Over 180 chemical modifications of RNA have been identified, we are asking which of these modifications and to what extent they are found in the different types of RNA in human cells. This project includes finding ways to isolate different species of RNA, sequencing those RNA directly with nanopore-based methods, and in collaboration wit
Over 180 chemical modifications of RNA have been identified, we are asking which of these modifications and to what extent they are found in the different types of RNA in human cells. This project includes finding ways to isolate different species of RNA, sequencing those RNA directly with nanopore-based methods, and in collaboration with colleagues, analyzing the RNA by mass spectrometry. In parallel, we are also developing computational methods to analyze and display the results.
Gene expression determines cell identity and function. Expression levels of genes are influenced by highly regulated steps in RNA synthesis and co- as well as post-transcriptional processing. We are examining how nucleic acid sequences and structures influence RNA polymerase activities. One project is examining the effect of R-loops in
Gene expression determines cell identity and function. Expression levels of genes are influenced by highly regulated steps in RNA synthesis and co- as well as post-transcriptional processing. We are examining how nucleic acid sequences and structures influence RNA polymerase activities. One project is examining the effect of R-loops in pausing transcription elongation. We detail RNA polymerases' activities and assess the co-transcriptional steps that influence gene expression. We use molecular and genetic approaches in gene-specific and genome-wide studies.
ALS4 is a juvenile-onset upper and lower motor neuron disease. It is an autosomal recessive disease caused by mutations in senataxin, an RNA-DNA helicase that resolves R-loops. In collaboration with colleagues at NIH, we are determining the natural history and identifying the molecular basis of ALS4. Additionally, we are studying the f
ALS4 is a juvenile-onset upper and lower motor neuron disease. It is an autosomal recessive disease caused by mutations in senataxin, an RNA-DNA helicase that resolves R-loops. In collaboration with colleagues at NIH, we are determining the natural history and identifying the molecular basis of ALS4. Additionally, we are studying the function of senataxin, and developing RNA-based therapeutics for ALS4.
Alzheimer's Disease affects 7 million Americans and 55 million people worldwide. APOE4 is a major genetic risk factor. Nearly 70% of AD patients have at least one APOE4 allele. Yet current therapies are not designed for APOE4 carriers and may be less effective or cause more side effects in this majority group. We have identified an enh
Alzheimer's Disease affects 7 million Americans and 55 million people worldwide. APOE4 is a major genetic risk factor. Nearly 70% of AD patients have at least one APOE4 allele. Yet current therapies are not designed for APOE4 carriers and may be less effective or cause more side effects in this majority group. We have identified an enhancer RNA, AANCR, that regulates APOE transcription. We are studying APOE biology and developing RNA-based therapeutics to silencer APOE4.
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