The General Hospital Corporation

Children's Medical Center Corporation

Raul Mostoslavsky

Anders M Naar

Sita Kugel

Frederick W Alt

Hwei-Ling Cheng

David B Lombard

Katrin F Chua

It has been discovered that NAD-dependent histone deacetylase SIRT6 is critical for suppression of PDAC by controlling the expression of Lin28b, which is a negative regulator of let-7 microRNA. Specifically, SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This invention relates generally to agents and methods of reducing expression or activity of Lin28b to treat (aggressive) PDAC in a subject.

Agents and methods for treating pancreatic ductal adenocarcinomas

It has been discovered that NAD+-dependent histone deacetylase SIRT6 is critical for suppression of PDAC by controlling the expression of Lin28b, which is a negative regulator of let-7 microRNA. Specifically, SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This invention relates generally to agents and methods of reducing expression or activity of Lin28b to treat (aggressive) PDAC in a subject.

The present invention is directed to methods for enhancing the replicative capacity of cells, by culturing the cells in the presence of an active agent or compound which inhibits SIRT1. One method provides expanding stem cells by culturing the cells in the presence of a SIRT1 inhibitor. The resulting cultured cells can be used for a variety of applications including cell-based therapies such as bone marrow transplants, gene therapies, tissue engineering, and in vitro organogenesis.

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Boston, MA, United States of America

Raul Mostoslavsky