Two ISCRM faculty members, Andrea Wills, PhD, Assistant Professor, Biochemistry and Daniel Yang, MD, Assistant Professor, Medicine/Cardiology, have received prestigious awards from the John H. Tietze Foundation Trust that will help fuel promising research underway in their labs.
Dystrophy syndromes and other muscle-wasting disorders rob otherwise young, healthy people of their quality of life. A major therapeutic goal is to restore skeletal muscle mass and function in these patients, either by helping injured muscles to heal, or through interventions such as gene therapy and muscle cell engraftment.
However, a persistent challenge in muscle regeneration is that many differentiation protocols rely on recapitulating how muscle development happens during embryonic development, when in fact regeneration may progress through a different regulatory path. To better understand this question, ISCRM faculty member Andrea Wills is looking closely at a frog, known as Xenopus tropicalis, that is able to fully regrow its limbs and tail as a tadpole, including the muscles of these appendages.
The John H. Tietze Stem Cell Scientist Award will support Dr. Wills’ effort to discover the molecular and cellular mechanisms that underlie seamless muscle regeneration in these two frog structures, which use quite different mechanisms of muscle development. She and her team will use single-cell sequencing to trace the trajectories of gene expression and gene regulation that different populations of muscle progenitor cells undergo as they progress through regeneration to fully differentiated muscle.
“Our expectation is that by defining how muscle regeneration progresses in the complete context of a whole animal, we will learn new strategies for muscle differentiation in vitro that will help make therapeutic strategies like engraftment more successful, and also new strategies to directly promote repair,” says Wills. “We are excited to be a part of the ISCRM community, grateful to the Tietze Foundation, and excited to translate what we learn in naturally occurring regeneration to human cells and eventually to patients.”
Arrhythmogenic cardiomyopathy is a devastating inheritable heart disease characterized by abnormal heart rhythms and a weakened heart. This life-threatening condition is estimated to affect 1 in 5,000 individuals in the general population.
Mutations in desmoplakin, a structural protein that helps tether heart cells to their neighbors, are common causes of arrhythmogenic cardiomyopathy, but the mechanism by which these mutations cause heart disease is unknown. ISCRM faculty member Daniel Yang hypothesizes that these mutations, which often cause an abnormally shortened desmoplakin gene, result in a loss of functional desmoplakin protein (haploinsufficiency) and that restoring normal levels of full-length desmoplakin protein would lead to better patient outcomes.
The Jaconette L. Tietze Young Scientist Award will allow Yang and his lab to test these hypotheses in human 3D engineered heart tissues generated from stem cells derived from patients with desmoplakin-associated arrhythmogenic cardiomyopathy. Yang anticipates that this “disease in a dish” model coupled with cutting-edge gene-editing techniques will allow us to dissect the mechanisms by which these desmoplakin mutations cause disease and thereby inform us on potential novel disease-modifying strategies for these patients.
“I’m flattered and truly honored to be recognized by ISCRM with the Jaconette L. Tietze Young Scientist Award,” says Yang. “My lab and I are very grateful for this support and the ability to be part of this wonderful scientific community. We hope this award will help accelerate our research so that we can make a positive impact for patients with heart disease.”
John H. Tietze Stem Cell Scientist Award
The John H. Tietze Stem Cell Scientist Award is a one-year award of $50,000 to support the research of any UW FACULTY member of ISCRM who is pursuing novel preliminary experiments, where the grant might provide sufficient stimulus to enable the research to advance to the point of being competitive for external funding. The research should involve or be relevant to some aspect of stem or progenitor cell biology or therapies.
Jaconette L. Tietze Young Scientist Award
The Jaconette L. Tietze Young Scientist Award is also for one year of support of $25,000. Preference will be given a junior faculty (including Acting Instructor level) located at the UW who has not yet received major external funding (such as an R01). The research should involve or be relevant to some aspect of stem or progenitor cell biology or therapies.