The metabolome plays a vital role in cellular processes by supplying the building blocks for macromolecule synthesis, driving energy production, and enabling growth and reproduction. In contrast to the genome, transcriptome, and proteome—which vary greatly across species—the fundamental structure and organization of metabolism remains highly conserved across all domains of life. This remarkable universality lends strong support to the metabolism-first hypothesis, which suggests that metabolic networks may have emerged before genetic information in the early stages of life on Earth.
Despite its fundamental role, metabolomic analysis presents unique challenges. The vast chemical heterogeneity of metabolites demands customized analytical approaches, as no single method can comprehensively capture all metabolite classes with equal efficiency.
Research in our laboratory is centered on two major themes:
Investigating the origins and evolutionary development of metabolic biochemistry.
Developing analytical methodologies for metabolome characterization.
Life is believed to have begun gradually, starting from simple non-living molecules through a process called abiogenesis. It is believed that some of the earliest chemical pathways involved in this process were similar to modern metabolic cycles, like the Wood-Ljungdahl pathway and the citric acid cycle (also known as the Krebs cycle). Lab experiments have shown that reactions similar to these could happen without enzymes, using simple metals found on early Earth. Over time, however, many of these metal-based reactions were taken over by small organic molecules called cofactors.
These cofactors are now essential parts of life. They help run the chemical reactions in all living things, from humans to bacteria. But one big question remains: When did these cofactors become part of life’s chemistry? Did they evolve alongside early chemical networks, or did they come later, after complex molecules like proteins or RNA appeared? And were their shapes and structures just random accidents, or were they chosen because they were especially useful or easy to make in early Earth conditions?
Interestingly, many cofactors have similar building blocks but do very different jobs. For example, folic acid (Vitamin B9) and riboflavin (Vitamin B2) both contain a part called an aminopyrimidine, but folic acid helps carry small carbon groups, while riboflavin is involved in energy transfer. Similarly, pyridoxal phosphate (Vitamin B6) and nicotinamide (Vitamin B3) both share a structure called pyridine, yet they take part in very different types of reactions.
By studying how these molecules might have evolved and why they became so important, we hope to better understand how life’s chemistry was built. Was it because they were easy to form on early Earth? Or were they just so useful that they became essential parts of life? These are the questions our research aims to answer, in hopes of uncovering how life took its first steps toward the complex biology we see today.
The metabolome, representing one of the most proximal omic layers to phenotype, offers direct insights into an organism’s physiological state and biochemical activity. However, comprehensive metabolomic analysis is inherently challenging due to the vast chemical diversity of metabolites, their dynamic concentration ranges, and the complexity of their biological origins. These factors necessitate analytical techniques with high sensitivity, specificity, and adaptability.
Our laboratory is focused on developing both qualitative and quantitative workflows for metabolome characterization using liquid chromatography–mass spectrometry (LC-MS) and gas chromatography–mass spectrometry (GC-MS). These platforms enable the deconvolution of complex biological matrices, facilitating accurate detection and identification of metabolites. We employ strategies such as spectral matching against curated reference libraries and fragmentation-based structure elucidation guided by established principles of organic chemistry to enhance metabolite identification confidence.
In parallel, we are working on establishing high-throughput MS-based analytical pipelines to enable large-scale metabolomic profiling. Downstream computational analysis will focus on extracting biologically meaningful information, including the identification of metabolic signatures and biomarkers associated with distinct physiological or pathological states.