Current Scholars and Projects

Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by the deterioration and eventual death of central nervous system cells, and it currently lacks a cure. AD directly affects approximately 50 million individuals worldwide and indirectly countless families and caregivers. Amyloid beta plaques are a hallmark of AD, yet therapies targeting these plaques have repeatedly failed over the years, raising doubts about their central role in disease causation. However, growing evidence suggests neuroinflammation as a key factor in understanding neurodegenerative pathology. Therefore, our research aims to develop tools for modeling and investigating neuroinflammation.
Microglia, astrocytes, and neurons are key to understanding neurodegeneration and neuroinflammation. Microglia serve as the brain's immune responders. Astrocytes regulate the chemical environment. Neurons, responsible for transmitting electrical signals, become vulnerable to damage during neuroinflammatory events.
Traditional monoculture models inadequately represent neuroinflammation due to their inability to capture essential cell-to-cell communication. Existing polyculture models better reflect biological complexity but often rely on expensive materials and specialized techniques that limit accessibility to researchers. To overcome these limitations, we are developing a novel, entirely human-derived triculture system incorporating microglia, astrocytes, and neurons designed to be cost-effective and broadly accessible to researchers while maintaining biological complexity.
We will utilize multiple analytical techniques to investigate cellular interactions within our triculture system under pro- and anti-inflammatory stimuli: RNA sequencing, western blotting, high-performance liquid chromatography (HPLC), and microchip electrophoresis with laser-induced fluorescence detection (ME-LIF). My research will focus on RNA sequencing and ME-LIF analyses. These techniques will collectively yield transcriptomic, proteomic, and metabolomic data about cellular function and communication. Ultimately, our goal is to provide researchers with an effective and practical tool capable of accurately modeling the complex biology of the brain, thus accelerating meaningful progress in neurodegenerative disease research.

The project I intend to pursue is the investigation of sulfation patterns in a rodent model. The sulfation pattern will be seen in a specific constituent of the extracellular matrix (ECM) called chondroitin sulfate proteoglycans (CSPGs). When demyelination occurs, a glial scar is formed, the glial scars have a higher concentration of CSPGs. CSPGs are a protein core with chondroitin sulfate (CS) glycosaminoglycan (GAG) disaccharide chains. The different sulfation patterns are CS-A, CS-C, CS-D, and CS-E. Dr. Linda C. Hsieh-Wilson’s lab has demonstrated that distinct sulfation motifs serve as molecular recognition elements for various neuronal activities, including growth and repair.
In this project, we are interested in whether sulfation patterns can affect remyelination. The specific sulfation pattern being monitored is CS-E. This work is based on Jenna William’s thesis on CS-GAG’s inhibition of neuronal growth in the CNS. In Jenna’s project, the strain utilized was a conditional gene knockout of carbohydrate sulfotransferase 11 (Chst 11). Through this experiment, it was shown that CSPGs have inhibitory effects on cell growth and remyelination.
This project will utilize the cuprizone model of demyelination for the mice. The mice utilized in this experiment are the Chst15 KO mice. Chst 15 is the gene responsible for creating CS-E. These will be 6-week studies. The mice will be bred to create the colony and genotyped. The mice will be weighed each week, and their disease progression will be scored. At the end of each 6-week study, the mouse will be perfused and the brain and spinal cords removed. Once all mice have been collected, the brains will be stained and imaged using a combination of histology, immunofluorescence, and electron microscopy.
If CS-E is responsible for blocking remyelination, the effect will be with a lack of CS-E there will be an increase of myelination.

The Beck Lab is interested in using threespine stickleback fish as a model to study mitochondrial (mito)-nuclear genomic interactions. We use stickleback because of the co-existence of two extremely divergent mitochondrial haplotypes (mitotypes) in Alaska. These mitotypes have extremely high sequence-level divergence allowing us to ask questions about how the nuclear genome evolves to compensate for mitochondrial variation. Understanding mito-nuclear interactions is important because incompatibilities between these genomes can lead to mitochondrial dysfunction which underlies common diseases like Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and more. Stickleback do not obviously present mitochondrial dysfunction phenotypes despite their high levels of mitogenomic variation. This suggests that the nuclear genome is compensating to support significantly different mitotypes. We want to understand these compensatory mechanisms.

In Aim 1, the ratio of mitotypes in arctic-adjacent stickleback populations will be assessed. This will be done by first isolating the DNA from 24 Alaskan stickleback from two separate populations (n = 48), amplifying the ctyb region of the mitogenome by PCR, and performing a restriction digest which cuts DNA differently based on the organism’s mitotype. The restriction digest will allow us to determine the mitotype of each fish. If the two mitotypes prove to have approximately equal presence, we will have the option to conduct a Genome Wide Association Study (GWAS) of this population to identify correlated changes in the nuclear genome.

In Aim 2, I will investigate the role that temperature has played in mitochondrial adaptation in stickleback. To accomplish this, I will learn how to perform high molecular weight DNA extraction for long-read sequencing, learn about Nanopore sequencing technology, and learn basics of genome assembly and annotation to compare arctic-adjacent mitogenomes to those of stickleback in more temperate climates.