Overall Research Theme
Our research group integrates comparative genomics and computational structural biology to investigate fundamental questions across the biological spectrum. We leverage a broad suite of computational approaches to explore diverse biological systems, with a core focus on evolutionary logic and inference. Guided by the principle that evolutionary thinking offers a powerful lens to decode molecular diversity and innovation, our work builds on the basis that nature—through billions of genetic experiments over evolutionary time—has woven, and continues to weave, a dynamic tapestry of molecular evolution. Comparative and evolutionary genomics provide the means to unravel the dynamic landscape of molecular evolution and reveal the principles—such as divergence, constraint, convergence, and related forces—that drive molecular innovation and functional diversification. At the molecular scale, we analyze sequence–structure relationships of protein domains and families, track lineage-specific gene expansions, and identify diversification patterns that scale up to organismal adaptation and evolutionary novelty. These approaches allow us to dissect the molecular strategies from prokaryotic defenses against selfish genetic elements to major eukaryotic transitions shaped by gene family expansions and whole-genome duplications. We are also broadly interested in the evolution of protein folds, focusing on how the evolutionary malleability of folds enables proteins to adapt, diversify, and repurpose their functions across diverse biological contexts—and how these functional shifts can be systematically traced and predicted using computational approaches.
Unified by a central interest in the evolution of molecular systems, our research themes apply evolutionary reasoning to understand how proteins and genomes diversify, adapt, and innovate across biological contexts. The following sections highlight the major research themes currently pursued in our group :-
Specific Research Themes
Prokaryotic Defense Systems
Our research focuses on the discovery, classification, and evolutionary dynamics of prokaryotic immune systems that protect against invasive genetic elements such as bacteriophages, conjugative plasmids, and transposons. Despite their molecular diversity, these systems often share a conserved functional architecture comprising four major components:
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sensors that recognize foreign genetic material;
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modules that discriminate self from non-self;
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effectors that neutralize or inhibit the invader; and
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regulatory elements that control the timing and magnitude of the response.
Within this framework, we have redefined the architecture of the Dnd system and identified a novel defense module dependent on the HerA/FtsK ATPase—a mechanism with no known precedent. In parallel, we are expanding our investigations to a range of newly discovered or poorly characterized systems, as well as several novel candidates identified through large-scale comparative genomics. To elucidate their functional roles, we examine conserved gene neighborhoods, domain architectures, and patterns of co-occurrence—approaches that shed light on how these systems are organized, deployed, and integrated into broader cellular defense strategies.
Lineage-Specific Expansions of Gene Families
On the eukaryotic side, we are broadly interested in the role of lineage-specific expansions (LSEs) as a major driver of genomic innovation and biological diversification. LSEs generate raw material for evolutionary novelty, contributing to lineage-defining traits such as chemosensory repertoires, signaling complexity, and a range of ecological and behavioral adaptations. Our current work centers on the evolutionary dynamics of chemosensory systems and the expansion of gene families involved in environmental sensing and response. We analyze patterns of gene family expansion and diversification across a broad taxonomic range, including several newly sequenced invertebrate genomes. By integrating comparative genomics, gene family modeling, domain architecture analysis, and structural prediction, we reconstruct the evolutionary history and functional divergence of these expanded families—aiming to uncover how LSEs give rise to novel molecular functions, enable lineage-specific adaptations, and shape the broader functional landscape of animal genomes.
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Genome Sequencing of Invertebrates to Study the LSEs and Other Adaptive Diversifications
To support these investigations on diverse LSEs, we are also actively engaged in generating high-quality genomic resources for molluscs, a diverse and evolutionarily important phylum that remains underrepresented in genomic databases. Molluscs exhibit extraordinary diversity in body plans, ecologies, and physiological traits, yet comprehensive genomic frameworks are lacking for many lineages. As part of our ongoing efforts, we have sequenced and assembled the genomes of two ecologically distinct gastropods: Melo melo (a large benthic predator from the Volutidae family) and Telescopium telescopium (a detritivorous intertidal gastropod from the Potamididae family). These represent the first reference genomes for their respective families, filling critical phylogenetic and ecological gaps. Our assemblies provide a foundation for exploring lineage-specific expansions, sensory and immune gene repertoires, and adaptations to distinct trophic and habitat strategies. For instance, Melo melo shows marked expansions in detoxification, immune, and signaling gene families likely linked to its predatory lifestyle, while T. telescopium exhibits genomic signatures associated with intertidal stress and sediment-based feeding. These genomic resources not only support our investigations into molluscan chemosensation and lineage-specific adaptation but also contribute broadly to the study of spiralian evolution, biomineralization, and novel gene family innovation in lophotrochozoans
Comparative Genomics of Lipid-Binding GPCRs: Evolution, Specificity, and Human Variation
We extend our evolutionary framework to proteins with drug target potential, using comparative and structural genomics to uncover hidden diversity, functional innovation, and pharmacological relevance. As precision medicine advances, understanding how genetic variation influences drug response is more crucial than ever—particularly in overlooked receptor families with untapped therapeutic potential. A key focus of the lab is on the evolution and pharmacogenomics of lipid-binding G protein-coupled receptors (GPCRs), a diverse yet a relatively understudied subset of Class-A GPCRs. While aminergic and peptide-binding receptors dominate the landscape of current drug targets, lipid-binding GPCRs—responsive to ligands such as prostaglandins, endocannabinoids, and fatty acids—remain significantly underrepresented, despite their central roles in immunity, metabolism, and neurophysiology. Unlocking the evolutionary logic of these receptors may be key to identifying new drug targets and explaining why treatments work differently across individuals. We aim to uncover when and where different receptor subtypes emerged, whether hidden or misannotated subtypes exist, and how convergent and divergent evolutionary processes have shaped their diversification. Using comparative genomics and phylogenetics, we reconstruct the evolutionary trajectories of lipid-binding GPCRs across metazoans. A key focus is the ligand-binding groove of these 7-transmembrane receptors, where we identify conserved structural features that have been maintained over deep evolutionary time—offering insights into both the constraints and innovations that define ligand specificity. We then leverage this evolutionary perspective to analyze residue-level variation in human populations, using pharmacogenomic and population-scale datasets to examine how natural genetic differences—particularly in and around evolutionarily conserved binding sites—may influence receptor function and drug response. This integrated approach—linking deep evolutionary history with modern pharmacological variation—offers a powerful lens to understand how molecular diversity shapes function, selectivity, and therapeutic potential.