Research

A million nematode (roundworm) species are estimated to inhabit the earth, they are found in virtually every type of environment, and they include many parasitic species, which infect over 1 billion people worldwide and cause hundreds of billions of dollars in agricultural damage.  The focus of our research group is to identify and characterize the chemical structures of nematode signaling molecules and to investigate the biosynthesis and mechanism of action of these molecules.  We employ a multidisciplinary approach, including genome editing, metabolomics, synthetic chemistry, biochemistry, and structural biology.  Our results have provided new insights into how nematodes use small molecules to control their lifecycles and will enable the development of novel strategies to target the lifecycles of parasitic nematodes. 

Discovery and biosynthesis of the chemical language of nematodes.   Our group has identified many of the ascaroside pheromones that nematodes secrete to coordinate their development and behavior (Bhar, in Comprehensive Natural Products III, 2020).  We have shown that nematodes produce these signaling molecules by first shortening the ascaroside side chain through peroxisomal beta-oxidation and then decorating the ascaroside core structure with a variety of modifications (Faghih, Journal of the American Chemical Society, 2020; Xu, Bioscience Reports, 2026).  Acyl-CoA oxidases (ACOXs), which catalyze the first step in beta-oxidation, act as gatekeepers for production of ascarosides with specific side-chain lengths (Bhar, ACS Chemical Biology, 2025).  We have identified a novel mechanism whereby ATP allosterically regulates the ACOXs, thereby linking ascaroside production to the worm’s metabolic status (Perez, Nature Communications, 2025).  We have also shown that acyl-CoA thioesterases terminate the beta-oxidation process and are responsible for the production of a key ascaroside component of the dauer pheromone, which triggers the stress-resistant dauer larval stage in nematodes (Bhar, Cell Chemical Biology, 2024). 

Discovery and biosynthesis of the anti-cancer nemamides and euglenatides.  Our group discovered a family of hybrid polyketide-nonribosomal peptides in nematodes, the nemamides, and showed that these metabolites are produced by a huge enzymatic assembly line (PKS-1/NRPS-1) in two neurons in the worm (Feng, Nature Communications, 2021; Gordon, ACS Chemical Biology, 2025).  The nemamides promote survival of nematodes during starvation in part through their effects on the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway.  Because the nemamides are produced in minute quantities by nematodes, we have initiated an effort to synthesize the nemamides to study their mechanism of action (Yu, Journal of Natural Products, 2025).  Furthermore, in algae, we and others have identified many euglenatides, which are structurally similar to the nemamides, but can be isolated in higher amounts, thereby enabling us to carry out more extensive biological studies (Elbanna, Natural Products and Bioprospecting, 2025).  We have shown that both the nemamides and the euglenatides have antiproliferative activity against mammalian cancer cell lines.  Our focus now is to investigate the molecular mechanism of these important signaling molecules.