Interpreting the geometry and rhythm of early kidney formation for synthetic morphogenesis
Around 10% of people develop chronic kidney disease in their lifetime, and up to a third of all birth defects affect the kidney and urinary tract. Despite this enormous clinical burden, treatment options are limited to dialysis and transplantation, which carry significant morbidity and limited scale. We are contributing a third route by learning the developmental principles by which the kidney builds itself in the embryo. These principles coincide with crucial engineering gaps around stem cell renewal vs. differentiation balance, massive parallelization of epithelial structures and their large-scale fluidic integration. We have recently uncovered geometric, mechanical, and signaling principles that drive these processes, and have coupled them to in vitro reconstitution in kidney organoids. In particular, I will discuss a new biological clock that balances nephron progenitor cell decision making in the nephron-forming niche and the role of mechanics as a component of the underlying pacemaker. Our data touch on global principles for scale-up of epithelial tissues for regenerative medicine and are relevant to similar efforts in the gut, lung, pancreas, mammary and salivary glands, etc.
Bio: Alex Hughes is an associate professor of bioengineering at the University of Pennsylvania. Originally from California and New Zealand, he graduated with a B.E./B.Sc. in chemical & materials engineering/pharmacology at the University of Auckland, NZ in 2008. He completed his graduate studies at UC Berkeley in 2013 working with Amy Herr on microfluidic and single-cell proteomics. Hughes then completed a Jane Coffin Childs postdoctoral fellowship with Zev Gartner at UC San Francisco, where he developed DNA-based cell patterning technologies to model the mechanical and cell collective basis of curvature at tissue interfaces during embryonic development.
Hughes’s research focuses on engineering organogenesis. Most recently the Hughes lab has studied the cellular, signaling, and mechanical basis of kidney development using human kidney organoids, advanced cell patterning and imaging technologies, and dynamic tissue scaffolds. Hughes’s honors and awards include a 2023 BMES-CMBE Rising Star Junior Faculty Award, 2021 NSF CAREER Award; Jane Coffin Childs, American Cancer Society and NIH F32 postdoctoral fellowships; and a Society of General Physiologists Scholarship at the Woods Hole Marine Biological Laboratory.