Image of Moreland, Robert

Robert Moreland, PhD

Professor

  • Department:Pharmacology & Physiology
  • Education: PhD, Medical College of Virginia, Richmond, Va.
Research

Dr. Moreland's group is involved in determining how smooth muscle function is regulated. They are currently examining the regulation of vascular and urinary bladder smooth muscle. This work can be divided into three complementary areas of study: signal transduction, modulation of contraction, and pathophysiology.

Smooth muscle contraction is believed to be initiated by a cascade of events beginning with stimulation-induced increases in cellular calcium and ending with phosphorylation of a protein called the myosin light chain. Dr. Moreland's signal transduction studies have centered on the roles of various isoforms of kinases and phosphatases and how they initiate or modulate contraction by effects on myosin or actin binding proteins. The lab's experiments are designed to quantitatively determine the magnitude of kinase catalyzed phosphorylation of specific cellular substrates and the role of this phosphorylation in cellular function. They are also investigating how receptor and G-protein activation alters the calcium sensitivity of the contractile filaments and if either protein kinase C, MAP kinase or Rho kinase are involved. The long-term goal is to determine the precise steps involved in the coupling of cellular excitation and contraction and to determine the precise steps of modulatory pathways that alter the contractile response to excitation. 

Dr. Moreland's work on modulation of contraction is focused on determining if thin filament proteins and specifically caldesmon are important in the development and maintenance of force. To pursue this goal, the lab uses intact and permeabilized (a technique that allows us to control the intracellular environment) strips of smooth muscle to measure force of contraction and velocity of shortening (index of crossbridge cycling rates) as well as biochemical analysis of enzyme activities and protein phosphorylation levels. In addition, they use antisense oligonucleotides and siRNA techniques to "knock-down" specific proteins within a physiologically viable tissue to determine the role that protein plays in regulation. 

Smooth muscle is the final common pathway for many diseases. Therefore a complete understanding of how smooth muscle changes during the genesis and maintenance of a disease is an important step towards the development of novel therapeutic approaches. The Moreland lab is currently involved in studies in collaboration with the Division of Urology of the University of Pennsylvania Perelman School of Medicine aimed at understanding how urinary bladder smooth muscle cells are altered following partial bladder outlet obstruction modeling that which occurs during benign prostatic hyperplasia. They are also investigating the mechanisms responsible for the changes that occur in urinary bladder smooth muscle resulting in diabetic bladder dysfunction using an animal model of Type II diabetes. Diabetic bladder dysfunction is one of the primary quality of life issues diabetic patients experience and, as such, is a current emphasis of the National Institutes of Diabetes, Digestive, and Kidney Disease. In terms of vascular smooth muscle, vascular tone is a primary determinant of total peripheral resistance and therefore arterial blood pressure. The lab has recently demonstrated that thin filament-associated proteins in vascular smooth muscle have a major role in regulating the magnitude of vascular tone. They are initiating studies to determine if changes in the regulation of these proteins may be responsible, in part, for the elevation of vascular tone and therefore arterial blood pressure in the hypertensive state.

Publications

Selected references:

"Effects of ovariectomy and 17-β estradiol replacement on molecular and functional characteristics of the rodent vaginal muscularis"
Basha ME, Chang S, Burrows L, Wein A, Moreland RS, and Chacko SK
J. Sex. Med., in press.

"Phorbol 12, 13-dibutyrate-induced, protein kinase C-mediated contraction of rabbit bladder smooth muscle"
Wang TC, Kendig DM, Trappanese DM, Smolock EM, and Moreland RS
Frontiers in Pharmacol.: Cardiovasc. Smooth Muscle Pharmacol. 2: 1-12, 2012 (Frontiers Article Alert).

"Highly regioselective synthesis of N-3 organophosphorous derivatives of 3,4-dihydropyrimidin-2(1H)-ones and their calcium channel binding studies"
Singh K, Singh K, Trappanese, DM, and Moreland RS
Eur. J Med. Chem. 54: 397-402, 2012.

"Bladder smooth muscle organ culture preparation maintains the contractile phenotype"
Wang TC, Kendig DM, Chang S, Trappanese DN, Chacko S, and Moreland RS
Am. J. Physiol. Renal Physiol. 303: F1382-F1397, 2012.

"Functional and molecular consequences of ionizing irradiation on large conductance Ca2+ activated K+ channels in rat aorta smooth muscle cells
Soloviev A, Tishki, S, Ivanova I, Zelensky S, Dosenko V, Kyrychenko S, and Moreland RS
Life Sci. 84: 164-171, 2009.

"siRNA mediated knock down of h-caldesmon in vascular smooth muscle"
Smolock EM, Trappanese DM, Chang S, Wang TC, Titchenell P, and Moreland RS
Am. J. Physiol. Heart Circ. Physiol. 297: H1930-H1939, 2009.

"Roles of protein kinase C and Rho kinase in carbachol induced contraction of rabbit bladder smooth muscle"
Wang TC, Kendig DM, Smolock EM, and Moreland RS
Am. J. Physiol. Renal Physiol. 297: F1534-F1542, 2009.

"Unaided addition of carbon nucleophiles to pyrimidinones. An efficacious protocol for C-4 substituted 3,4-dihydropyrimidinones. Synthesis and calcium channel binding studies"
Singh K, Arora D, Falkowski D, Liu Q, and Moreland RS
Eur. J. Org. Chem. 3258-3264, 2009.

Dr. Moreland is a professor in the Department of Pharmacology & Physiology at Drexel University College of Medicine.

Research Location

Department of Pharmacology & Physiology
245 North 15th Street
Mail Stop #488
Philadelphia, PA 19102
Phone: 215-762-5133
Fax: 215-762-2299

Additional Information

Location:
New College Building, Rm. 8174

Email Dr. Moreland

Related Pages

Pharmacology & Physiology

Biomedical Graduate Studies

Professional Studies in the Health Sciences

You are leaving the Drexel University College of Medicine website

By clicking on this link, you will be leaving the Drexel University College of Medicine–maintained website and entering another website that is not owned, operated, or controlled by Drexel University College of Medicine.

By linking to this external website, Drexel University College of Medicine does not endorse or verify the external website’s content, opinions, products, services, or privacy or security policies.