BIOMOLECULAR INTERACTIONS IN HUMAN CELL GROWTH
Regulated interactions between diverse molecules, including DNA, RNA, proteins, and polycations, are essential for human cell survival and neurological function. The long-term goals of our research are to gain an improved understanding of the regulation of biomolecular interactions and enable the development of new approaches to treat disease and affect aging processes.
RESEARCH PROJECTS
1) Non-coding RNA-protein interactions affecting chromatin state
Epigenetic regulation of chromatin controls gene expression patterns in humans and enables cell type specificity. Non-coding RNAs can regulate gene expression by affecting the localization and function of epigenetic modifier proteins on chromatin, and trigger a switch from transcriptionally active (euchromatin) to inactive (heterochromatin) state. Our group is studying how non-coding RNAs specify cell fate decisions. The DUBR non-coding RNA maintains chromatin state during differentiation by controlling chromatin accessibility for AP-1 family transcription factors. Similarly, the X inactive specific transcript (XIST) non-coding RNA controls the function of transcriptional repressors (SHARP/N-CoR) and histone deacetylase (HDAC) proteins to silence an entire X chromosome during human development.
2) Regulatory networks in dynamic neuronal gene expression
Eukaryotic ribonucleoprotein (RNP) complexes such as the spliceosome and the ribosome illustrate critical relationships between proteins and non-coding RNAs in cell function. TDP-43 dysfunction is prevalent in patients suffering from the human neurodegenerative diseases Alzheimer's, LATE, and ALS-FTLD. We found that MALAT1 non-coding RNA regulates TDP-43 binding in RNA networks in the nucleus, and are developing new chemical biology and bioinformatics tools to study and perturb these functional interactions. Our goal is to identify new targets for therapeutic interventions and drug treatments.
3) Uncovering new functions of cancer cell growth associated non-coding RNA transcripts
Recent bioinformatics studies identified a set of cancer-associated non-coding RNAs whose expression is linked to metastasis and decreased long-term patient survival. We use a combination of chemical biology and genomics tools to examine the contributions of cancer-associated ncRNAs to cell growth, with a focus on oxidative stress and DNA damage responses.
Epigenetic regulation of chromatin controls gene expression patterns in humans and enables cell type specificity. Non-coding RNAs can regulate gene expression by affecting the localization and function of epigenetic modifier proteins on chromatin, and trigger a switch from transcriptionally active (euchromatin) to inactive (heterochromatin) state. Our group is studying how non-coding RNAs specify cell fate decisions. The DUBR non-coding RNA maintains chromatin state during differentiation by controlling chromatin accessibility for AP-1 family transcription factors. Similarly, the X inactive specific transcript (XIST) non-coding RNA controls the function of transcriptional repressors (SHARP/N-CoR) and histone deacetylase (HDAC) proteins to silence an entire X chromosome during human development.
2) Regulatory networks in dynamic neuronal gene expression
Eukaryotic ribonucleoprotein (RNP) complexes such as the spliceosome and the ribosome illustrate critical relationships between proteins and non-coding RNAs in cell function. TDP-43 dysfunction is prevalent in patients suffering from the human neurodegenerative diseases Alzheimer's, LATE, and ALS-FTLD. We found that MALAT1 non-coding RNA regulates TDP-43 binding in RNA networks in the nucleus, and are developing new chemical biology and bioinformatics tools to study and perturb these functional interactions. Our goal is to identify new targets for therapeutic interventions and drug treatments.
3) Uncovering new functions of cancer cell growth associated non-coding RNA transcripts
Recent bioinformatics studies identified a set of cancer-associated non-coding RNAs whose expression is linked to metastasis and decreased long-term patient survival. We use a combination of chemical biology and genomics tools to examine the contributions of cancer-associated ncRNAs to cell growth, with a focus on oxidative stress and DNA damage responses.
SUPPORT
We are grateful to the following research sponsors for funding and supporting our work:
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