- Stanford University, Stanford, CA, U.S., Research Fellow in Stem Cells and Biomaterials, 2007-2012.
- University of Pennsylvania, Philadelphia, PA, U.S., PhD in Cell and Molecular Biology, 2001-2006.
- Haverford College, Haverford, PA, U.S., BSc in Cell and Molecular Biology, 1995-1999.
- Institute of Biomaterials and Biomedical Engineering, University of Toronto.
- Department of Biochemistry, University of Toronto.
- Ontario Institute for Regenerative Medicine (OIRM).
- CIHR Training Program in Regenerative Medicine.
MY RESEARCH OVERVIEW (GO TO SCIENTIFIC OVERVIEW)
Muscle stem cell bioengineering laboratory
Ah, the marvel of movement! Your skeletal muscle tissue is absolutely essential to your mobility, and your ability to breath, to swallow, or to blink. Each instance your brain decides its time to move, a signal is sent via your motor neurons to the neuromuscular junction where a burst of acetylcholine is released. This in turn actives a cascade of calcium within each skeletal muscle fibre invoking tiny molecular motors to crawl along cords of actin protein to produce a coordinated contraction of your limb muscle. As if this weren’t enough, when skeletal muscle is injured, resident adult stem cells are called to action to restore form and function.
As we age, our ability to regenerate skeletal muscle declines and the tissue succumbs to atrophy. Loss of skeletal muscle mass and function also occurs as a result of certain genetic conditions, inactivity and diseases like cancer. The goal of our research is to restore muscle function in these diverse disease settings by harnessing the potential of skeletal muscle- and induced pluripotent stem cell-derived muscle stem cells.
To achieve our goal, we employ tools and materials developed by our engineering colleagues to understand molecular mechanisms underlying muscle stem cell niche regulation and to establish three-dimensional culture models of normal and diseased skeletal muscle. Ultimately, our research program aims to identify small molecule compounds that can augment muscle stem cell regenerative potential that will then be tested in our culture models to deliver personalized medicine.
Successful achievement of our lofty goals is enabled by our placement within the Donnelly Centre. Our laboratory space is shared with geneticists (Krause and Maxwell labs) and material scientists (Shoichet lab), while being only a stones throw away from experts from a wide range of disciplines. Ultimately, success is limited only by creativity.
SCIENTIFIC RESEARCH OVERVIEW
Current projects in the lab include:
1. Muscle stem cell mechanobiology
Muscle stem cells, or ‘satellite cells’, are a rare population of cells in skeletal muscle tissue that sit on top of the long muscle fibers and beneath a blanket of proteins in their ‘niche’. For the most part, muscle stem cells are inactive, or ‘quiescent’, until they are called to action in response to tissue injury. It’s rather counterintuitive that a population of cells can remain quiescent in such a metabolically and mechanically active tissue like muscle!
We love to think about how physical features of the niche like tissue softness, topography, interstitial flow, or tensile strain influence satellite cell gene expression and their decision to remain quiescent or to divide and make more copies of themselves (self-renewal). Since these physical features change dynamically during regeneration and are altered in the course of aging and disease, our research program is poised to provide a unique picture of the biomechanical basis of skeletal muscle health and degeneration and identify novel therapeutic avenues to restore muscle strength.
2. Three-dimensional skeletal muscle models
Skeletal muscle is organized into a beautiful three-dimensional tissue. When the organization is disrupted, by injury or by other means, resident muscle stem cells are called to action to repair the damage and restore three-dimensional order. Using a histological approach on transgenic animal models, researchers capture a snap shot of the events that occur during tissue repair and the genes that mediate each stage. However, to date no one has ever watched skeletal muscle regeneration in real time, so our understanding of the process is really quite limited. To overcome this challenge, we develop and characterize three-dimensional models of normal, injured and diseased skeletal muscle tissue. In addition to establishing unique platforms to expand fundamental knowledge of muscle stem cell-mediated skeletal muscle regeneration or to support small molecule compound screens, we hope one day to make engineered replacement skeletal muscle a translational reality.
- Biomechanical Origins of Muscle Stem Cell Signal Transduction. Morrissey JB, Cheng RY, Davoudi S, Gilbert PM. J Mol Biol. 2015 May 21.
- Rejuvenation of the muscle stem cell population restores strength to injured aged muscles. Cosgrove BD, Gilbert PM, Porpiglia E, Mourkioti F, Lee SP, Corbel SY, Llewellyn ME, Delp SL, Blau HM. Nat Med. 2014 Mar;20(3):255-64.
- Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Gilbert PM, Havenstrite KL, Magnusson KE, Sacco A, Leonardi NA, Kraft P, Nguyen NK, Thrun S, Lutolf MP, Blau HM. Science. 2010 Aug 27;329(5995):1078-81.
View Pubmed search of Dr. Gilbert's full list of publications.