Hootsuite
Tlsty: Repressed p16: bypasses senescence, also uncouples centrosome duplication, confers epigen. plasticity #ncistg14
10:59am March 21st 2014 via Hootsuite
Tlsty: Arrest vs proliferation - what controls it? p16 repression can be mutated or reversible #ncistg14
10:58am March 21st 2014 via Hootsuite
Tlsty: ER+/- cells: A spectrum of resistance Transcription, translation, protein degradation, protein modifications: all fluctuate#ncistg14
10:56am March 21st 2014 via Hootsuite
Tlsty: Stochasticity - fluctuating protein levels, only seen at the single-cell level. Two different phenotypes from a single cell #ncistg14
10:55am March 21st 2014 via Hootsuite
Tlsty: Non-genetic hetergeneity, probably at the epigenome level. Adaptation, differentiation, ecology. #ncistg14
10:54am March 21st 2014 via Hootsuite
Tlsty: Characteristic of a complex adaptive system - self-organizing, system 'learns'... #ncistg14
10:52am March 21st 2014 via Hootsuite
Tlsty: Non-mutagenic process caused by physical and chemical stresses, causing hetergeneity #ncistg14
Thea Tlsty, University of California San Francisco: Stochastic Cellular States Associated with Malignancy #ncistg14
10:51am March 21st 2014 via Hootsuite
.@DrJackKruse I'm open to new perspectives but no thanks.
10:19am March 21st 2014 via Hootsuite in reply to
Markowitz: Risk allele of a PGDH promoter SNP to colorectal cancer; located in a small LD block Ref: http://t.co/BFckkGpaul #ncistg14
10:12am March 21st 2014 via Hootsuite
Markowitz: Nurses Health Study, from normal colon that went on to develop cancer, affect of aspirin Ref: http://t.co/AEXP7rXEDv #ncistg14
10:09am March 21st 2014 via Hootsuite
Markowitz: COX-2, Cyclin D1 induction, leading to colonic neoplasia, suppressed by 15-PGDH PNAS: http://t.co/l2955TfGX3 #ncistg14
10:04am March 21st 2014 via Hootsuite
Markowitz: Biochemistry of prostaglandins, lots of biology to signaling, from growth, migration, anti-apoptosis, angiogenesis #ncistg14
9:57am March 21st 2014 via Hootsuite
Markowitz: For CRC what's downstream? TGFb up-regulated, then colon cancers turn down? One gene: 15-PGDH #ncistg14
9:56am March 21st 2014 via Hootsuite
Markowitz: Work from '95 - '99: RII gene targeted with SMAD complex. Vogelstein's 2013 science review figure #ncistg14
9:55am March 21st 2014 via Hootsuite
Markowitz:Defect in mismatch repair, hotspot in TGF-beta RII mutations #ncistg14
9:53am March 21st 2014 via Hootsuite
Markowitz: 15-PDDH a metabolic tumor suppressor pathway that regulates colon cancer dev., suscept., & chemoprev. with NSAIDS #ncistg14
9:52am March 21st 2014 via Hootsuite
Sanford Markowitz, Case Western Reserve University: Genetic Pathways in Colon Cancer #ncistg14
9:51am March 21st 2014 via Hootsuite
Swanton:Two principles: decipher mechanisms of cancer diversity, and improve cancer selection pressures (targeting drivers) #ncistg14
9:45am March 21st 2014 via Hootsuite
Swanton: Genome doubling can occur in >60% some kinds of cancers. Tolerance of genome doubling can then have aneuploid tolerance #ncistg1
9:42am March 21st 2014 via Hootsuite
Swanton: Then genome doubled, then another round of chrom instability, #ncistg14
9:38am March 21st 2014 via Hootsuite
Swanton: NSCLC shared mut's illustrating a genome doubling event, EGFR RB1, PS3, all share instability. #ncistg14
Swanton: Trunk drivers, setting up a trial targeting clonally dominant drivers early on #ncistg14
9:36am March 21st 2014 via Hootsuite
Swanton: WES before drug therapy, and then focused gene panel after if therapy fails. See branched evolution, showing 8 samples #ncistg14
Swanton:Tracking non-small cell lung Cancer Evol through therapy ("TRACERx") #ncistg14
9:35am March 21st 2014 via Hootsuite
Swanton: Driver vs. passenger mutation profile terribly complex. There is a tumor sampling bias. #ncistg14
9:34am March 21st 2014 via Hootsuite
Swanton: 6 of 120 mutations occurring in only 2 genes, a SWI/SNF chromatin remodeling complex #ncistg14
9:30am March 21st 2014 via Hootsuite
Swanton: Then use a model to predict the 'trunk' mutation, looking at SETD2 changes across clonal evolution #ncistg14
9:29am March 21st 2014 via Hootsuite
Swanton: (5% vs. 40% was for P53) #ncistg14
9:28am March 21st 2014 via Hootsuite
Swanton: Est of driver prevalence from a single vs multiple biopsy: marked difference. 5% vs 40% #ncistg14
Swanton: Metastatic sites evolved through chromosomal instability, assoc'd with poor outcome. #ncistg14
9:25am March 21st 2014 via Hootsuite
Swanton: Ploidy analysis of primary nephrectormy cp to lung wall, very different allelic imbalance between the two #ncistg14
9:24am March 21st 2014 via Hootsuite
Swanton: Diag. of bottlenecking at metastatic sites - is there a subst. for diversity? #ncistg14
9:22am March 21st 2014 via Hootsuite
Swanton: 1960: macroevolution figure and quote - chromosomal structure, rearrangements, genome doubling etc. #ncistg14
9:21am March 21st 2014 via Hootsuite
Swanton: Challenge is cancer 'macroevolution'. Points to Goldschmidt book called 'hopeful monsters', rare events -> change #ncistg14
9:20am March 21st 2014 via Hootsuite
Swanton: Some complex tumors, illustrating very recent work in Nature Genetics ref: http://t.co/q1dSh0YOWR #ncistg14
9:19am March 21st 2014 via Hootsuite
Swanton: 1/3 of the mut's were non-synon. Showed branched evolution in ccRCC Ref: http://t.co/ME1mtg3JDy #ncistg14
9:18am March 21st 2014 via Hootsuite
Swanton: Implications of hetergeneity in cancer, ref: http://t.co/16vQ53WvFy #ncistg14
9:17am March 21st 2014 via Hootsuite
Charles Swanton, University College London. Tumour Heterogeneity and Cancer Evolution #ncistg14
9:16am March 21st 2014 via Hootsuite
Church: Original Cas9 Science paper had 190K guide RNAs, many more possible. Ref: http://t.co/Hdpknwy5bK #ncistg14
9:15am March 21st 2014 via Hootsuite
Church: Q: Can mtDNA be edited? A: Working on it, looks promising #ncistg14
9:14am March 21st 2014 via Hootsuite
Church: Synthetic epigenomics, with orthogonal Cas9 proteins, many more in the pipeline http://t.co/kipsMv7osP #ncistg14
9:12am March 21st 2014 via Hootsuite
Church: CRISPR can be in the MB range, also between chromosomes #ncistg14
9:10am March 21st 2014 via Hootsuite
