Botstein: There is a broad consensus that cancer is somatic gain of special properties, and then just natural selection. #AACR14
8:41pm April 5th 2014 via Hootsuite
Botstein: "Evolution is anymore no longer a theory as gravity is." Theoretical and practical reality. #AACR14
8:40pm April 5th 2014 via Hootsuite
Botstein: "It was natural to apply microarray technology to cancer" "Unless you have a primary text, there's nothing to translate" #AACR14
8:38pm April 5th 2014 via Hootsuite
Botstein: 'I don't think of myself (nor any of you thought of me) as a cancer biologist' #AACR14
8:36pm April 5th 2014 via Hootsuite
Tenth Annual AACR-Irving Weinstein Foundation Distinguished Lecture: David Botstein, Princeton Univ "Evolution and Cancer" #AACR14
8:35pm April 5th 2014 via Hootsuite
Solyom: 28/58 in pre-cancerous colon polyps, 13/24 in IBD dysplasias, not found in healthy tissue #AACR14
7:58pm April 5th 2014 via Hootsuite
Solyom: Validated via PCR in somatic L1 insertions in colon ca. Insertions were in many important genes (COSMIC) #AACR14
7:56pm April 5th 2014 via Hootsuite
Solyom: L1-Seq - looking at human-specific L1's via assymetric then hemi-specific PCR PubMed http://t.co/dgPn2I5QT2 #AACR14
7:48pm April 5th 2014 via Hootsuite
Solyom: Has unique gastrointestinal cancer cancer samples from L1 retroposon insertions. Also IBD, pancreatic cancers #AACR14
7:46pm April 5th 2014 via Hootsuite
Solyom: >100 diseases caused by retroelement insertions in humans. 25 L1, 61 Alu, 10 SVA... #AACR14
7:43pm April 5th 2014 via Hootsuite
Solyom: Laid out L1 method of transposition Beck Ann Rev Genetics PubMed: http://t.co/lurpKGWW4V #AACR14
7:42pm April 5th 2014 via Hootsuite
Solyom: Concentrating on L1: 6kb, 2 ORF's, 5' and 3' UTR's, 500K copies in human genome. Binds to same RNA that encode it #AACR14
7:40pm April 5th 2014 via Hootsuite
Solyom: Types of mobile elements: L1, Alu, SVA, HERV, DNA transposons. Copy numbers from 2.7K (SVA) to 1M (Alu). #AACR14
7:39pm April 5th 2014 via Hootsuite
Next up: Szilvia Solyom, Johns Hopkins "A potential role of retrotransposons in cancer" #AACR14
7:37pm April 5th 2014 via Hootsuite
Rosenfeld: Pit1 R27W mutation - no catenin binds, combined pituitary hormone deficiency, may become a target #AACR14
7:35pm April 5th 2014 via Hootsuite
Rosenfeld: Knock out wt Pit!, rescue using something called the SAF domain. Enhancers of Pit1 + catenin with matrin3n-network #AACR14
7:34pm April 5th 2014 via Hootsuite
Rosenfeld: Looking at Satb1, b-catenin enhancing transcription of Pit1, and its relation to matrin3 #AACR14
7:32pm April 5th 2014 via Hootsuite
Hearing G. Rosenfeld at #AACR14 reminds me how many super-bright people are working on transcription-factor regulation. True years ago &
7:31pm April 5th 2014 via Hootsuite
Rosenfeld: Nuclear architecture: "Fun to watch over the next few years". #AACR14
7:29pm April 5th 2014 via Hootsuite
Rosenfeld: Super enhancer concept: 212 / 821 not; but the eRNA level not particularly higher. #AACR14
7:27pm April 5th 2014 via Hootsuite
Rosenfeld: Same as with RAR, GATA3 is required. Sequential ChIP analysis shows co-recruitment of MegaTrans complex to enhancers #AACR14
7:26pm April 5th 2014 via Hootsuite
Rosenfeld: Mass-spec analysis of IP pulldown of RAR alpha: 2nd, GATA3 is recruited in trans to ER fn enhancer #AACR14
7:24pm April 5th 2014 via Hootsuite
Rosenfeld: Every enh (1000+) with ER, had RARalpha and RARgamma. Looking at in trans - protein-protein interaction #AACR14
7:23pm April 5th 2014 via Hootsuite
Rosenfeld: ER binds, brings in a complex (GATA3, c-Jun, c-Fos, many others); FOXA1 also the 'pioneer' #AACR14
7:22pm April 5th 2014 via Hootsuite
Rosenfeld: MegaTrans complex - present on active enhancers, not inactive ones #AACR14
7:21pm April 5th 2014 via Hootsuite
