Projects and Publications

Below you will find my BioSketch, as well as descriptions of scientific projects and contributions I have made throughout my scientific career.

Biosketch

Undergraduate Research

Project #1:

As an undergraduate, I was fortunate to meet and be accepted into the lab of Dr. Frederick Domann, a Professor in the Free Radical and Radiation Biology Program (FRRBP) at the University of Iowa (UIowa). I was entrusted with a research project focused on understanding the effects of manganese superoxide dismutase (MnSOD) knockout in human cells by utilizing the CRISPR/Cas9 gene editing system to disrupt the SOD2 gene. This project successfully established the first MnSOD knockout human cell line and stimulated my desire to pursue my doctoral degree in FRRB. The results were published in Free Radical Biology and Medicine in the Fall of 2015.

SOD2 targeted gene editing by CRISPR/Cas9 yields Human cells devoid of MnSOD

Graduate Research

Project #2:

In my first few months in Dr. Spitz’s lab, I hypothesized and confirmed that the clinically-available superoxide dismutase (SOD) mimetic GC4419 enhances the oxidation and anti-cancer effects of pharmacological ascorbate (AscH). I demonstrated that the Mn(II)-containing SOD mimetic GC4419 significantly enhanced the toxicity of AscH in lung and head and neck cancer lines most likely by serving as an AscH/O2•- oxidoreductase. I gained experience in redox chemistry while showing that the enhanced cancer cell killing capacity of GC4419 and AscH was dependent upon the catalytic activity of the SOD mimetic and the generation of H2O2. These results were presented at the SFRBM National Meeting in 2017, where I received a Young Investigator Award. The results were then published in the peer-reviewed journal Antioxidants in January 2018. This project is particularly exciting because it suggests that combination of these two agents may lead to enhanced anti-cancer effects. During this project, I gained significant experience in cell culture, molecular techniques, EPR spectroscopy and understanding of redox physical chemistry regarding some of the most exciting redox-active anti-cancer and normal tissue protective agents currently in clinical trials.

Superoxide dismutase mimetic GC4419 enhances the oxidation of pharmacological ascorbate and its anticancer effects in an H2O2-dependent manner

Project #3:

In the Fall of 2017, began to develop a my dissertation project related to understanding and exploiting inherent differences in cancer cell metabolism. After a significant amount of literature research, I became intrigued by understanding and exploiting NAD+ metabolism in tumor cells, specifically through targeting of the enzyme nicotinamide phosophoribosyltransferase (NAMPT). We have shown that NAMPT inhibitors are selectively toxic to cancer cells, induce metabolic oxidative stress, and confer potent sensitization to radio-chemo-therapies that induce PARP-DNA complex formation. In addition, I have co-authored a review article regarding mitochondrial metabolism in cancer therapy in which I provided figures and insights regarding the interface between salvage-pathway NAD+ synthesis and hydroperoxide metabolism (see below).

Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy