Abstract of first year rotation work with Dr. Xuedong Liu's Lab at CU Boulder: PRDX6 is a prolific protein in cells that has a multitude of roles in the cell. One of its most prevalent roles is its peroxidase activity. In cancerous cells, activity from PRDX6 can hide them from the body’s immune system. Following a live cell imaging assay involving photochemical activation of lipid peroxidation, this study showed that PRDX6 does have an effect on peroxidase which can be quantified. In most species, the only cysteine residue in the PRDX6 sequence is located at the peroxidase site. However, in human PRDX6, there is a cysteine residue at site 91. This raises the question of whether this extra sulfur atom serves a purpose. To determine if C91 is involved in PRDX6’s peroxidase activity, an intact mass spectroscopy experiment was performed via co-incubation of different purified PRDX6 mutants with PX12. PX12 is a thioredoxin inhibitor that modulates the activity of proteins that protect the cell from reactive oxygen species (ROS). 

Abstract of first year rotation work with Dr. Karolin Luger's Lab at CU Boulder: Exploring specific inhibitors of the protein complex between PARP1 (Poly(ADP-ribose) polymerase 1) and HPF1 (histone PARylation factor 1) is a promising strategy in cancer therapy and other diseases associated with DNA repair dysregulation. This study utilized an automated liquid handling system to efficiently prepare 384-well plates with diverse compound libraries targeting PARP1/HPF1 interactions. The pipetting robot enabled high-throughput compound dispensing, ensuring precision and reproducibility in the preparation of test solutions. These plates were subsequently used to perform a smear gel electrophoresis to assess the inhibition or modulation of PARP1/HPF1 activity in DNA repair processes compared to activity of PARP1 by itself. This method was used to identify potential lead compounds with selective action against PARP1/HPF1, providing valuable insights into their therapeutic potential. The integration of automation in compound preparation and analysis streamlines the process, allowing for the rapid screening of large compound libraries in drug discovery efforts focused on targeted DNA repair pathways.

Abstract of first year rotation work with Dr. Michael Shirts' Lab at CU Boulder: Poly (ADP-ribose) polymerase 1 (PARP1) is a crucial enzyme involved in DNA repair processes and has become an important therapeutic target in cancer treatment. This study investigates the interactions of PARP1 with two different inhibitors (Olaparib and AZD5303) through molecular dynamics (MD) simulations. I prepared the protein-ligand system for the GROMACS molecular dynamics simulation by preparing the protein and inhibitor structures and adding solvent to the model system. After energy minimization and equilibration, I ran a production run to simulate the system’s dynamics and analyze protein-inhibitor interactions. With this model, I explored the structural dynamics, binding affinity, and stability of the inhibitor-protein complexes over time.