Probiotic yeast Saccharomyces boulardii synthetic biotic to deliver therapeutic biologics to treat gastrointestinal (GI) disease and disease influenced by the GI tract
(a collaborative project with Dr. Mike Tyers of SickKids Research Institute)
Mucosa-derived polyamines, especially putrescine and spermidine, are essential for intestinal tissue remodeling during weaning and promote mucosal regeneration following gut injuries in rats (Luk et al. 1980. Science 210:195). To harness the potential of polyamines in tissue repair and regeneration as a therapeutic for inflammatory bowel disease (IBD), we have engineered the probiotic yeast Saccharomyces boulardii (Sb) to overexpress and secrete spermidine. The spermidine-secreting Sb strain, called Sb576, synthesizes and secretes spermidine in the GI tract and ameliorates colitis and colitis-associated colon cancer in mice (Mohaqiq et al. 2025. Scientific Reports. https://doi.org/10.1038/s41598-025-16736-5). We are currently developing Sb strains secreting a combination of the pro-regenerative spermidine and protein biologics that target key inflammatory pathways in IBD. These combinatorial Sb strains might have the potential to break treatment ceiling by current biologics therapies in IBD.
As a proof of principle, we have also demonstrated that food supplementation of live Sb576, but not free spermidine, reduces, and partially rescues, aging-associated learning and memory decline in Drosophila melanogaster, likely through a gut-brain axis mechanism (Parweez et al. Frontiers in Neuroscience Volume 19 - 2025 | https://doi.org/10.3389/fnins.2025.1628160). Our long-term goal is to develop S boulardii synthetic biotic as therapeutics for neurodegenerative diseases.

A pill for advanced maternal-age infertility?
Infertility has become an increasing social and medical issue as women delay childbearing in modern society. Declining egg quality is the most important factor in these reproductive difficulties. Our recent discovery offers a promising solution. We have identified putrescine deficiency as a major cause of poor egg quality in aged mice. Putrescine is a biogenic polyamine naturally produced in peri-ovulatory ovaries in all animal species studied thus far. Peri-ovulatory putrescine supplementation in drinking water reduces miscarriage and increases live births in aged mice. If similar strategy proves effective in women, peri-ovulatory putrescine supplementation may be the magic pill for millions of older women (i.e. 35 yrs. and older) pursuing healthy pregnancy.

Discovering the secret of cell division in the giant frog eggs
We have a longstanding interest in discovering the mechanisms of polar body formation during animal oocyte maturation, using Xenopus frogs as a model. Unlike a typical cell division producing two identical daughter cells, oocyte maturation produces a miniature, non-viable polar body and a mature egg. Polar body formation serves to halve chromosome number while preserving all nutrients in the mature egg. This is especially important for the frog since the egg provides all nutritional needs of post-fertilization embryonic development until the tadpole stage. The giant frog eggs offer unparalleled technical advantages for the many fundamental discoveries, by others and by us. These discoveries provide insight into how cell builds a bipolar spindle, what determines spindle positioning within the cell to ensure maximum retention of nutrients in the eggs, and how the spindle align chromosomes properly to ensure expelling exactly half of the chromosomes (in polar body) to prevent aneuploidy. Aneuploidy, or chromosome error, invariably results in early embryo demise or severe birth defects (e.g. Down syndrome).