ARRA Investments in Epigenetics
Public Health Burden
Many common diseases in the United States, such as cancer, neurological disorders and cardiovascular disease, are thought to involve epigenetic processes that control the activity of genes, but do not involve changes, such as mutations, to the DNA sequence of the genome.
Our understanding of how epigenetic changes occur and how they may contribute to development of specific diseases is at its infancy. This is partly due to the limited supply of available technologies and tools to characterize the epigenetic features of a cell on a global (genome-wide) scale so as to define the “epigenome” of a cell under normal conditions and during conditions of aging, development, and disease. These tools would enable researchers to identify new molecular signatures and biomarkers of disease initiation, progression, and response to therapeutics.
The following ARRA awards are focused on developing new technologies and tools to accelerate research on the epigenetic contributions to disease and treatment:
Developing new technology for global (genome-wide) analysis of modifications to histone proteins in cells.
Developing new technology for global (genome-wide) analysis of all sites of histone protein interaction in yeast cells.
Defining molecular signatures or profiles of microRNAs that can be used to predict response to chemotherapeutics in animals and humans.
Diagnosis and Treatment
Identifying the contribution of epigenetics to susceptibility and risk of diseases such as cancer, neurological disorders, and cardiovascular disease paves the way for the development of new diagnostics and treatments for these conditions. Studies that seek to identify small molecules that bind to proteins involved in epigenetic processes, such as histones, and affect their ability to control gene activity can be used as “molecular probes” to better understand epigenetic processes in health and disease, and as potential targets for the development of new therapies.
ARRA funded grants that focus on development of new targets for research and drug development include:
Developing a new protein array technology and computational tools for global, high throughput discovery of proteins that bind to histones and affect their ability to control the activity of genes that may be related to cancer.
Conducting high throughout screening to identify small molecules that can bind to proteins involved in modifying histone structure and its ability to regulate gene activity as a tool for probing biological systems and developing new therapeutic targets for cancer.
Conducting high throughput screening to identify small molecules that bind to proteins that are involved in modifying histone structure and its ability to regulate gene activity as a tool for probing biological systems and developing new therapeutic targets for cancer and neurodegenerative disorders.
Conducting high throughput screening to identify small molecules that bind to proteins that are involved in modifying histone structure and its ability to regulate gene activity as a tool for developing new biomarkers of disease and new therapies for neurological disorders and cardiovascular disease.
-- Direct detection of epigenetic modifications in their native chromatin contexts -- Jaffe, Jacob David (MA)
-- Identification of histone modification interaction networks -- Parthun, Mark (OH)
-- The discovery of microRNAs that predict chemotherapeutic responsiveness in cancer -- Tavazoie, Sohail (NY)
-- Applying peptide and protein domain microarrays to epigenetic research -- Gozani, Or P. (CA)
-- Discovery of small molecule MBT domain antagonists -- Frye, Stephen Vernon (NC)
-- Identification of small molecule inhibitors of sumoylation -- Prelich, Gregory (NY)
-- Mechanism-based small molecule epigenetic modulators: targeting specific HDACs -- Chen, Lin (CA)
Page Last Updated on June 30, 2018
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