The present invention provides mammalian retinoblastoma (Rb) protein-interacting zinc finger (RIZ) proteins, nucleic acid molecules encoding the RIZ and antibodies specific for the RIZ. The invention also provides screening assays for identifying an agent that effectively alters the association of a RIZ with a second molecule, which can bind to the RIZ. The invention also provides active fragments of RIZ containing the PR domain, which can regulate transcription. In addition, the invention provides methods for introducing a nucleic acid molecule-encoding a RIZ into a cell and for A-contacting a cell with an effective agent in order to modulate a function of a cell. Such methods are useful, for example, for inducing growth of a cardiac cell or a neuronal cell in a subject and for effecting normal growth control to a tumor cell or causing differentiation of tumor cells. The invention further provides methods for detecting a RIZ in a sample by detecting the RIZ or a nucleic acid molecule encoding the RIZ. Such methods are useful to diagnose a pathology that is characterized by an increased or decreased level of a RIZ in a cell or by expression of a mutant RIZ in a cell.
Pr-Domain Containing Nucleic Acids, Polypeptides, Antibodies And Methods
The invention provides an isolated PR Family Member (PFM) nucleic acid molecule that contains a PFM PR domain nucleotide sequence, a PFM ZF domain nucleotide sequence, or a modification thereof. The invention also provides an isolated PFM nucleic acid molecule that contains a nucleotide sequence that encodes a PFM PR domain polypeptide, or that encodes a PFM ZF domain polypeptide, or that encodes an immunologically equivalent modification thereof. Also provided are isolated PFM oligonucleotides. The invention also provides methods for detecting a PFM nucleic acid molecule in a sample. Further provided is a method of modulating cell growth by expressing an encoded PFM polypeptide in the cell.
Methods Of Detecting And Treating Microsatellite-Instability Positive Tumors Using Riz
Shi Huang - San Diego CA, US Robert B. Chadwick - Castro Valley CA, US
Assignee:
The Burnham Institute - La Jolla CA The Ohio State University - Columbus OH
International Classification:
C07H021/04 C12Q001/68
US Classification:
435 6, 435 911, 435 912, 536 231, 536 243
Abstract:
The invention provides a method of inhibiting growth of a microsatellite instability (MSI)-positive tumor. The method is practiced by introducing into an MSI-positive tumor a nucleic acid molecule encoding a RIZ1 polypeptide and expressing the RIZ1 polypeptide in the tumor in an effective amount to inhibit growth of the tumor. Also provided is a method of determining the MSI status of a tumor. The method is practiced by determining in the tumor the number of adenosine (A) nucleotides in a poly(A) tract of a RIZ nucleic acid molecule in the tumor. An abnormal number of adenosine nucleotides in a RIZ poly(A) tract indicates that the tumor is MSI-positive.
Pr/Set-Domain Containing Nucleic Acids, Polypeptides, Antibodies And Methods Of Use
The present invention provides an isolated nucleic acid molecule encoding a PFM/SET polypeptide. Also provided is an isolated nucleic acid molecule encoding a functional fragment of a PFM/SET polypeptide that contains a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide of the invention. Further provided by the invention are PFM/SET polypeptides, and functional fragments thereof that contain a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide. The invention also provides PFM/SET antibodies, PFM/SET modulatory compounds, and related methods. The molecules of the invention can be used in methods of screening for a compound that modulates PFM/SET polypeptide histone methyltransferase activity and to modulate cell proliferation to prevent or treat proliferative disorders, including cancer. Additionally, the molecules and methods of the invention can be used to diagnose and prognose proliferative disorders.
Screening, Diagnostic And Therapeutic Methods Relating To Riz
The invention provides a method of screening for a compound that modulates RIZ histone methyltransferase (HMT) activity, by contacting a RIZ or RIZ fragment having HMT activity with one or more candidate compounds, and determining histone methyltransferase activity of the contacted RIZ or RIZ fragment. Also provided is a method of screening for a compound that modulates progesterone receptor (PR) activity, by providing a RIZ1 modulatory compound, and determining the ability of the RIZ1 modulatory compound to modulate PR activity. Further provided is a method of identifying an individual with an estrogen receptor positive (ER+) tumor having a reduced likelihood of responding to endocrine therapy. The method involves determining the RIZ1 status of the tumor, wherein an abnormal RIZ1 status identifies the individual as an individual with a reduced likelihood of responding to endocrine therapy.
Pr/Set-Domain Containing Nucleic Acids, Polypeptides, Antibodies And Methods Of Use
The present invention provides an isolated nucleic acid molecule encoding a PFM/SET polypeptide. Also provided is an isolated nucleic acid molecule encoding a functional fragment of a PFM/SET polypeptide that contains a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide of the invention. Further provided by the invention are PFM/SET polypeptides, and functional fragments thereof that contain a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide. The invention also provides PFM/SET antibodies, PFM/SET modulatory compounds, and related methods. The molecules of the invention can be used in methods of screening for a compound that modulates PFM/SET polypeptide histone methyltransferase activity and to modulate cell proliferation to prevent or treat proliferative disorders, including cancer. Additionally, the molecules and methods of the invention can be used to diagnose and prognose proliferative disorders.
Pr-Domain Containing Nucleic Acids, Polypeptides, Antibodies And Methods
The invention provides an isolated PR Family Member (PFM) nucleic acid molecule that contains a PFM PR domain nucleotide sequence, a PFM ZF domain nucleotide sequence, or a modification thereof. The invention also provides an isolated PFM nucleic acid molecule that contains a nucleotide sequence that encodes a PFM PR domain polypeptide, or that encodes a PFM ZF domain polypeptide, or that encodes an immunologically equivalent modification thereof. Also provided are isolated PFM oligonucleotides. The invention also provides methods for detecting a PFM nucleic acid molecule in a sample. Further provided is a method of modulating cell growth by expressing an encoded PFM polypeptide in the cell. Also provided is an isolated PFM polypeptide, containing a PFM PR domain amino acid sequence, or a PFM ZF domain amino acid sequence, or a modification thereof. The invention also provides an isolated PFM peptide, containing at least 8 contiguous amino acids of a PFM polypeptide.
Pr/Set-Domain Containing Nucleic Acids, Polypeptides, Antibodies And Methods Of Use
The present invention provides an isolated nucleic acid molecule encoding a PFM/SET polypeptide. Also provided is an isolated nucleic acid molecule encoding a functional fragment of a PFM/SET polypeptide that contains a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide of the invention. Further provided by the invention are PFM/SET polypeptides, and functional fragments thereof that contain a PR, SET, PRAZ or PKZL domain of a PFM/SET polypeptide. The invention also provides PFM/SET antibodies, PFM/SET modulatory compounds, and related methods. The molecules and methods of the invention can be used to modulate cell proliferation to prevent or treat proliferative disorders, including cancer. Additionally, the molecules and methods of the invention can be used to diagnose and prognose proliferative disorders.
University of California, San Diego - Jacobs School of Engineering
Postdoctoral Scholar
University of California, San Diego
Postdoctoral Scholar
Qingdao Institute of Bioenergy & Bioprocess Technology
Postdoctoral Fellow
Technical University of Denmark Nov 2015 - May 2016
Phd Student
Qingdao Institute of Bioenergy & Bioprocess Technology Aug 2011 - Aug 2012
Researcher
Education:
Qibebt, China Academy of Science 2012 - 2015
Doctorates, Doctor of Philosophy, Molecular Biology, Biochemistry, Philosophy
Shanghai Normal University 2008 - 2011
Masters
University of Chinese Academy of Sciences
Doctorates, Doctor of Philosophy, Philosophy