University of California

The Salk Institute for Biological Studies

Ionis Pharmaceuticals, Inc.

The Population Council, Center for Biomedical Research

Li, Wenbo

Rosenfeld, Michael G.

Michael G Rosenfeld

Ronald Mark Evans

Christopher K Glass

Jean E Rivier

Wylie W Vale, Jr

Sylvia Evans

Ju Chen

David Rose

Chenleng Cai

Bogi Anderson

Wenlai Zhou

Joseph Torchia

Susan M Freier

Gabriel Pascual

Joachim Spiess

Marvin R Brown

C Wayne Bardin

Peter N Schlegel

Richard V Pearse

Bogi Andersen

Wenbo Li

Susan G Amara

Larry Swanson

Kelly E Mayo

Gail Cerelli

Michael T Lam

Disclosed herein are methods and compounds for inhibiting gene expression by inhibiting enhancer RNAs (eRNAs). Such methods and compounds are useful for reducing expression of certain genes, many of which are associated with a variety of diseases and disorders.

Modulation of enhancer RNA mediated gene expression

The present invention relates to a method of screening for a compound that regulate SUMOylation of the nuclear receptor proteins comprising contacting the compound of interest to the nuclear receptor protein, and detecting SUMOylation of the nuclear receptor protein, thereby screening for a compound that regulates SUMOylation.

Identification of an evolutionarily conserved pathway mediating transrepression of inflammatory response genes by nuclear receptors

The invention herein provides a mode of treating a disease associated with the regulation of T-Box and N-Myc gene, which includes cancers and heart disease in human and other subjects by identifying and administering a compound which modulates T-Box or N-Myc function. The invention also provides polynucleotides, polypeptides, vectors, cells, tissues and organisms useful in the identification and treatment of metabolic syndrome. A number of desirable cell proliferation and senescence regulating aspects are achieved by various embodiments of the present invention.

Compositions and methods for treating diseases associated with T-box and N-Myc

The invention herein provides a mode of treating a disease associated with the regulation of T-Box and N-Myc gene which includes cancers and heart disease in human and other subjects by identifying and administering a compound which modulates T-Box or N-Myc function. The invention also provides polynucleotides, polypeptides, vectors, cells, tissues and organisms useful in the identification and treatment of metabolic syndrome. A number of desirable cell proliferation and senescence regulating aspects are achieved by various embodiments of the present invention.

The present invention provides a substantially purified nucleic acid molecule encoding a p/CIP polypeptide, which regulates the activity of CBP/p300-dependent transcription factors. The invention also provides a substantially purified p-CIP polypeptide and active fragments thereof. In addition, the invention provides methods of identifying an effective agent that alters the association of a p/CIP polypeptide with a second protein. Further provided herein are methods of selectively inhibiting signal transduction pathways using an active fragment of a p/CIP polypeptide or a nucleic acid molecule encoding such an acive fragment.

Transcription factor coactivator protein, p/CIP

The present invention provides a substantially purified nucleic acid molecule encoding p/CIP, which regulates the activity of CBP/p300 dependent transcription factors. The invention also provides substantially purified p/CIP and peptide portions of p/CIP. The invention also provides methods of selectively inhibiting signal transduction pathways using a peptide portion of p/CIP or a nucleic acid molecule encoding such a peptide portion.

Disclosed is a POU transcription factor, Sprm-1 and analogs thereof, DNA molecules encoding the Sprm-1 proteins, and chimeric constructs, vectors and host cells containing the DNA molecules. Also disclosed are methods to identify putative male contraceptive agents. One involves the steps of isolating a DNA regulatory region responsive to Sprm-1, stably transforming a heterologous cell line with a first chimeric DNA construct containing a constitutive promoter capable of functioning in the cell line operably linked to a Sprm-1 DNA and a second chimeric DNA construct containing the DNA regulatory region operably linked to a reporter gene. The thus-transformed cell line is cultural in media containing the compound so that the thus-cultured cell line can be assayed to determine the Sprm-1 inhibitory activity of the compound. The above method can be modified to evaluate the Sprm-1 inhibitory activity of DNA molecules of interest, by transiently transfecting the thus-transformed cell line with a third DNA construct containing a constitutive promoter capable of functioning in the cell line operably linked to the DNA molecule, and then culturing the thus-transfected cell line so that it can be assayed to determine the inhibitory activity of the DNA molecule. Antibodies specific to Sprm-1, and their use in diagnosing male germ cell Sprm-1-mediated diseases or conditions are further disclosed.

