McMaster University

McMaster University

Background

Faculty

Thomas Hawke

Thomas Hawke, PhD

Associate Member
Associate Professor, Pathology

HSC 4N65
McMaster University
905-525-9140 ext. 22372

hawke@mcmaster.ca

Visit Thomas Hawke's webpage

Research

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 not needed.

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 be realized.

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.

Diabetic Myopathy

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).

 

Selected Publications

  • 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. 2010 May;298(5):C1100-8.
  • 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.

 

 

 

 

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