Tamar Tennenbaum

Novel Insights into Wound Healing Sequence of Events

Effective wound healing leads to restoration of tissue integrity and occurs through a highly organized multistage process involving various cell types. Currently, methods for wound healing assessment lack a structured system for analysis of quantitative parameters. We have established a unique quantitative assessment strategy of wound healing stages based on histological criteria. Distinctive immunohistochemical parameters including re-epithelialization, epidermal differentiation, cell migration, proliferation, inflammatory response as well as dermal closure, matrix distribution, and skin remodelling were identified and followed during the timeline of wound healing progression. Assessment was based on various defined characteristics and each stage-specific parameter was independently quantified for complete wound closure. This analysis allowed a follow-up of wound healing dynamics and identified the contribution of critical and specific parameters to wound healing physiology and pathology. In this review we demonstrate our assessment strategy of crucial wound healing events and introduce a unique quantification system for each of the processes involved in wound repair. We believe that our unique method can be utilized as a diagnostic platform for standardizing assessment of wound healing progression as well as a screening tool for potential therapies.

The Protein Kinase C Family: Key Regulators Bridging Signaling Pathways in Skin and Tumor Epithelia

Protein kinase C stands for a family of phospholipid binding/dependent serine/threonine kinases consisting of ten members subdivided into three subgroups, classical PKCs (α, βI, βII, γ), novel PKCs (δ, e, η, θ), and atypical PKCs (ζ, ι/λ), according to specific cofactor requirements. Tissue distribution and cellular compartmentalization imply differential, isoform-specific functions linked to distinct signaling cascades. Thus, certain stimuli can lead to differential responses depending on PKC isoform expression, localization, and phosphorylation status in particular biological settings. Activated by diverse extracellular signals PKCs modify the activities of cellular proteins including receptors, enzymes, cytoskeletal proteins, and transcription factors, playing a central role in signaling networks. Several isoforms participate in the regulation of proliferation, survival and cell death, but also tissue polarity and differentiation. Consequently abnormalities in PKC expression and function have been identified in several cancers. Specifically, initiation of squamous cell carcinomas and their malignant progression is associated with distinct changes in specific PKCs. Besides novel specific inhibitors (also targeting mRNAs), the generation of transgenic and knockout mice has allowed direct functional analyses of individual PKCs. Herein we focus on the role of PKCs largely in skin physiology and malignancy. Based on findings in patients, cell culture and animal models, parallels and discrepancies to other tissues are discussed.