I am currently working on genetic mapping of phenotypic and gene expression variations among various Saccharomyces species that are genetically as distant as birds and humans. Using CRISPR/Cas9 gene editing, large scale interspecific hybrid progenies are generated to study genetic architecture contributing to trait variations over long evolutionary distances. These maps enable future functional genomic studies to understand functional divergence and evolution of new molecular functions.

Meta-analysis of Gene Expression Across Species:

I analyze published allele-specific expression (ASE) datasets from plants, yeasts, insects, and animals to understand how gene expression is regulated. Specifically, I focus on the roles of cis- and trans-regulatory mechanisms in driving gene expression variation, and I explore how both biological factors and technical aspects of experiments influence these patterns.

Evolutionary Dynamics of Gene Regulation using Phylogenetics:

Using ASE data from interspecies hybrids within the genus Saccharomyces, I investigate how gene regulation evolves over time. By applying phylogenetic approaches, I study the rate, direction, and underlying mechanisms of changes in gene expression, aiming to uncover the evolutionary forces shaping regulatory variation.

My work focuses on the evolution of gene regulatory mechanisms between species. While we can readily detect expression differences between species, classic approaches can’t distinguish the lineage on which changes in expression occurred. To address this question, I use comparisons among multiple hybrids of Saccharomyces yeast species to polarize cis- and trans-regulatory differences along a phylogeny. In addition, I am extending this approach to inter-genera comparisons between Saccharomyces and Naumovozyma castellii to explore longer term evolutionary patterns. Finally, I am exploring the effects of regulatory backgrounds on estimates of regulatory divergence by manipulating and controlling the inheritance of mitochondria among these hybrids.

I am currently working with Aparna on creating interspecies hybrids that are used for genetic mapping and other purposes. I am currently the main user of our dissection microscope in our lab, which is used to dissect spores from our yeast tetrads, to obtain viable meiotic progeny. These progeny can be screened for crossover events, which are needed for genetic mapping. This method is also used to obtain haploid versions of the yeast that are dissected. 

Aside from interspecies hybrids, I am working on a novel technique for studying genetic mapping among Saccharomyces yeast that involves crossing a sporulated hybrid yeast with a third strain to rapidly identify hybrid progeny that successfully went through meiosis.

My research asks how homologous transcription factors evolve different regulatory programs despite pleiotropic constraint. Using Saccharomyces cerevisiae and Saccharomyces eubayanus in a hybrid yeast system, I combine reciprocal hemizygosity, promoter swapping, and RNA-seq to quantify how often transcription factors diverge and whether divergence is driven mainly by changes within promoters or coding regions. I also test the extent to which differences in regulation change across environments and use ancestral reconstruction to determine how regulatory divergence accumulates across lineages.

One of the major barriers to genetic mapping between distant species is that the two species' sequences may be too divergent to recombine efficiently during hybrid meiosis, resulting in chromosome missegregation and aneuploidy. Currently, I’m trying to improve the individual hybrid fertility of two yeast species, Saccharomyces kudriavzevii & Saccharomyces arboricola. Using CRISPR, I am replacing the promoters of genes involved in mismatch repair to alter expression during meiosis.

My work in the Metzger Lab focuses on building computational tools to better understand how proteins evolve. I help develop and run an automated sequence-analysis pipeline that compares genes across many species to produce reliable evolutionary alignments, a key step for reconstructing ancestral proteins and studying how new molecular functions emerge. Using ensemble alignments from MUSCLE5 together with an optimized, more memory-efficient implementation of CLOAK and a custom condensation workflow, this approach reduces alignment bias, handles large datasets, and preserves important evolutionary information. By making these analyses more scalable and reproducible, this work supports broader efforts in the lab to investigate how chance, history, and biochemical constraints shape protein evolution.

I currently work on the specific contributions of genetic distances and chromosomal rearrangements to reproductive isolation. I’m doing this by reverting a chromosomal translocation between Saccharomyces eubayanus and Saccharomyces uvarum using CRISPR. I am then comparing how this change affects hybrid spore viability compared to increases in recombination to determine the relative effects of genetic distances and chromosomal rearrangements. Prior to this project, I’ve worked on evaluating the roles of chance, contingency, and necessity in the evolution of tyrosine kinase activity for the Wee kinase family.

My research work focuses on Saccharomyces jurei yeast, performing molecular alterations on the wet-lab side to support diverse species hybridization. I induce promoter alterations to improve recombination, and thereby, the viability of interspecific progeny. Using CRISPR-cas9 genome editing and DNA insertion procedures, I switch promoters in Saccharomyces jurei to bypass the yeast’s inability to recombine. The goal is that these changes allow S. jurei to successfully recombine with other Saccharomyces species and form viable spores in the progeny. These spores will then be separated and used for genetic mapping.

My current research is focused on interspecific hybridization between different Saccharomyces species to study how genetic divergences contribute to phenotypic trait differences. Even though these species diverged millions of years ago, they can still form hybrids which makes them a valuable tool for examining genetic interactions across species boundaries. However, these hybrids are often not viable due to incorrect activation of the mismatch repair (MMR) system during meiosis, which interferes with proper recombination. To address this, we are using CRISPR-based genome engineering to replace promoters of key MMR genes in multiple Saccharyomyces species, including Saccharomyces mikatae, the species I primarily work with. I am planning to generate genome edits to reduce MMR activity during meiosis and construct viable interspecific hybrids and construct interspecific hybrids. I will then assess meiotic outcomes by dissecting yeast tetrads under a microscope to measure spore viability and analyze recombination patterns.

There have been numerous experiments estimating cis-and trans-regulatory differences among organisms by hybridizing two related species and measuring allele-specific expression in the offspring. These studies have been conducted on many species, like fruit flies, chickens, and potatoes, but the data from these studies has never been compiled, organized, and used in conjunction to come to a single conclusion. My current work involves going through these studies, using RNA-seq analysis on the sequence data and organizing them together.