Associate Professor, Pathology
905-525-9140 ext. 22372
Visit Thomas Hawke's webpage
Dr. Hawke’s research focus is on the role and regulation of muscle satellite
cells, the stem cell population of skeletal muscle, in health and disease states
such as diabetes mellitus and limb girdle muscular dystrophy.
Skeletal muscle has an amazing capacity to regenerate following injury. The
injury may be induced by a number of factors including heavy exercise, trauma or
disease. The regenerative capacity of skeletal muscle is due primarily to a rare
population of progenitor cells called muscle satellite cells. These cells have
many characteristics of stem cells, including the capacity divide numerous
times, self-renew their population and enter a state of quiescence when they are
The potential of this cell population is tremendous, however, the use of
these cells for cell transplantation into patients with myopathies has yielded
disappointing results. This is mostly due to a lack of knowledge regarding the
regulatory mechanisms controlling these cells. It is only through a more
thorough understanding of this cell population that their therapeutic potential
Using molecular, cellular and physiological techniques, we are attempting to
define the regulation of this cell population in health and disease.Techniques
used in the lab include: histology, immunohistochemistry, protein and RNA
expression assays, isolated single fibre and primary myoblast cultures, in situ
muscle stimulation to assess contractile function, adenoviral mediated
overexpression and/or silencing and metabolic enzyme assays.
Currently, Dr. Hawke has two major research project focuses:
Role of Xin in the Muscular Dystrophies
Xin (Cmya-1; cardiomyopathy-associated-1) is an adapter protein containing
novel actin-binding repeats. The current literature suggests that Xin is
involved in the remodeling of the actin cytoskeleton of striated muscles during
sarcomere assembly and cardiac morphogenesis, though its exact role is not well
understood. Our previous investigations into the molecular regulation of
skeletal muscle regeneration led to the finding that the expression Cmya1, the
gene encoding Xin, was significantly upregulated during the early phases of
skeletal muscle regeneration. Our currents studies into Xin are investigating
its function in skeletal muscle regeneration and the effects of modulating Xin
expression levels during the regenerative process.
Insulin-dependent diabetes mellitus (T1DM) is typified by an autoimmune
mediated destruction of the pancreatic B-cells. Over time, T1DM progresses to a
significant decrease, or even complete abolishment, of pancreatic B-cell mass,
rendering the patient in a state of hypoinsulinemia and hyperglycemia. A host of
complications are associated with T1DM, including retinopathy, nephropathy,
neuropathy, and myopathy. Our current understanding of the etiology and effects
of diabetes on skeletal muscle growth and repair is very limited and the studies
available have utilized pharmacologically-induced diabetic rodent models. The
use of these models jeopardizes the strength of the data obtained, as the drugs
used to induce B-cell death are also capable of impairing satellite cell
function. We are currently investigating the effects of short- and long-term
diabetes on skeletal muscle growth and repair in more appropriate animal models
(e.g. Akita mouse).
- Inhibition of plasminogen activator inhibitor-1 (PAI-1) restores skeletal
muscle regeneration in untreated type 1 diabetic mice. Krause MP, Moradi J,
Nissar A, Riddell MC, Hawke TJ. Diabetes- Accepted April 7, 2011.
- Volume regulation in mammalian skeletal muscle: The role of
sodium-potassium-chloride cotransporters (NKCC) during exposure to hypertonic
solutions. Lindinger MI, Leung M, Trajcevski KE, Hawke TJ. J. Physiol.
Accepted April 7, 2011.
- Impaired Growth and Force Production in Skeletal Muscles of Young Partially
Pancreatectomized Rats: a Model of Adolescent Type 1 Diabetic Myopathy. Gordon
CS, Serino AS, Krause MP, Campbell J, Cafarelli E, Adegoke OAJ, Hawke TJ,
Riddell MC. PLoS One. 2010 Nov 17;5(11):e14032. cites=0
- Effects of Type 1 Diabetes Mellitus on Skeletal Muscle: Clinical
Observations and Physiological Mechanisms. Krause MP, Riddell, MC, Hawke
TJ. Pediatr Diabetes. 2010 Sep 22. doi:
10.1111/j.1399-5448.2010.00699.x PMID: 20860561
- Silencing of Mustn1 inhibits myogenic fusion and differentiation. Liu C,
Gersch RP, Hawke TJ, Hadjiargyrou M. Am J Physiol Cell Physiol.
- Muscle-specific adaptations, impaired oxidative capacity and maintenance of
contractile function characterize diet-induced obese mouse skeletal muscle.
Shortreed KE, Krause MP, Huang JH, Dhanani D, Moradi J, Ceddia RB, Hawke
TJ. PLoS One. 2009 Oct 6;4(10):e7293.