Leaders in Pharmaceutical Business Intelligence (LPBI) Group

3:45 – 4:15, 2014, Scott Lowe “Tumor suppressor and tumor maintenance genes”

Reporter: Aviva Lev-Ari, PhD, RN

LIVE from Kresge Auditorium @MIT

Key concepts captured:

• Cancer drivers: Normal to tumor
• Cancer dependenceies: Tumor to Normal
• shRNA – tumor suppressor loss
• the PLATFORM: miR-based shRNAs
• Inducible promoter(TRE, TREtight) miRNA backbone
• Off target effects are concentration dependent (infection transduction
• miR-based shRNA do not disrupt miRNA biogenesis
• Building mouse models with RNAi
• tissue specific gene expression – adoption to the CRISPR Cas9 system
• toxicity – Brd4 is a novel therapeutic target for leukemia
• Impact of Brd4 inhibition in vivo
• Toxicity assay: in 7 weeks edepermal hyperlesia, loss of hair
• immunohistology – abnormal
• Effects of Brd4 inhibition are reversible
• sensitise DNA damage
• toxicity of DNA inhibition
• APC – (Adenomatous polyposis Coli) – colonorectal cancer –>> deregulation
• APC loss triggers promotes aberrant proliferation and differentiation
• stem cells
• Acute effects of APC loss are completely reversible
• mosaic shRNA expression in the gut: Tamoxaphine reduce shRNA
• polyp formation and regression as function of the induction
• APC restoration leads to tumor regression
• APC restoration induces tumor cell differentiation in small intestine
• intestinal crypt formation –.. restoration restores homeostasis
• APC reactivation restores homeostasis
• tumor progression: polyp (removable) to carcinoma (deadly)
• Kras cooperates with shAPC to accelerate disease
• APC restoration promotes invasive tumors dependent on APC loss

3:45 – 4:15, 2014,  Scott Lowe  “Tumor suppressor and tumor maintenance genes”

@MIT – Summer Symposium 2014: RNA Biology, Cancer and Therapeutic Implications, June 13, 2014 8:30AM – 4:30PM, Kresge Auditorium @MIT

http://ki.mit.edu/news/symposium

REALTIME event coverage for the Scientific Media by Dr.  A. Lev-Ari 

in Open Access Scientific Journal of Leaders in Pharmaceutical Business Intelligence (LPBI)

http://pharmaceuticalintelligence.com

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Scott Lowe, PhD 
Associate Director for Basic Cancer Research, Cancer Biology and Genetics Program; Chair, Geoffrey Beene Cancer Research Center,Memorial Sloan-Kettering Cancer Center 
Investigator, Howard Hughes Medical Institute

Scott W. Lowe is a Member of the Cancer Biology and Genetics Program at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City where he serves as the Associate Director for Basic Cancer Research. He is also Chair of the Geoffrey Beene Cancer Research Center and an Investigator for the Howard Hughes Medical Institute. Dr. Lowe received a Bachelor of Science Degree from the University of Wisconsin-Madison where he worked for several years studying the molecular basis of hypercholesterolemia. He performed his graduate studies at the Massachusetts Institute of Technology under the supervision of Dr. H. Earl Ruley, and received his PhD. for research on the role of the p53 tumor suppressor in oncogenic transformation, apoptosis, and chemosensitivity. After a brief postdoctoral position in the MIT Center for Cancer Research with Drs. David Housman and Tyler Jacks, Dr. Lowe initiated independent research at Cold Spring Harbor Laboratory as a Cold Spring Harbor Laboratory Fellow and then as a member of the faculty. Dr. Lowe’s research has made important contributions to our understanding of the p53 tumor suppressor network, as well as the processes of multi-step carcinogenesis, cellular senescence, and tumor-cell drug resistance. Current research is based on the premise that the path of cancer evolution dictates a tumor’s subsequent response to therapy and creates unique vulnerabilities that represent therapeutic opportunities. Hence, the laboratory applies mouse models, RNA interference and cancer genomics in a coordinated effort to identify cancer drivers and dependencies that will be useful therapeutic targets relevant to specific cancer genotypes. Dr. Lowe’s work has been recognized by several awards, including a Sydney Kimmel Foundation Scholar Award, a Rita Allen Foundation Scholar Award, the AACR Outstanding Investigator Award, the Paul Marks Prize for Cancer Research, the Kunio Yagi Medal, and the Alfred G. Knudsen Award. He also has been inducted as a Fellow in the American Academy of Arts and Sciences.