Justin A. MacDonald

(1) Zipper-interacting Protein Kinase (ZIPK) and the Control of Smooth Muscle Contraction

ZIPK is a Ser/Thr-protein kinase that has been linked to the regulation of a number of processes, including cellular motility, programmed cell death and smooth muscle cell contraction. Interaction of ZIPK with different scaffolding and substrate pools have important functional implications regarding its ability to regulate vascular smooth muscle contractile capacity. Primarily, we are investigating the molecular mechanisms whereby ZIPK contributes to smooth muscle contractility through the regulation of myosin phosphatase phosphorylation. Our studies address the molecular and structural elements of ZIPK and apply this foundational information to examine the contribution of the kinase to vascular smooth muscle contractility in health and disease. Additional objectives are aimed at identifying specific ZIPK inhibitors as well as identifying ZIPK substrates through complementary chemical-genetics strategies.

(2) Smoothelin-like 1 (aka SMTNL1 or CHASM) and Smooth Muscle Contraction.

We recently discovered a novel smooth muscle protein that promotes an exaggerated vascular contractile phenotype. The SMTNL1/CHASM protein is part of an adaptive contractile response of smooth muscle to various perterbations, including exercise, aging and pregnancy. Our research examines the molecular and structural elements governing the association of SMTNL1/CHASM with important muscle proteins (i.e., calmodulin and tropomyosin) as well as the physiological significance of these interactions on vascular smooth muscle biology.

(3) NLRP Inflammasomes 

NOD-like receptors containing pyrin (NLRPs) can nucleate multimeric signaling complexes, termed inflammasomes, in response to diverse stimuli to trigger pro-inflammatory responses. Research projects examine how the ATP-binding and hydrolysis properties of the NLRP proteins integrate with signaling modules and binding partners to control innate immune responses at the molecular level.

Research Areas: 

Genomics Proteomics and Bioinformatics

Cell Signalling and Structure

Research Personnel: 

• Christina Sandall, Ph.D. Graduate Student, NSERC PGS-B Scholarship
• Tina Huey-Miin Chen, Ph.D. Graduate Student, CSM Graduate Scholarship
• Megha Murali, Ph.D. Graduate Student, CSM AIMS Scholarship
• Bjoern Ziehr, M.Sc. Graduate Student
• Lucia Wang, Administrative Assistant