As a graduate student, I solidified my love for lipid biology. As a postdoc, I sought to expand my toolkit beyond cell culture, and dive more deeply into the cellular pathways that govern lipid metabolism, specifically, the mechanics of lipoprotein biosynthesis. The basic cellular biology of lipoprotein biosynthesis plays a role in the levels of circulating lipids, which are a key factor in metabolic diseases which impact 1.2 billion people worldwide. The zebrafish model is an excellent system to study the cellular biology of lipoprotein biosynthesis: 1) cellular machinery required for lipoprotein construction is conserved between zebrafish and humans, 2) many important reporters have been developed and allow us to observe cellular processes in the context of intact organ systems. I chose to work with Dr. Steven Farber for my postdoctoral work because of the key role he and his lab have played in establishing the zebrafish as a model for the study of lipid metabolism. In his lab, I leveraged a phenotype, unique to the zebrafish, that is associated with abnormal lipoprotein metabolism to conduct a forward genetic mutagenesis screen in order to identify genes involved in this important biology. Over two years, my team of a dozen undergraduates and Farber lab staff screened ~500,000 zebrafish embryos representing ~1,000 mutant families in order to identify 28 dark yolk mutants. In order to identify the causative mutation for each of these mutants, I collaborated with Aleksey Zimin and Steven Salzberg to develop a hybrid mapping-by-sequencing:positional-cloning pipeline, called WheresWalker, which we have used to map several of the mutants in the collection. Mapping is ongoing, but with each new mutant mapped, we are discovering interesting genes, many of which have not yet been linked to lipoprotein biology. I have become particularly interested in the zion mutant, which maps to the amino acid transporter slc3a2a. SLC3A2 interacts with SLC7 family members to transport different substrates. These SLC3A2/SLC7 dimers are particularly exciting and important, because many SLC7 family members contain human variants associated with dyslipidemia phenotypes.
Teaching and mentoring: Undergraduate involvement in zebrafish husbandry and mutant characterization has been key to the success of the screen. In total, I have mentored 5 undergraduate students in their screen-based research projects, and 3 undergraduate student employees. In addition, I have mentored 3 graduate students through rotation projects and 1 masters student through thesis.
Research Support and Recognition:
Conference Participation: Presentations (⧈) and Posters (▢)
Under the supervision of Drs. Dan Ory, Jean Shaffer, and Doug Covey, I investigated the itinerary of intracellular cholesterol trafficking after uptake to the lysosome in LDL particles. Through this work, I characterized novel diazirine alkyne cholesterol probes for use in cholesterol interactome and subcellular localization studies, and investigated the mechanisms by which cyclodextrin, and other small molecules, remodel cholesterol trafficking to ameliorate abnormal lysosomal cholesterol storage caused by NPC1 deficiency.
Teaching and mentoring: Over the course of my graduate career, I served as teaching assistant for Chemistry and Physics of Biomolecules (BIOL5357) and guest lectured for Molecular Biology at the Cutting Edge (BIOL 4933). I took numerous courses on best practices in mentoring and teaching. During my tenure, I was able to mentor 3 young scientists, and serve as mentor for the NIH Fellowship Writing Workshop. In addition, I served as both a director and mentor for the Young Scientist Continuing Mentoring Program - a 4 year mentoring program that pairs graduate students with local high school students and includes exciting scientific teaching activities - where I played a key role in redesigning the curriculum.
Research Support and Recognition
Conference Participation: Presentations (⧈) and Posters (▢)
As an undergraduate at Drury University, I worked in the lab of Dr. Albert Korir where I began developing a skill set in analytical chemistry. Heparin and other glycosaminoglycans (GAGs) are long unbranched polysaccharides that mediate a variety of cellular processes including cell differentiation, proliferation, metastasis, and inflammation but do so by incompletely understood mechanisms. To gain insight into GAG biology, I developed an affinity capillary electrophoresis (ACE) method to quantitatively measure GAG binding interactions. I gained further research experience in analytical chemistry through an internship at DuPont Industrial Biosciences under the mentorship of Dr. Donald Cannon. As an Intern, I studied metabolites involved in yeast stress response. Fuel ethanol is produced by the fermentation of corn products by yeast. While ethanol is the desired product, yeast produce many other metabolites during fermentation and become less efficient at producing ethanol when subjected to stresses such as heat and osmotic imbalance. I used liquid chromatography to monitor the levels of several metabolic intermediates under different fermentation conditions to identify new biomarkers of yeast stress.
Teaching and mentoring: I served as teaching assistant for Analytical Chemistry Lab (CHEM 208L) for two semesters. As the senior member of Dr. Korir’s research group, I also served as a mentor to other undergraduate researchers.
Support and recognition:
Conference Participation: Presentations (⧈) and Posters (▢)