Dense Connective Tissues: A Journey from Myosins to Hedgehogs

Nathaniel Dyment, Ph.D.
Assistant Professor, Orthopaedic Surgery and Bioengineering
University of Pennsylvania
DCC 330
Thu, December 07, 2023 at 2:00 PM

I will tell two stories from my lab. The first story is how biophysical cues dictate the formation and maintenance of dense connective tissues. This work includes how muscle loading during embryogenesis dictates the growth of tissues in the knee joint and how cell contractility regulates cell fate and tissue homeostasis. The second story, which started with a serendipitous discovery during my graduate studies, is focused on how the hedgehog signaling pathway is a master regulator of fibrocartilage formation during enthesis development and tendon-to-bone repair in adults.

Nat Dyment, Ph.D

I obtained my undergraduate degree in Materials Science and Engineering with a specialization in Biomaterials from the University of Illinois at Urbana-Champaign in 2005. I completed my PhD in the Functional Tissue Engineering laboratory under the direction of Dr. David Butler at the University of Cincinnati in 2011. After postdoctoral training in musculoskeletal biology with Dr. David Rowe at UConn Health, I moved to the University of Pennsylvania where I developed an independent research program in the McKay Orthopaedic Research Laboratory. My lab’s primary research goals are directed towards understanding the genetic, cellular, and mechanical mechanisms that regulate normal development, disease, and repair of joint tissues. I am particularly interested in identifying markers that define resident progenitors vs. mature cell types and the environmental cues (e.g., molecular and mechanical) that regulate their differentiation. I was awarded a K99/R00 grant (AR067283) in 2015 to define the tendon cell lineage and pathways that regulate tenogenesis, which led to my first independent R01 (AR076381) to investigate the role of hedgehog in tendon-to-bone repair and an R21 (AR078429) to develop novel drug delivery systems to target the hedgehog pathway to improve repair outcomes. My lab also investigates how mechanical forces impact the formation and maintenance of dense connective tissues (e.g., R01AR075418 and P50AR080581), which have resulted in a recent publication in PNAS (PMC10235980) defining the mechanotransducive signaling that regulate tensional homeostasis. The long-term goals of my lab are directed towards translating these mechanistic studies to novel therapeutic strategies.