Project Title: Transcriptional regulation of the novel Schizophrenia risk gene, PIK3CD
Program: Cell Biology, Stem Cells and Development
Mentor: Amanda Law
My research focuses on alternative splicing and transcriptional regulation of a novel SZ risk gene and a new antipsychotic drug target- PIK3CD. Evidence suggests that regulation of PIK3CD occurs mainly at the transcriptional level and that the gene contains several novel 5’untranslated exons with distinct promoters. A truncated variant, P37, also results from alternative splicing of the PIK3CD gene. In addition, two antisense RNAs, PIK3CD-AS1 and -AS2, have the potential to further regulate PIK3CD gene expression. I am working to uncover the function and mechanistic regulation of PIK3CD transcripts in the brain, as well as in the context of SZ and neurodevelopment.
Project Title: Understanding the structural basis of RNA manipulation of ribosomes by IRES RNAs
Program: Structural Biology and Biochemistry
Mentor: Jeff Kieft
Some viral and cellular RNAs do not use a canonical poly(A) tail. Instead, they use a structured 3’UTR to increase message stability or to enhance the rate of translation. I am investigating these phenomena using the Turnip Yellow Mosaic virus (TYMV) 3’UTR. This 3’UTR has two domains: a tRNA-like structure (TLS) functions as a tRNA mimic driving aminoacylation, and the upstream pseudoknot (UPD) stabilizes the TLS. Using biochemical approaches, I am learning how this RNA manipulates translation, how the UPD functions as a molecular sensor, and how the structure of UPD affects the conformational dynamics of the TLS.
Project Title: The intracellular and extracellular innate immune response to flaviviral infection of the central nervous system
Mentor: Ken Tyler
My work is focused on how host Rig-I-like RNA helicases (RLRs) respond to Flaviviral infection of the central nervous system (CNS). The RLR pathway is essential in the production of type I interferon which propagates an antiviral state within nearby cells and tissues. I utilize West Nile virus, Zika virus, and Japanese encephalitis virus to compare RLR responses in the CNS during viral encephalitis. I am investigating how the CNS responds to very similar pathogens (both in clinical presentation and RNA structure). I see very specific differences between these Flaviviral-induced infections both during early events and downstream cytokine and chemokine production.
Project Title: The role of RNA polymerase II elongation control in transcription dynamics
Program: Molecular Biology
Mentor: David Bentley
The synthesis of RNA by RNA polymerase II is not a smooth and continuous process, but one that is punctuated by frequent pauses and fluctuations in transcription rate. Changes in the elongation phase of transcription not only affect final RNA levels, but also impact RNA processing decisions, and have been linked to a number of human diseases. The goal of my research is to investigate how factors that alter transcription elongation influence the biogenesis of various pol II transcripts including mRNAs, lncRNAs, snRNAs, snoRNAs, and eRNAs.