Who Is Merci Best?
A daughter, sister, niece, cousin, friend, mentor, scientist & entrepreneur.
Postdoctoral Fellow, The University of Michigan
After earning my Bachelor of Science in Neuroscience from the College of William & Mary and my Doctorate of Philosophy in Pharmacology from the University of Michigan, I started my postdoctoral fellowship at the University of Michigan on June 1, 2023.
Founder of STEAMKITX, STEM & Arts Kits
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.
I studied the cell biology of an early event in Alzheimer's disease.
Aim 1- Is there evidence of axon initial segment disruption in humans with Alzheimer's disease?
I performed immunohistochemistry and western blot analyses of "normal" and "Alzheimer's disease" donor brain tissue to measure axon initial segment structure and protein levels.
Aim 2- Do human recombinant tau oligomers cause axon initial segment disruption?
I performed protein purification, protein oligomerization to create tau oligomers. I performed immunocytochemistry and western blot analyses of tau oligomer- and no tau containing vehicle control- treated mouse cell culture to measure axon initial segment structure and protein levels.
Aim 3- What is the mechanism of axon initial segment disruption?
I performed genetic and pharmacological inhibition to modulate a cell signaling pathway. I performed immunocytochemistry and western blot analyses of lentivirus- and pharmacological inhibitor- treated mouse cell culture to measure axon initial segment structure and protein levels.
Breaking Barriers: A Quantitative Analysis of Axon Initial Segment Damage in Neurodegenerative Diseases
Axon initial segment (AIS) damage has been implicated in several neurodegenerative diseases (NDs). Nevertheless, it is unknown whether systematic damage to the AIS is a unifying feature among Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, multiple sclerosis, and Parkinson’s disease. In this dissertation, it was hypothesized that 1) AIS structural and functional damage occurs in NDs, 2) extracellular tau oligomers (xcTauO) cause damage to the AIS, and 3) xcTauOs cause AIS protein, tripartite motif-containing protein 46 (TRIM46) and lysosomal-associated membrane protein 1 (LAMP1)+ organelles to co-localize. A systematic literature review, quantitive western blots, and quantitative immunofluorescence were performed. The literature review identified 42 studies that quantified 14 AIS structural and two AIS functional parameters in five NDs. The data chapters found that xcTauOs work through intracellular tau to cause a reduction in AIS immunofluorescent intensity as a semi-quantitative measurement of localized protein abundance and AIS shortening. These same xcTauOs also increase AIS protein, TRIM46, and LAMP1 co-localization. Overall the work presented in this dissertation demonstrates that the AIS can be damaged by xcTauOs in NDs.
Click here to access my dissertation.
Where My Research Experiences Have Taken Me
I have been conducting scientific research since middle school.
The University of Michigan - Ann Arbor, MI
At the University of Michigan, in Dr. Henry L. Paulson's laboratory, I am exploring the mechanism(s) of tau-mediated neurodegeneration in tauopathy with a specific interest in Frontotemporal dementia (FTD), Alzheimer's disease (AD), Progressive supranuclear palsy (PSP), and Chronic Traumatic Encelphathopy (CTE). I am mentored by Dr. Paulson alongside Drs. Sami Barmada, Paul Jenkins, Kevin Jones, and Catherine Kaczorowski.
The University of Virginia - Charlottesville, VA
2018 - 2023
My 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.
Virginia Discovery Museum - Charlottesville, VA
I spent the Spring 2022 semester interning as a Virginia Discovery Museum Fellow. The museum fosters intellectual curiosity and development for all children of our community. I collaborated with the VADM education manager to conceptualize an offering for older children. I created publicly accessible science content in the form of an interactive pop-up exhibit. I planned and executed a hands-on workshop to engage students with my dissertation research.
Denali Therapeutics - San Francisco, CA
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.
Marine Biological Laboratory
As an extension to my interdisciplinary graduate training at UVA, during the summer of 2019, I was accepted to the NINDS sponsored Summer Program in Neuroscience Excellence and Success (SPINES) at the Marine Biological Laboratory in Woods Hole, MA. SPINES is a national program with an over 20-year track record of training successful neuroscientists from underrepresented backgrounds to be leaders in neuroscience.
As a SPINES fellow, I was trained in professional development and neuroscience approaches. I actively participated in workshops that honed important professional skills like networking, scientific communication, mentoring, ethics, honors, and service in preparation to be a principal investigator in academia. I was instructed by 20 faculty from across the country over a three-week intensive immersion experience.
In parallel, I participated in a zebrafish behavioral neuropharmacology lab, which provided me with training in computational MATLAB programming, animal model selection, and high-resolution imaging. I worked in a team to design, perform, and analyze primary data from psychopharmacological experiments utilizing larval and adult zebrafish as a model system. In addition to the class-facilitated experiments, I designed two additional experiments using memantine, an FDA-approved drug for treating moderate to severe Alzheimer's disease. In larval zebrafish, we used single-cell light-sheet microscopy to test the hypothesis that memantine could alter the effects of alcohol on neuronal activity. Using a transgenic zebrafish line with a calcium indicator as a measure of neuronal activity, we found that memantine could rescue alcohol-induced increases in calcium back down to basal levels. In adult zebrafish, we used video tracking software and an original MATLAB code to test the hypothesis that memantine could rescue the effects of stress on adult zebrafish's anxiety-like locomotion behaviors. We found that memantine reversed anxiogenic behavior to what seemed to be anxiolytic behaviors following a stress insult.
The College of William & Mary - Williamsburg, VA
2014 - 2017
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.
The University of Richmond - Richmond, VA
As a high school senior, I spent two half-days each week at the University of Richmond in a voluntary senior mentorship program that allowed me to graduate with an advanced diploma. I examined a role for the gene basket in Machado Joseph Disease (MJD). Motivated by scientific inquiry, I independently used cryogenic and confocal microscopy to examine protein aggregate formation in the Drosophila eye.
My results supported a novel role for basket in autophagy, aggregate formation, and MJD. This research has the potential to help shape the knowledge of humans with MJD and possibly other neurodegenerative diseases. To share these findings, I wrote a 30-page senior thesis and presented it to a diverse audience of teachers, peers, and family.
The University of Richmond - Richmond, VA
To diversify my research experiences at the University of Richmond, in Dr. Malcolm Hill’s lab I worked with Sarah to investigate the evolutionary ecology of species interactions in tropical and temperate marine environments.
The University of Richmond - Richmond, VA
I spent the summer after eighth grade at the University of Richmond (U of R) in a full-time collaborative research experience called Math and Science Investigators (MSI): Richmond. I worked with an undergraduate student Hersh Gupta and his mentor, Professor John Warrick. We investigated the effects of human polyglutamine disease on neurogenetic behavior in the common fruit fly, Drosophila melanogaster. We compared the most common dominantly inherited ataxia, Spinocerebellar Ataxia Type 3, also known as Machado Joseph Disease to wild type.
To study this phenomenon, we maintained stocks, created genetic crosses, performed immunohistochemistry, and western blotting in concert with proteomics studies. This research experience strengthened my scientific proficiency by providing me with a broad set of knowledge in the areas of biology, neuroscience, and genetics. Additionally, I presented our research findings in a formal presentation for professors at the U of R and the director of the MSI program.
See A Need, Meet A Need
I have over eight years of experience in the community engagement and entrepreneurial space working. In. doing so I have worked with numerous community partners, press, and organizations including the following:
Greenstone on 5th
UVA Idea Fund
"STEAMTRIX - Make Your Summer Sweet Program"
"When Fear Meets a Community"
Boys & Girls Club
"STEAMTRIX - Make Your Summer Sweet Program"