Scott Douglas Lowe

US Patent:

6555330, Apr 29, 2003

Filed:

Mar 19, 1999

Appl. No.:

09/273220

Inventors:

Howard O. Fearnhead - Huntington Station NY
Mila Elena McCurrach - Cold Spring Harbor NY
Scott William Lowe - Cold Spring Harbor NY
Yuri Lazebnik - East Norwich CT

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

C12Q 102

US Classification:

435 29, 435 71, 435375, 435 681, 435194, 514 12, 514492, 4242771, 530350

Abstract:

The present invention relates to a method of identifying a compound (agent) which modulates apoptosis in transformed cells. In one embodiment, the invention is a method of identifying a compound which selectively activates apoptosis in transformed cells. In an alternative embodiment, the present invention can be used as a method of identifying a compound which inhibits apoptosis in cells. The invention also relates to a method of selectively killing transformed cells, wherein the transformed cell is contacted with a compound which selectively activates apoptosis in transformed cells, as described herein. The invention also relates to methods of treating diseases associated with defective apoptotic machinery (e. g. , cancer, neurodegenerative disease). The methods of the present invention are useful for defining the biochemical mechanisms of apoptosis.

US Patent:

6583333, Jun 24, 2003

Filed:

May 12, 1998

Appl. No.:

09/076776

Inventors:

Scott W. Lowe - Cold Spring Harbor NY
Rachel R. Wallace-Brodeur - Huntington Station NY

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

G01N 3300

US Classification:

800 3, 800 13, 800 14, 800 18, 435325, 435352, 435354, 435355, 424 91, 424 92

Abstract:

A mouse expressing myc in B cells, because of defective function of one or more tumor suppressor genes, is useful for the testing of anti-lymphoma agents and for the testing of genes which may have an effect on the apoptotic pathway. Preferred embodiments include mice of genotypes E-myc/p53 , E-myc/Rb and E-myc/p16 , and cells derived from lymphomas arising in these mice, wherein the cells may have undergone further genetic alteration. Mouse strains, lymphoma cells and cell lines of the invention can be used in methods to discover new anti-lymphoma agents, methods to characterize tumors, and to characterize genes which may affect the development of resistance to anti-tumor agents. Such methods are also part of the invention.

US Patent:

6670139, Dec 30, 2003

Filed:

Jan 22, 1999

Appl. No.:

09/235738

Inventors:

Howard O. Fearnhead - Huntington Station NY
Mila Elena McCurrach - Cold Spring Harbor NY
Scott William Lowe - Cold Spring Harbor NY
Yuri Lazebnik - East Norwich CT

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

G01N 33574

US Classification:

435 721, 435 4, 435 71, 435 723, 435325, 435352, 435354, 435 29, 435194, 435357, 435366, 435367, 435375, 514 12, 514492, 4242771, 530350, 436 63, 436 64, 436 86

Abstract:

The present invention relates to a method of identifying a compound (agent) which modulates apoptosis in transformed cells. In one embodiment, the invention is a method of identifying a compound which selectively activates apoptosis in transformed cells. In an alternative embodiment, the present invention can be used as a method of identifying a compound which inhibits apoptosis in cells. The invention also relates to a method of selectively killing transformed cells, wherein the transformed cell is contacted with a compound which selectively activates apoptosis in transformed cells, as described herein. The invention also relates to methods of treating diseases associated with defective apoptotic machinery (e. g. , cancer, neurodegenerative disease). The methods of the present invention are useful for defining the biochemical mechanisms of apoptosis.

US Patent:

7794941, Sep 14, 2010

Filed:

Aug 13, 2007

Appl. No.:

11/893086

Inventors:

Scott Powers - Cold Spring Harbor NY, US
Lars Zender - Cold Spring Harbor NY, US
Rebecca A. Kohnz - Cold Spring Harbor NY, US
Scott W. Lowe - Cold Spring Harbor NY, US

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

C12Q 1/68
C12P 19/34

US Classification:

435 6, 435 912

Abstract:

The invention provides methods for diagnosing cancers in humans by detecting DNA amplifications in chromosomal region 8p22, which encompasses the FGF-20 gene and the EFHA2 gene. Also provided are cancer treatment methods using inhibitors of FGF-20 and EFHA2. The invention also provides methods for promoting successful regeneration of liver function. These methods can be used therapeutically to improve liver function following transplantation in both recipient and donor subjects.

