• Elucidation of the mechanism of smooth muscle contraction at tissue and cellular level using ultrastructural, biophysical, biochrmical and molecular biological approaches.
• Elucidation of the pathogenesis of the changes in the contractility of 'asthmatic' airway smooth muscle using the approaches just cited.
• Study of the pathogenesis of persistent pulmonary hypertension of the new born at vascular level.
  Approaches:
  1. Electronic muscle lever system studies of smooth muscle cross bridge contractility
  2. Immunocytochemical (including flow cytometry) and electron microscopic study of smooth muscle structure at cellular level
  3. Biochemical and biophysical techniques - SDS-PAGE, Western, Northern and Southern blots, GFP studies, dominant negative receptor construct studies, and yeast 2-hybrid assays.

The main focus is on elucidation of mechanisms of contraction at subcellular level. Using high performance electromagnetic muscle lever systems we have characterized the nature of actomyosin cross-bridges responsible for muscle contraction - this represents a new development in the field. We are conducting studies to determine the changes in mechanical properties of airway smooth muscle that occur in asthma.

Our biochemical studies of the proteins regulating the muscle's contractile proteins are based on 1- and 2-dimensional gel electrophoresis, Western blotting and the Fura-2 technique. Studies using flash photolysis of caged compounds (ATP, Ca2+, IP3, EGTA) are also underway. They are designed to elucidate the mechanism for cross-bridge cycling; they should also aid in determining what alterations occur in asthma and high blood pressure. As current work indicates that alteration in smooth muscle myosin light chain total kinase activity develops in sensitized muscle, studies of gene expression and translation of this enzyme have been initiated. Airway smooth muscle culture studies are being conducted to elucidate mechanisms underlying the smooth muscle hypertrophy and hyperplasia of chronic asthma. Single airway smooth muscle contractility is being studied using a high resolution length and force transducer.

• M.B.B.S. Univ. of Lucknow, India, 1950
• M.D. Univ. of Lucknow, India, 1953
• F.R.C.P. / F.R.S.M. (London, England)
• Assistant Professor (Physiology), Univ. of Manitoba, 1966-70
• Associate Professor (Physiology), Univ. of Manitoba, 1971-73
• Program Director, Smooth Muscle Research, Univ. of Manitoba, 1989-2011
• Professor (Physiology), Univ. of Manitoba, 1973-2011
• Senior Scholar (Physiology) Univ of Manitoba, 2011 - present