Rosenfeld: Knock down condensins - lower ER-regulated enhancers. How does it work? Other factors (HECTD1) recruited too #AACR14
7:20pm April 5th 2014 via Hootsuite
Rosenfeld: Looking at estrogen receptor and recruitment of condensins to enhancers #AACR14
7:19pm April 5th 2014 via Hootsuite
Rosenfeld:GRO-Seq and enhancer RNA; knocked-down eRNA req'd for both enhancer and coding gene transcription #AACR14
7:17pm April 5th 2014 via Hootsuite
Rosenfeld: H4R3me2(s) mark: a repressive mark, read by 7SK methylated xcript; JMJD6 disarms repression; pause released #AACR14
7:16pm April 5th 2014 via Hootsuite
Rosenfeld: Another type of enhancer, an 'anti-pause enhancer'. 1K identified Cell 2013 PubMed: http://t.co/djC2v1hZvK #AACR14
7:14pm April 5th 2014 via Hootsuite
Rosenfeld: But it appears that in stem cells - the enhancers are pre-marked to preclude premature enhancer:promoter looping #AACR14
7:13pm April 5th 2014 via Hootsuite
Rosenfeld: Are enhancers functional? Idea is that they are 'born' when several xf bind, signalling, ncRNA, H3K4me1 activate promoter #AACR14
7:12pm April 5th 2014 via Hootsuite
Rosenfeld: Enhancers we know little about. They are themselves transcription units. (Using GRO-seq in br ca cells) #AACR14
7:11pm April 5th 2014 via Hootsuite
Rosenfeld: Number of non-coding RNAs - many-fold greater than coding genes. >35K cis-acting; 6K trans. #AACR14
7:10pm April 5th 2014 via Hootsuite
Next up: M Geoff Rosenfeld, UCSD "Enhancer codes and eRNAs in regulation of gene transcriptional programs" #AACR14
7:09pm April 5th 2014 via Hootsuite
Slack:Q: 34 / let7 are families - look at other forms? A: 15 let-7's, at least 3 miR-34's. Let-7b and 34a for this study. #AACR14
7:08pm April 5th 2014 via Hootsuite
Slack:Q:Look at plasma miRNA? A: Didn't do that in this study #AACR14
7:07pm April 5th 2014 via Hootsuite
Slack: Result: a 44% survival benefit in their mouse model. Points to a post-doct talk tomorrow OASIS sched: http://t.co/PRaGogrRoK #AACR14
7:06pm April 5th 2014 via Hootsuite
Slack: Collaborator let them used an amphoteric liposome called a 'smarticle' to test. 7wk; showed miR-34 elevation in lung + blood #AACR14
7:02pm April 5th 2014 via Hootsuite
Slack: Both miR-34a and let-7b in combination - cell lines suggest synergistic effect for proliferation #AACR14
6:59pm April 5th 2014 via Hootsuite
Slack: Pre-treated with miR-34 - suppressed tumorigenesis. At 10 wk, then miR-34 introduced: tumors failed to progress #AACR14
6:57pm April 5th 2014 via Hootsuite
Slack: Looking at mice miRNA expression, all reduced levels in the mouse model. PubMed: http://t.co/HakgOcinmR #AACR14
6:56pm April 5th 2014 via Hootsuite
Slack: Uses a highly aggressive mouse model (Kras/G12D/+; p53fR172H/+). Poor responder model #AACR14
6:54pm April 5th 2014 via Hootsuite
Slack: let-7, miR-34: repress major oncogenes in lung cancer (RAS, MYC, BCL-2, EGFR); tumor suppressors (p53, RB, p53) [5-50%] #AACR14
6:53pm April 5th 2014 via Hootsuite
Slack: Targeting miRNAs via antisense one approach; another to target miRNA compl. site variants in 3' UTR's http://t.co/SLMpJgPoRy #AACR14
6:50pm April 5th 2014 via Hootsuite
Slack: Croce's data from Volinia et al PNAS 2006 PubMed: http://t.co/5W0crJdFui #AACR14
6:48pm April 5th 2014 via Hootsuite
Slack: Other history: 2002 miR-15/16 first ID'd as involved in carcinogenesis #AACR14
6:47pm April 5th 2014 via Hootsuite
Slack: Collaborating with Mirna Therapeutics. Another timeline 1993 lin-4, 2000 let-7 in human, 2013 first mimics being tested #AACR14
6:46pm April 5th 2014 via Hootsuite
Next up: Frank John Slack, Yale Univ "MicroRNA-based therapeutics in cancer" #AACR14
6:45pm April 5th 2014 via Hootsuite
He:Q: How a polycistronic RNA have different levels of exp? A: Differential processing by Drosha; also microRNA stability #AACR14
