University of Massachusetts

Jack L Leonard

Karl J Simin

Deborah M Leonard

Peter E Newburger

Alan P Farwell

The invention relates to novel therapeutic approaches to cancer treatment that exploits tumor suppressor functions of DKK3b by site-specific delivery of DKK3b. Novel therapeutics and methods for treating tumors and cancers utilizing DKK3b tumor suppressor functions are disclosed.

Anti-tumor properties of Dickkopf 3b

The invention relates to the discovery of a vital new component of the Wnt pathway that regulates trafficking of &#x3b2;-catenin to the cell nucleus and novel therapeutic approaches to cancer treatment. Disclosed herein is a previously unknown, essential component of the Wnt/&#x3b2;-catenin signaling pathway that governs the quantity of &#x3b2;-catenin delivered to the cell nucleus. This intracellular inhibitor of &#x3b2;-catenin signaling (IBS) is transcribed from a second transcriptional start site adjacent to exon 3 of the Dkk3 gene and is required for early mouse development. IBS captures &#x3b2;-catenin destined for the nucleus in a complex with &#x3b2;-TrCP that is bound to the actin cytoskeleton and unavailable for nuclear translocation.

Anti-cancer and anti-inflammatory therapeutics and methods thereof

Truncated thyroid hormone receptors &#x394;TR&#x3b1;1 and &#x394;TR&#x3b1;2 have been discovered to play a role in actin-based endocytosis, e.g., in the nervous system. The invention relates to methods of discovering ligands effective in modulating endocytosis and transgenic mice with altered expression of &#x394;TR&#x3b1;1 and &#x394;TR&#x3b1;2. The invention is useful for the discovery and testing of compounds for treating disorders of the nervous system such as depression.

Methods for identifying compounds that modulate &#x394;TR&#x3b1;2 activity

Truncated thyroid hormone receptors &Dgr;TR&agr;1 and &Dgr;TR&agr;2 have been discovered to play a role in actin-based endocytosis, e.g., in the nervous system. The invention relates to methods of discovering ligands effective in modulating endocytosis and transgenic mice with altered expression of &Dgr;TR&agr;1 and &Dgr;TR&agr;2. The invention is useful for the discovery and testing of compounds for treating disorders of the nervous system such as depression.

Non-nuclear effects of thyroid hormone

Methods of controlling the in vivo and in vitro expression of a heterologous protein by transfecting a cell with a first nucleic acid encoding the heterologous polypeptide, wherein at least one codon of mRNA transcribed from the first nucleic acid is replaced by the codon UGA, and a second nucleic acid operably linked to the first nucleic acid, the second nucleic acid directing the translation of the UGA codon as selenocysteine only when the cell can obtain selenium from the medium in which it is grown; and growing the cell under conditions in which the production of the polypeptide is controlled by the level of selenium available to the cell.

Post transcriptional gene regulation by selenium

The invention provides methods for determining the structure of a polypeptide by a) transfecting a cell with (i) a first nucleic acid encoding the polypeptide, wherein at least one, specific codon of mRNA transcribed from the first nucleic acid is replaced by the codon UGA, and (ii) a second nucleic acid, operably linked to the first nucleic acid, that directs the translation of the UGA codon as selenocysteine only when the cell can obtain selenium from the medium in which it is grown; b) growing the cell in selenium-containing growth medium under conditions in which the cell incorporates at least one selenocysteine residue into the polypeptide at a specific location; c) isolating the polypeptide from the cell or the growth medium; d) forming a crystal of the polypeptide; and e) performing X-ray crystallography on the crystal, wherein the selenocysteine residue is used to determine the structure of the polypeptide.

Growing community of inventors

Shrewsbury, MA, United States of America

Jack L Leonard