DIANE JAWORSKI
Associate Professor
Anatomy and Neurobiology
Ph.D., Texas Womans University, 1991
Postdoctoral training, Yale University
The extracellular matrix (ECM) was once thought to simply be the relatively static material that filled the space between cells. In reality, the ECM activates signaling cascades that regulate neuronal differentiation (e.g., cell cycle arrest, neuronal migration, neurite outgrowth, and synapse elimination) and mature function (e.g., synaptic plasticity underlying learning and memory). The metzincin family of proteases, which includes matrix metalloproteinase (MMP), ADAM, and ADAM-TS members, are the main physiological mediators of ECM degradation. Metzincin proteases are dysregulated in a wide variety to neuropathologies, including Alzheimer’s and Parkinson’s disease, multiple sclerosis, and amyotrophic lateral sclerosis to name a few. To maintain tissue integrity during remodeling, metzincins are inhibited by Tissue Inhibitor of Metalloproteinases (TIMPs). Of the four TIMPs, TIMP-2 is unique in that, in addition to MMP inhibition, it is required for the conversion of latent proMMP-2 to its proteolytically active form. Furthermore, TIMP-2 functions independent of proteolysis via activation of the principal ECM receptors, integrins.
My research focuses on the role of TIMP-2 in nervous system development and disease. Three projects are currently on-going: cerebral cortical development and learning, neuromuscular maturation and myopathy, and TIMP-2 gene regulation by alternative splicing and promoter usage. Past projects investigated the role of ECM molecules (e.g., MMPs, TIMPs, and proteoglycans) in glioma invasion, stroke and experimental allergic encephalomyelitis (EAE), the mouse model of multiple sclerosis.
Lluri G, GD Langlois, B MCClellan, PD Soloway and DM Jaworski. (2006). Tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates neuromuscular junction development via a β1 integrin-mediated mechanism. Journal of Neurobiology 66:1365-77. 
Jaworski DM, P Soloway, J Caterina and WA Falls. (2006). Tissue Inhibitor of Metalloproteinase-2 (TIMP-2)-deficient mice display behavioral motor deficits. Journal of Neurobiology 66:82-94.
Perez-Martinez L and DM Jaworski. (2005). Tissue inhibitor of metalloproteinase-2 promotes neuronal differentiation by acting as an anti-mitogenic signal. Journal of Neuroscience 25:4917-29.
Jaworski DM. (2000) Differential regulation of tissue inhibitor of metalloproteinase mRNA expression in response to intracranial injury. Glia 30:199-208.
Zhang H, G Kelly, C Zerillo, DM Jaworski and S Hockfield. (1998) Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion in vivo. Journal of Neuroscience 18:2370-2376
View a complete list of Dr. Jaworski's articles via PubMed.
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