Dr. Katie Mouzakis earned her B.S. in Chemistry-Biology (joint major) from Harvey Mudd College; not far from her hometown of Rancho Cucamonga, CA. She received her Ph.D. in Biochemistry from the University of Wisconsin – Madison (UW Madison). During her graduate and postdoctoral work (also at UW Madison), she used biochemical, biophysical, and computational methods to study viral RNA structures and their functions. Concurrently, she gained invaluable teaching experience through the HHMI Teaching Fellows Program. Dr. Mouzakis comes to LMU from Durango, CO, where she was an Assistant Professor of Biochemistry at Fort Lewis College (FLC). At FLC she established an undergraduate-driven, externally-funded research program, was awarded the FLC New Faculty Teaching Award, and was named a 2017 Cottrell Scholar by the Research Corporation for Science Advancement for her innovative research and educational programs. Her work is published in numerous journals, including Nucleic Acids Research, PNAS, and RNA. Dr. Mouzakis joined LMU’s Department of Chemistry and Biochemistry in 2018. She is thrilled to continue work she loves, teaching and doing research with undergraduates, as a faculty member at LMU.
Univeristy of Wisconsin-Madison: Ph.D., Biochemistry 2013
Harvey Mudd College: B.S., Joint Major in Chemistry-Biology 2007
Areas of Expertise (5)
Course-based Undergraduate Research Experiences
Programmed Ribosomal Frameshifting
Nucleic Acids Biochemistry
Research Grants (3)
COVID Initiative Award
Research Corporation for Science Advancement $55,000
Viral RNA structures are known to regulate replication but are underexplored as drug targets. In this work, we propose to identify the first antivirals that target a SARS-CoV-2 RNA structure critical to translational reprogramming. By leveraging the complementary expertise of Dr. Mouzakis (LMU), Dr. Hargrove (Duke), and collaborators (Dr. D’Souza [Harvard], Dr. Brewer and Dr. Li [Rutgers]) we will identify the first SARS-CoV-2 antivirals that modulate its frameshift site (FSS) RNA structure, ultimately inhibiting viral replication. Advances made are likely to be transferable, at least in part, in the targeting of other viral RNA structures and will expand antiviral drug development opportunities to address the current and future viral pandemics.
Cottrell Scholar Award
Research Corporation for Science Advancement $100,000
Programmed ribosomal frameshifting (PRF) is a common viral mechanism used to regulate the levels of viral enzymatic and structural proteins. How RNA structures induce a one nucleotide (-1) PRF is a fundamental question of relevance to human health, due to its prevalence in retroviruses that infect and cause human diseases. Here, we propose to determine the basis of structure-stimulated -1 PRF in the human T-cell lymphotropic virus type I (HTLV-I) retrovirus. HTLV-I’s two frameshift sites are located at the gag-pro and pro-pol open reading frame junctions. We aim to determine the length and structure of the HTLV-I pro-pol frameshift site, and to investigate the relationship between the gag-pro structure’s thermodynamic stability and -1 PRF efficiency. These studies will provide fundamental insight into role of the HTLV-I frameshift site structures in -1 PRF.
SCORE SC2 Award
National Institutes of Health (NIGMS) $300,000
Programmed ribosomal frameshifting (PRF) is a common viral mechanism used to regulate the relative levels of various gene products. How RNA structures induce PRF is a fundamental question of relevance to human health, due to its prevalence in retroviruses that infect and cause human diseases. Human T-cell lymphotropic virus type I (HTLV-I) replication depends on two -1 PRF events, which occur at the gag-pro and pro-pol open reading frame junctions. How the cis-acting RNA elements at these genomic locations function to induce frameshifting is unknown. The long-term goal of this research is to improve understanding of how viral RNA structures manipulate host-translational machinery to ensure successful viral replication. The overall objective of this application is to determine the structural basis of -1 PRF in the HTLV-I retrovirus. Our central hypothesis is that specific regions of thermodynamic stability within each frameshift site structure are fundamental to frameshift stimulation. The rationale that underlies the proposed research is that once the structural basis of -1 PRF is understood, a significant gap in the knowledge base about the HTLV-I frameshift mechanisms would be filled. We propose two specific aims: 1) Define the HTLV-I frameshift site RNA structures, and 2) Investigate the relationship between each structure’s local thermodynamic stability and -1 PRF efficiency. In this proposal, local thermodynamic stability is defined by the stability of base-pairs positioned directly outside of the mRNA entry channel at the time of frameshifting. To accomplish these aims, RNA chemical probing experiments will be combined with computational methods to define the RNA secondary structures at each frameshift site. Mutagenesis and in vitro frameshift assays will be used to evaluate the importance of each structure to -1 PRF and to investigate the relationship between local thermodynamic stability and frameshift efficiency. The results of the proposed research are significant because they will substantially increase what is known about HTLV-I structure-stimulated programmed ribosomal frameshifting. These studies promise to open new research horizons, particularly in targeting HTLV-I frameshift sites as a means of disrupting HTLV-I replication.