Bruce M Spiegelman

US Patent:

6426411, Jul 30, 2002

Filed:

Dec 1, 1998

Appl. No.:

09/203453

Inventors:

Bruce M. Spiegelman - Waban MA
Pere Puigserver - Brookline MA
Zhidan Wu - Boston MA
Guillaume Adelmant - Boston MA

Assignee:

Dana-Farber Cancer Institute - Boston MA

International Classification:

C07H 2104

US Classification:

536 235, 536 234, 435 691, 4352523

Abstract:

The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e. g. , brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

US Patent:

6475778, Nov 5, 2002

Filed:

Feb 13, 1998

Appl. No.:

09/023905

Inventors:

Thomas M. Roberts - Cambridge MA
Frederick J. King - Brookline MA
David F. Harris - Gales Ferry CT
Erding Hu - King of Prussia PA
Bruce Spiegelman - Waban MA
Joanne Chan - Brookline MA

Assignee:

Dana-Farber Cancer Institute - Boston MA

International Classification:

C12N 1500

US Classification:

4353201, 435 691, 435325, 435455, 536 231, 536 235

Abstract:

The present invention relates to novel SH3 domain binding protein, referred to herein a DEF polypeptides. The DEF polypeptides comprise several motifs including a src SH3 consensus binding sequence, four ankyrin repeats, one zinc finger domain and six copies of a proline-rich tandem repeat. DEF polypeptides may function as mediators of SH3 domain-dependent signal transduction pathways and, thus may mediate multiple signaling events such as cellular gene expression, cytoskeletal architecture, protein trafficking and endocytosis, cell adhesion, migration, proliferation and differentiation. Described herein are isolated and antisense nucleic acids molecules, recombinant expression vectors, host cells and non-human transgenic animals containing an insertion or a disruption of the DEF gene. Diagnostic, screening and therapeutic methods utilizing the compositions of the invention are also provided.

US Patent:

6525178, Feb 25, 2003

Filed:

Jul 5, 2001

Appl. No.:

09/900236

Inventors:

Bruce M. Spiegelman - Waban MA
Pere Puigserver - Brookline MA
Zhidan Wu - Boston MA
Guillaume Adelmant - Boston MA

Assignee:

Dana-Farber Cancer Institute - Boston MA

International Classification:

A61K 3800

US Classification:

530350, 530324, 530326, 530328

Abstract:

The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e. g. , brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

US Patent:

6552055, Apr 22, 2003

Filed:

Sep 4, 1997

Appl. No.:

08/923346

Inventors:

Bruce M. Spiegelman - Waban MA
Elisabetta Mueller - Boston MA
Pasha Sarraf - Boston MA
Soner Altiok - Boston MA
Peter Tontonoz - San Diego CA
Samuel Singer - Brookline MA

Assignee:

Dana-Farber Cancer Institute - Boston MA

International Classification:

A61K 3144

US Classification:

514369

Abstract:

The present invention is based on the finding that activation of PPAR plays a key role in inducing growth arrest and differentiation of certain actively proliferating cells. We show that administration of PPAR agonists, such as thiazolidinedione ligands (TZDs), is effective both in vitro and in vivo at inhibiting the proiferation of such cells.

US Patent:

6586455, Jul 1, 2003

Filed:

Feb 1, 2000

Appl. No.:

09/331534

Inventors:

Ronald M. Evans - La Jolla CA
Peter Tontonoz - Los Angeles CA
Bruce M. Spiegelman - Waban MA
Barry M. Forman - Newport Beach CA

Assignee:

The Salk Institute for Biological Studies - La Jolla CA

International Classification:

A61K 314406

US Classification:

514369, 514356, 514569, 424464

Abstract:

In accordance with the present invention, it has been discovered that PPAR is expressed consistently in each of the major histologic types of human liposarcoma. It has further been discovered that maximal activation of PPAR with exogenous ligand (a thiazolidinedione or derivative thereof) promotes terminal differentiation of primary human liposarcoma cells. It has still further been discovered that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR/RXR heterodimer, and that simultaneous treatment of liposarcoma cells with a thiazolidinedionyl moiety (a PPAR-selective class of compounds) and an RXR-specific ligand results in an additive stimulation of differentiation. Accordingly, according to the invention, there have been identified compositions which are useful for the treatment of liposarcomas.

US Patent:

6872391, Mar 29, 2005

Filed:

Sep 27, 2002

Appl. No.:

10/256889

Inventors:

Bruce M. Spiegelman - Waban MA, US
Pere Puigserver - Brookline MA, US
Zhidan Wu - Boston MA, US
Guillaume Adelmant - Boston MA, US

Assignee:

Dana-Farber Cancer Institute - Boston MA

International Classification:

A61K039/395

US Classification:

4241301, 435 71, 435 911, 435326, 435810, 5303881, 530403, 436501, 536 231

Abstract:

The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e. g. , brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

US Patent:

6908987, Jun 21, 2005

Filed:

May 16, 2003

Appl. No.:

10/439799

Inventors:

Bruce M. Spiegelman - Waban MA, US
Pere Puigserver - Brookline MA, US
Zhidan Wu - Boston MA, US
Guillaume Adelmant - Boston MA, US

Assignee:

Dana-Farber Cancer Institute, Inc. - Boston MA

International Classification:

A61K038/00

US Classification:

530350, 530324, 530326, 530328

Abstract:

The invention provides isolated nucleic acids molecules, designated PGC-1 nucleic acid molecules, which encode proteins which can modulate various adipocyte-associated activities including, for example, thermogenesis in adipocytes, e. g. , brown adipocytes, and adipogenesis. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PGC-1 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PGC-1 gene has been introduced or disrupted. The invention still further provides isolated PGC-1 proteins, fusion proteins, antigenic peptides and anti-PGC-1 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.

US Patent:

6974671, Dec 13, 2005

Filed:

Sep 11, 2002

Appl. No.:

10/244045

Inventors:

Marc R. Montminy - San Diego CA, US
Bruce M. Spiegelman - Waban MA, US
Stephan Herzig - Del Mar CA, US

Assignee:

Salk Institute for Biological Studies - La Jolla CA

International Classification:

C12Q001/68
G01N033/00
C07H019/00
C07H021/00
C07H021/02

US Classification:

435 6, 435 94, 435325, 435455, 536 231, 536 235, 536 241, 514 44, 424 931, 800 21, 204450

Abstract:

In accordance with the present invention, it has been discovered that CREB regulates hepatic gluconeogenesis via the co-activator, PGC-1. PGC-1 potentiated glucocorticoid induction of the gene for PEPCK, the rate limiting enzyme in gluconeogenesis, via the glucocorticoid response unit in the promoter, indicating that activation of PGC-1 by CREB in liver contributes to the pathogenesis of diabetes mellitus. In accordance with the above discoveries, the present invention provides a method of identifying a compound that modulates gluconeogenesis. The invention method comprises contacting CREB and a nucleic acid comprising a PGC-1 promoter with a test compound, and determining if the test compound modulates binding between CREB and the PGC-1 promoter.