Lipid Metabolism by Cytochrome P450s 

Welcome to Das Lab at Georgia Tech !! 

Research Directions – Das Laboratory at Georgia Tech

Our laboratory investigates the chemistry of lipid metabolism with an emphasis on the fundamental mechanisms by which lipids and small molecules interact with proteins. By integrating biochemical, biophysical, and analytical approaches, we aim to advance our understanding of key processes in immunology, neuroscience, and cellular regulation. Our research program is organized around three major directions:

1. Mechanistic Studies of Lipid Biotransformation by Enzymes

We explore the fundamental chemistry of how enzymes—particularly cytochrome P450s—transform lipids into bioactive metabolites. Our focus includes a wide array of small molecules such as endogenous lipids, exogenous dietary lipids, phytocannabinoids, and therapeutic drugs. Using a suite of analytical techniques including spectroscopy, mass spectrometry, microscopy, and nanodisc technology, we elucidate the molecular basis of lipid-protein interactions and catalytic mechanisms. We are particularly interested in how these small molecules modulate the activity of receptors, ion channels, and metabolic enzymes, shaping both physiological and pathological responses.

2. Endocannabinoid Metabolism and Signaling

One of our central research areas involves the metabolism and function of endocannabinoids—lipid mediators with emerging significance in pain, inflammation, and neurobiology. We study their biosynthesis and catabolism by metalloenzymes, including P450s, and investigate how their interactions with receptors such as CB1, CB2, and TRP channels regulate signaling pathways. Our goal is to uncover new insights into the molecular pharmacology of endocannabinoids and their roles in conditions such as addiction, aging, neurodegeneration, and immune regulation.

3. Minor Cannabinoid Metabolism and Immunomodulation

Minor cannabinoids like cannabigerol (CBG) and cannabichromene (CBC) are gaining attention for their non-psychoactive therapeutic potential, particularly in pain relief and neuroprotection. Our lab studies the metabolism of these compounds by cytochrome P450 enzymes in both liver and brain. Using targeted LC-MS/MS analysis and synthesized authentic standards, we have identified key oxidative metabolites—including epoxides and hydroxylated products—and demonstrated that their formation is isoform-dependent and deviates from classic Michaelis-Menten kinetics. Complementary computational studies (molecular dynamics) reveal how cannabinoid orientation within the P450 heme pocket influences site-selectivity and metabolic outcome. Importantly, we find that these metabolites exhibit immunomodulatory properties, decreasing pro-inflammatory cytokine expression while enhancing anti-inflammatory responses. This work opens new avenues for identifying bioactive metabolites with therapeutic potential.

Our Broad Philosophy

Our laboratory is grounded in the belief that academic research serves three equally vital purposes: advancing scientific knowledge, uncovering fundamental principles, and cultivating the next generation of scientists. Together, these objectives drive the growth and continuity of knowledge, ultimately benefiting the broader community.

Our Mentorship and Training Philosophy

The path from novice to expert in scientific research is complex and multidimensional. As a collaborative team, we are committed to guiding our students and trainees through this journey with clarity and support. Transparent communication and a culture of openness are essential to building strong mentor-mentee relationships. We strive to make the research experience both meaningful and enjoyable, ensuring that it is as productive as it is enriching.