Merci N. Best, PhD, MS

As an undergraduate student, I minored in Community Studies because of my participation in the Sharpe Community Engagement Scholars Program. I volunteered in a second-grade math classroom as a tutor. In parallel, I researched the ways teachers contributed to the "leaky science, technology, engineering, mathematics (STEM) pipeline" for girls.

I later researched the "leaky STEM pipeline" for Black children. To combat against summer learning loss and lack of role models as contributions to "leaky STEM pipeline" for both girls and Black children I developed STEAMTRIX, a summer intervention program designed to introduce students to STEM by incorporating the visual and performing arts.

To increase the scalability of my efforts, I recently founded STEAMKITX, an education company that sells STEM and art activities that empower students to explore science and related careers.

usingy third and final rotation through the Biomedical Sciences Graduate PhD Program was in Dr. George Bloom’s laboratory. As a rotation student, I re-established the use of a former graduate student’s protocol to study the effect of secreted tau on neurons. In doing so, I learned how to maintain primary mouse neurons in culture and optimized protocols for tau protein purification, oligomerization, and cell-culture-based immunocytochemistry, and western blot. My work resulted in authorship on a peer-reviewed publication and presentations.

My published dissertation, "Breaking Barriers: A Quantitative Analysis of Axon Initial Segment Disruption in Neurodegenerative Disease", overviews the first evidence suggesting a functional connection among neurofibrillary tangles, tau oligomers, and axon initial segment disruption. To do so I led a diverse team of biologists, neuroscientists, pathologists, and undergraduate trainees at the University of Virginia. Specifically, we quantified AIS disruption in human postmortem brain tissue and mouse cell culture. These findings resulted in first authorship on a peer-reviewed publication, conference presentations, and a defended dissertation.

I worked as an intern at Denali Therapeutics for three months. During my time there I collaborated with scientists across multiple departments and independently led a novel project from piloting through analyzing.

The project was very ambitious and it was noted in a letter of recommendation that my collegial spirit and can-do attitude among my intellectual curiosity, outstanding organizational skills, and tenacious work ethic enabled me to complete this project in a short amount of time. I gained a number of new technical skills for the project. At the end of my internship, I presented my work to over two dozen biologists, chemists, protein scientists, pharmacologists, and non-scientists. I was able to communicate both the broader importance as well as the experimental findings of the study in a way that was accessible to everyone in the room. I had to thoroughly understand the background and rationale for the project, interpret all the data, and distill the conclusions into logical next steps for future scientists to pursue.

I developed organizational skills and generated a lot of data which I kept detailed in electronic notebook protocols that I wrote for the 25+ experiments I conducted while at Denali. The results have generated a large impact on Denali’s future directions.

I came to Denali driven by my passion to understand the molecular mechanisms of neurodegeneration, and the desire to learn how basic biology questions are then translated into therapeutic discoveries and ultimately medicines. I learned that I am committed to a future in research. At Denali, I benefited by being able to realize my desire to understand the larger implications of my work on Alzheimer’s disease at UVA. I was also surrounded by a community of like-minded individuals who reaffirmed my intellectual drive, technical acumen, and grit.

As an undergraduate, my first project was assisting a junior lab member in characterizing a somatic cell driver transgene during Drosophila testis development. We worked as a team to develop testable hypotheses, perform sonication-facilitated immunofluorescence staining of tissues in situ, and characterize the expression of transgenes. Our work created a chart of gene expression patterns during development that I used in my undergraduate Honors Thesis research project.

To elucidate the role of an evolutionarily conserved cell signaling pathway in the early stages of Drosophila testis development, I drove tissue-specific expression knockdown of the Bone Morphogenic Protein (BMP) signaling pathway. My thesis resulted in three major accomplishments.

First, in collaboration with a former lab member, I successfully characterized the loss of BMP signaling during embryonic and early first instar larval (L1) stages of Drosophila testis development. Secondly, I independently discovered a role for BMP signaling in preventing premature germ cell differentiation during late embryonic and early L1 stages. Finally, I wrote and defended an Honors Thesis publication, which is published as a preprint, and submitted to PLoS One.