A committed academician and researcher, Dr. Stull has contributed extensive professional and academic service to his field and the university and was the holder of the Fouad A. Bashour Distinguished Chair in Physiology while he served as Chair of the Department of Physiology for 30 years. Dr. Stull's research involves the cellular and molecular basis of how contraction of muscle cells occurs in response to chemical signals from nerves and hormones. The motor protein, myosin initiates movement in all cells in the body by tracking on actin filaments. Myosin activity is enhanced by the calcium-dependent by myosin light chain kinase which phosphorylates a regulatory subunit of myosin while myosin light chain phosphatase dephosphorylates the light chain. Impaired light chain phosphorylation causes heart failure, and failed smooth muscle functions involving the hollow organs of the body (blood vessels, airways, intestines, and bladder). The phosphorylation of myosin is not a simple cascade but is controlled by different integrative signaling modules forming cellular networks with different second messenger systems.
His work is directed to understanding how kinase and phosphatase activate the myosin motor in muscle cells in relation to chemical signals controlling the networks. He has discovered two new kinases in heart muscle that may be key regulators of its myosin motor protein. One kinase, cardiac myosin light chain kinase is greatly elevated in diseased heart and thus, may be recruited to enhance myosin function to help the heart pump blood. He has established that this kinase is essential for the basal phosphorylation of myosin and maintenance of heart performance. Another newly identified kinase may be recruited to phosphorylate myosin with stresses acting on the heart during disease states.
He has also established that all smooth muscles of the body require myosin phosphorylation by a smooth muscle specific myosin light chain kinase. This phosphorylation is necessary for control of blood pressure by smooth muscle cells in blood vessels, movement of digested food in the stomach and intestines, maintenance of airways in the lungs and emptying of the urinary bladder. We have investigated interconnected chemical networks that affect myosin phosphorylation using genetically modified mice with biophysical, biochemical and physiological measurements. Primary hypotheses are directed to identifying the key signaling proteins essential for smooth muscle contraction that may contribute to the development of different smooth muscle based diseases, including our recent observation that mutations in the gene of smooth muscle myosin light chain kinase causes aortic aneurysm and dissection in humans.
- Rhodes College (1966), Biology
- Graduate School
- Emory University (1971), Pharmacology
- Cardiac Performance and Failure: Myofibrillar Protein Phosphorylation
- Signaling to Myosin in Smooth Muscles: Models of Hollow Organ Functions and Diseases
- Cardiac myosin light chain is phosphorylated by Ca2+/calmodulin-dependent and -independent kinase activities.
- Chang AN, Mahajan P, Knapp S, Barton H, Sweeney HL, Kamm KE, Stull JT Proc. Natl. Acad. Sci. U.S.A. 2016 Jun
- Constitutive Phosphorylation of Cardiac Myosin Regulatory Light Chain in vivo.
- Chang AN, Battiprolu PK, Cowley PM, Chen G, Gerard RD, Pinto JR, Hill JA, Baker AJ, Kamm KE, Stull JT J. Biol. Chem. 2015 Mar
- In vivo roles for myosin phosphatase targeting subunit-1 phosphorylation sites T694 and T852 in bladder smooth muscle contraction.
- Chen CP, Chen X, Qiao YN, Wang P, He WQ, Zhang CH, Zhao W, Gao YQ, Chen C, Tao T, Sun J, Wang Y, Gao N, Kamm KE, Stull JT, Zhu MS J. Physiol. (Lond.) 2014 Nov
- MYPT1 Regulates the Contraction and Relaxation of Vascular Smooth Muscle and Maintains Blood Pressure.
- Qiao YN, He WQ, Chen CP, Zhang CH, Zhao W, Wang P, Zhang L, Wu YZ, Yang X, Peng YJ, Gao JM, Kamm KE, Stull JT, Zhu MS J. Biol. Chem. 2014 Jun
- Constitutive phosphorylation of myosin phosphatase targeting subunit-1 in smooth muscle.
- Tsai MH, Chang AN, Huang J, He W, Sweeney HL, Zhu M, Kamm KE, Stull JT J. Physiol. (Lond.) 2014 May
- Altered Contractile Phenotypes of Intestinal Smooth Muscle in Mice Deficient in Myosin Phosphatase Target Subunit 1.
- He WQ, Qiao YN, Peng YJ, Zha JM, Zhang CH, Chen C, Chen CP, Wang P, Yang X, Li CJ, Kamm KE, Stull JT, Zhu MS Gastroenterology 2013 Mar
- Signaling through Myosin Light Chain Kinase in Smooth Muscles.
- Gao N, Huang J, He W, Zhu M, Kamm KE, Stull JT J. Biol. Chem. 2013 Jan
- Signalling to contractile proteins by muscarinic and purinergic pathways in neurally stimulated bladder smooth muscle.
- Tsai MH, Kamm KE, Stull JT J. Physiol. (Lond.) 2012 Oct 590 Pt 20 5107-21
- Rare, nonsynonymous variant in the smooth muscle-specific isoform of myosin heavy chain, MYH11, R247C, alters force generation in the aorta and phenotype of smooth muscle cells.
- Kuang SQ, Kwartler CS, Byanova KL, Pham J, Gong L, Prakash SK, Huang J, Kamm KE, Stull JT, Sweeney HL, Milewicz DM Circ. Res. 2012 May 110 11 1411-22
- Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle.
- Stull JT, Kamm KE, Vandenboom R Arch. Biochem. Biophys. 2011 Jun 510 2 120-8
Honors & Awards
- Distinguished Basic Scientist Educator
Southwestern Medical School (2013)
- Fellow, 1990-present
American Association for the Advancement of Science (2011)
- Fouad A. and Val Imm Bashour Distinguished Chair in Physiology, 1992-present
Department of Physiology, UT Southwestern Medical Center at Dallas (2011)
- Outstanding Teacher, 2009, 2011, 2013
UT Southwestern Medical School (2009)
- University Lecture 1979, 1986, 2005
UT Southwestern Medical Center at Dallas (2005)
- Merit Award, 1991 - 2001
Heart, Lung and Blood Institute, NIH (2001)
- Associate Editor 1993-present
Journal of Biological Chemistry (1993)
- Visiting Professor
Wellcome Foundation (1990)
- Established Investigator
American Heart Association (1978)
- American Association for the Advancement of Science
- American Heart Association, Council on Basic Science
- American Physiological Society
- American Society for Biochemistry and Molecular Biology
- Biophysical Society