DETERMINING FUNCTIONS OF LONG NON-CODING RNA AND PROTEIN INTERACTIONS
DNA gets transcribed to RNA which then gets translated into protein. However, not all RNAs are translated, these are called non-coding RNAs (ncRNAs). Long ncRNAs are greater than 200 nucleotides in length, are transcribed by RNA polymerase II, spliced, 5′ capped, and polyadenylated. LncRNAs have been found to be highly important in both pre-transcriptional and post-transcriptional processes. In addition, the location and the structure of lncRNAs can serve as indicators of their important functions. These functions include but are not limited to lncRNAs being associated with transcriptional activation, chromatin remodeling (guides, decoys), sponging, and scaffolding.
Our lab is highly interested in using and optimizing advanced technologies to 1) determine what the specific functions of lncRNAs are, 2) decipher how lncRNAs location in cells determined their function, and 3) how lncRNAs structure affects various cellular processes.
CANCER ASSOCIATED LONG NON-CODING RNAS AND RNA MODIFICATIONS
Long Non-coding RNAs in Late-stage Relapse Breast Cancer
Despite the proven benefits of adjuvant endocrine therapy in women with estrogen receptor (ER) positive BC, relapses still occur even after initial treatment with endocrine therapy for 5 years, referred to as late-stage relapse. To address this, we have identified differentially expressed lncRNAs when comparing primary and late-stage breast cancer patient tumors and primary cell lines by RNA Sequencing. We are now focused on characterizing late-stage relapse BC lncRNAs that are associated with proliferation and metastasis to determine if they may be used as biomarkers and play important roles in late-stage relapse.
Multiple Myeloma (MM) associated long non-coding RNAs and m6A modifications
Multiple myeloma is the second most common hematological malignancy of plasma cells (PCs). A very limited number of lncRNAs have been found to be de-regulated in MM and even less are well characterized. We are using single cell sequencing to study how lncRNAs may promote progression of MM and identify cell subtype expression to determine important roles in this process. Further, we are interested in RNA modifications of lncRNAs in MM, specifically m6A modification and how it affects protein binding.
Regulatory role and therapeutic potential of long non-coding RNAs in metastatic colorectal cancer (mCRC)
Despite advances in our understanding of primary CRC oncogenesis, the mechanisms by which CRC becomes metastatic and leads to patient death is poorly characterized. In addition, the lack of reliable biomarkers to predict development of mCRC is a critical barrier. Dr. Silva-Fisher previously identified RNAs Associated with Metastasis (RAMS11) to be highly important in the regulation of promoting metastasis https://www.nature.com/articles/s41467-020-15547-8. The Silva-Fisher lab continues to evaluate mCRC lncRNAs as prognostic biomarkers and potential novel therapeutics.
TARGETING LONG NON-CODING RNAS AS POTENTIAL THERAPIES
lncRNA as therapeutics
RNA based therapies utilize RNA to treat patients. There is an increasing number of non-coding RNA therapies, including miRNAs and lncRNAs that are being FDA approved for treating multiple diseases. Our lab is currently testing one such therapy called Antisense oligonucleotides (ASOs) that will target lncRNAs to treat colon, breast, and myeloma cancers.
We utilize multiple types of advanced sequencing methods and RNA biology methods to characterize lncRNAs, RNA-protein binding, and RNA modifications.