US Patent:

8137907, Mar 20, 2012

Filed:

Feb 21, 2008

Appl. No.:

12/072115

Inventors:

Lars Zender - Hannover, DE
Scott W. Lowe - Cold Spring Harbor NY, US
Mona S. Spector - Cold Spring Harbor NY, US

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

C12Q 1/68
C07H 21/04
C07K 16/00
C12P 19/34

US Classification:

435 6, 536 231, 536 2431, 536 2433, 5303871, 435 912

Abstract:

This invention provides a genetically tractable in situ non-human animal model for hepatocellular carcinoma. The model is useful, inter alia, in understanding the molecular mechanisms of liver cancer, in understanding the genetic alterations that lead to chemoresistance or poor prognosis, and in identifying and evaluating new therapies against hepatocellular carcinomas. The liver cancer model of this invention is made by altering hepatocytes to increase oncogene expression, to reduce tumor suppressor gene expression or both and by transplanting the resulting hepatocytes into a recipient non-human animal. This invention also relates to the use of RNA interference (RNAi) technology in vivo to efficiently identify genes associated with liver cancer, in particular those encoding tumor suppressors, by knocking out candidate genes using RNAi and observing whether tumors would develop.

US Patent:

8426675, Apr 23, 2013

Filed:

Jun 7, 2011

Appl. No.:

13/155087

Inventors:

Ross Dickins - Carlton, AU
Scott W. Lowe - Cold Spring Harbor NY, US
Gregory J. Hannon - Huntington NY, US

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

A01K 67/00
C07H 21/04

US Classification:

800 14, 536 241, 536 245, 536 232

Abstract:

The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene. In certain embodiments, the invention relates to the use of Tet (tetracycline)-responsive RNA Polymerase II (Pol II) promoters (e. g. , TetON or TetOFF) to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals (e. g. , mice) expressing inducible (such as tetracycline-regulated), reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.

US Patent:

7993925, Aug 9, 2011

Filed:

Jun 5, 2008

Appl. No.:

12/156957

Inventors:

Ross Dickins - Carlton, AU
Scott W. Lowe - Cold Spring Harbor NY, US
Gregory J. Hannon - Huntington NY, US

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

C12N 15/00
C12N 15/86
C12N 15/88
C07H 21/04

US Classification:

435455, 435456, 435457, 435458, 536 245, 800 21, 800 23

Abstract:

The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene. In certain embodiments, the invention relates to the use of Tet (tetracycline)-responsive RNA Polymerase II (Pol II) promoters (e. g. , TetON or TetOFF) to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals (e. g. , mice) expressing inducible (such as tetracycline-regulated), reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.

US Patent:

20040048821, Mar 11, 2004

Filed:

Mar 26, 2003

Appl. No.:

10/401116

Inventors:

Scott Lowe - Cold Spring Harbor NY, US

Assignee:

Cold Spring Harbor Laboratory - Cold Spring Harbor NY

International Classification:

A61K048/00
C07K014/705
C07H021/04

US Classification:

514/044000, 536/023200, 530/350000

Abstract:

Described herein are mutant forms of the adenovirus E1A oncoprotein which are unable to bind and inactivate retinoblastoma (Rb) protein and are defective in promoting apoptosis and chemosensitivity in normal (non-tumorigenic or nonmalignant) cells, but enhance apoptosis and sensitivity to toxic agents (e.g., chemotherapeutic agents, radiation) in Rb protein deficient mutant cells. Such E1A mutant oncoproteins are useful to enhance apoptosis and sensitivity to toxic agents in Rb protein deficient mammalian cells. Also described are agents, useful to promote apoptosis and chemosensitivity in Rb deficient cells, which mimic the activity of an E1A region involved in binding p300 and CBP proteins. Such E1A mimics are, for example, polypeptides which consist essentially of the amino acid residues of such an E1A region (e.g., the N-terminal region, CR1), DNA encoding the E1A region or small organic molecules which mimic the activity of the E1A region. The E1A region mimics are also the subject of the present invention, as are a method of enhancing apoptosis and sensitivity to chemotherapeutic agents and radiation in Rb deficient cells using the E1A mutants and/or mimics, a method of enhancing apoptosis and chemosensitivity and sensitivity to radiation in Rb deficient cells (e.g., tumor or malignant cells) in an individual who is being treated with chemotherapeutic agents and/or radiation using the E1A mutants and/or mimics, a method of identifying an E1A mutant and a method of identifying a molecule which mimics the function of an E1A mutant as described herein.