Isolated DNA molecule encoding SPRM-1 protein

A gene encoding for alternative forms of a POU domain transcription factor is disclosed. The first polypeptide form of the transcription factor includes a transferable region which inhibits DNA binding by itself and other transcription factors. The second polypeptide form serves to activate expression of a gene typical for terminal differentiation of skin. Fusion proteins wherein the inhibitory region of the first form of the gene is coupled to, and inhibits the function of, other transcription factors are also disclosed.

Transcription factor for regulation of the development of skin and hair

Proteins with inhibin activity having a weight of about 32,000 daltons. The molecule is composed of two chains having molecular weights of about 18,000 and about 14,000 daltons, respectively, which are bound together by disulfide bonding. The 18K chain is obtained from the human inhibin gene and has the formula: H-Ser-Thr-Pro-Leu-Met-Ser-Trp-Pro-Trp-Ser-Pro-Ser-Ala-Leu-Arg-Leu-Leu-Gln- Arg-Pro-Pro-Glu-Glu-Pro-Ala-Ala-His-Ala-Asn-Cys-His-Arg-Val-Ala-Leu-Asn-Ile -Ser-Phe-Gln-Glu-Leu-Gly-Trp-Glu-Arg-Trp-Ile-Val-Tyr-Pro-Pro-Ser-Phe-R.sub. 65 -Phe-His-Tyr-Cys-His-Gly-Gly-Cys-Gly-Leu-His-Ile-Pro-Pro-Asn-Leu-Ser-Leu-P ro-Val-Pro-Gly-Ala-Pro-Pro-Thr-Pro-Ala-Gln-Pro-Tyr-Ser-Leu-Leu-Pro-Gly-Ala- Gln-Pro-Cys-Cys-Ala-Ala-Leu-Pro-Gly-Thr-Met-Arg-Pro-Leu-His-Val-Arg-Thr-Thr -Ser-Asp-Gly-Gly-Tyr-Ser-P e-Lys-Tyr-Glu-Thr-Val-Pro-Asn-Leu-Leu-Thr-Gln-His-Cys-Ala-Cys-Ile-OH, wherein R.sub.65 is Ile or Arg. The 18K chain is connected by disulfide bonding to the 14K chain.

Human inhibin

Human CGRP (calcitonin-gene-related peptide) has the formula: H-Ala-Cys-Asn-Thr-Ala-Thr-Cys-Val-Thr-His-Arg-Leu-Ala-Gly-Leu-Leu-Ser-Arg- Ser-Gly-Gly-Val-Val-Lys-Asn-Asn-Phe-Val-Pro-Thr-Asn-Val-Gly-Ser-Lys-Ala-Phe -NH.sub.2. Human CGRP or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals, including humans, to influence memory, mood and pain appreciation and to achieve a substantial lowering of blood pressure or gastric acid secretion over an extended period of time. They also may be administered to affect ingestion behavior, taste and sensory perception. By using human CGRP to generate production of antibodies, it should be possible to diagnose human medullary thyroid carcinoma via immunoassay techniques.

DNA encoding human CGRP

Human CGRP

CGRP (calcitonin-gene-related peptide) has the formula: ##STR1## A related peptide has the residue Lys instead of Glu in the 35-position. CGRP or this homolog or pharmaceutically acceptable salts thereof, dispersed in a pharmaceutically acceptable liquid or solid carrier, can be administered to mammals, including humans, to influence memory, mood and pain appreciation and to achieve a substantial lowering of blood pressure or gastric acid secretion over an extended period of time. They also may be administered to affect ingestion behavior, taste and sensory perception.

Growing community of inventors

San Diego, CA, United States of America

Michael G Rosenfeld