Current Scholars and Projects


Project Spotlights

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Maggie Ridgway

Project Title: Gene-Metal-Microbe Interactions: Investigating Heavy Metal Response and Microbiome Dynamics in Drosophila

Heavy metals like manganese, cadmium, and lead are widespread environmental contaminants that pose serious health risks to humans and animals. While some metals are essential in trace amounts, excessive exposure can disrupt biological systems and contribute to diseases. My research focuses on understanding how genetic factors and gut microbiota influence resistance to heavy metal toxicity using Drosophila melanogaster as a model organism.
In previous work, I studied a gene called pHCl-2, which encodes a chloride channel, and found that loss-of-function mutations in this gene reduce fly survival after manganese exposure, suggesting a role in metal detoxification. However, this effect did not extend to cadmium or lead, pointing to metal-specific genetic responses.
Building on this, my current project investigates how heavy metal exposure affects the composition of the gut microbiome, and whether the microbiome in turn influences host resistance to metals. I rear flies from multiple genetic backgrounds on diets supplemented with different heavy metals, then extract and sequence bacterial DNA from their guts to assess microbiome changes using 16S rRNA metagenomic techniques. I also plan to generate axenic (microbiome-free) flies from inbred strains with known resistance levels to test how the absence of microbiota alters their metal tolerance.
This project aims to reveal new insights into the complex interactions between host genetics, environmental stressors, and microbial communities. Understanding how microbiomes contribute to metal resistance may help us better grasp the biological mechanisms that maintain metal homeostasis—knowledge that could ultimately inform therapeutic strategies for managing metal toxicity in humans.
Project Mentor: Stuart Macdonald

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Parnian Arafi

Project Title: PSEN-1 and APP-Mutant γ-secretase complexes stall amyloid beta peptide production

My research focuses on understanding the molecular mechanisms underlying familial Alzheimer’s disease (FAD), with an emphasis on the role of Presenilin-1 (PSEN-1) mutations and their impact on γ-secretase activity. Specifically, I study how these mutations influence the production and processing of amyloid-β (Aβ) peptides, including Aβ42 and Aβ40, which are central to plaque formation in Alzheimer’s disease (AD). Although the Aβ42/Aβ40 ratio has long been considered a critical marker of disease progression, our findings reveal a more complex picture.
We have shown that AD-related PSEN-1 mutations disrupt specific proteolytic steps in γ-secretase processing, leading to the accumulation of stalled enzyme-substrate complexes. These complexes, rather than the final Aβ products themselves, appear to drive synaptotoxicity and neurodegeneration. Using in vitro assays and in vivo C. elegans models, we analyzed six common PSEN-1 mutations and found no consistent elevation in the Aβ42/Aβ40 ratio. Instead, each mutation impaired a distinct cleavage step in the γ-secretase pathway.
To expand on these findings, I am currently preparing DNA constructs and proteins for 21 additional PSEN-1 mutations. My goal is to determine whether a common mechanism of stalled complex formation underlies a broader range of mutations.
Additionally, my work includes the biochemical and histological characterization of mouse models harboring knock-in mutations in the amyloid precursor protein (APP). Additionally, I investigated the effects of these mutations on Aβ production, plaque deposition, and regional gene/protein expression. This involved spatial transcriptomics, proteomics, immunohistochemistry, and ELISA to quantify various Aβ fragments.
Altogether, my research aims to redefine our understanding of how pathogenic mutations contribute to AD and to identify novel mechanistic targets for therapeutic intervention.
Project Mentor: Michael S. Wolfe

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Meghan Arias

Project Title: Determining if PARP14 Restricts HSV-1 Replication in a Strain-Dependent Manner

      Herpes simplex virus 1 (HSV-1) is a common human pathogen that primarily causes oral sores during the lytic stage of its replication cycle. HSV-1 can significantly threaten human health, especially in immunocompromised individuals. Eye infections can lead to corneal scarring, which may cause blindness, and infections of the spinal cord or brain can lead to life-threatening conditions like herpes meningitis or encephalitis. The World Health Organization estimates that over 67% of people globally are infected with HSV-1. Current treatments reduce visible symptoms but do not eradicate the virus which lies dormant in sensory neurons. Reactivation of the virus from latency can be stimulated by stress, hormonal changes, and DNA damage, leading to further lytic replication.
      PARP14 is a host protein that has been found to have an antiviral effect against wild-type HSV-1. My project aims to determine whether PARP14 functions in a strain-specific manner by testing its impact on a more pathogenic strain of HSV-1 known as strain 17. This process involves performing plaque efficiency assays with strain 17 and five different A549 human lung carcinoma cell types (two controls and three PARP14 knockout variants). In addition, I will explore where in the viral replication cycle PARP14 exerts its inhibitory effects by using quantitative Polymerase Chain Reaction (qPCR) to measure viral mRNA transcripts and western blots to measure viral protein expression at various timepoints.
      It is expected that the results of this study will provide researchers with a better understanding of PARP14's antiviral mechanisms against HSV-1 and thus contribute to the development of potential treatments for HSV-1 infection, ultimately improving patient outcomes.
Project Mentor: David Davido

All Current Scholars and Projects

List of Current Scholars and Projects

StudentProject TitleMentor
Parnian Arafi PSEN-1 and APP-Mutant γ-secretase complexes stall amyloid beta peptide production Michael S. Wolfe
Meghan Arias Determining if PARP14 Restricts HSV-1 Replication in a Strain-Dependent Manner David Davido
Vincent Chan Resistance to X chromosome meiotic drive in Drosophila affinis Rob Unckless
Kendall Cranor  Incorporation of Chimeric Macrodomains into Murine Hepatitis Virus (MHV) to Test Antivirals Against Multiple Coronaviruses Using a Single Viral System Tony Fehr
Jim Krentzel Studying the genetics of flower symmetry using CRISPR/Cas9 gene editing Lena Hileman
Leah Legleiter Regulation of cdeAB-oprM efflux pump in Chromobacterium subtsugae in response to antibiotics and quorum sensing Josie Chandler
Diego Prieto Determining the Impact of RsbV1's Phosphorylation State for Chlamydia trachomatis’ Growth and Progeny Production Scott Hefty
Maggie Ridgway Gene-Metal-Microbe Interactions: Investigating Heavy Metal Response and Microbiome Dynamics in Drosophila Stuart Macdonald
Ariana Siddique Permeabilization of C. elegans cuticle using gene silencing for the needle-free delivery of chemicals Lisa Timmons