Real-world findings.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to Jennifer Doyle.
Explore the source record for details and available documents.
Microvascular endothelial cells embedded within three-dimensional (3D) type I collagen matrixes assemble into cellular networks, a process that requires the upregulation of membrane type 1 (MT1) matrix metalloproteinase (MMP) and MMP-2. The purpose of this study was to identify the signaling pathways responsible for the transcriptional activation of MT1-MMP and MMP-2 in endothelial cells in 3D collagen lattices. We hypothesized that the 3D type I collagen induction of MT1-MMP and MMP-2 is mediated by the mitogen-activated protein kinase family of enzymes. Here, we show that 3D type I collagen elicits a persistent increase in ERK1/2 and JNK activation and a decrease in p38 activation. Inhibition of ERK1/2 or JNK disrupted endothelial network formation in 3D type I collagen lattices, whereas inhibition of p38 promoted network formation. mRNA levels of both MT1-MMP and MMP-2 were attenuated by ERK1/2 inhibition but unaffected by either JNK or p38 inhibition. By contrast, expression of constitutively active MEK was sufficient to stimulate MMP-2 production in a monolayer of endothelial cells cultured on type I collagen. These results provide evidence that signaling through both ERK1/2 and JNK regulates endothelial assembly into cellular networks but that the ERK1/2 signaling cascade specifically regulates network formation and the production of both MT1-MMP and MMP-2 genes in response to 3D type I collagen.
PURPOSE: Medical education reform has been the clarion call of U.S. medical educators and policymakers for two decades. To foster change and seed reform, Harvard Medical School created a professional development program for physicians and scientists actively engaged in educating future physicians that sought to transform both participants and their schools. This study focused on identifying the long-term effects of a professional development program on physician educators. METHOD: A follow-up survey of the 1995-97 cohorts of the Harvard Macy Program for Physician Educators was conducted by sending the 99 program participants a questionnaire two years after their participation. Main outcome measures studied were individual changes as reflected in participants' self-reported shifts in teaching behaviors, academic productivity, career advancement, and sense of commitment. RESULTS: A total of 63 participants completed the questionnaire, for a response rate of 63.6%. Two years following participation in the program, a majority (88.8%) of respondents reported that participation had significantly affected their professional development, including long-term changes in teaching behaviors (77.8%), engagement in new educational activities from committee work (86%) to grant funding (52.4%), and renewed vitality/identification of themselves as educators. CONCLUSIONS: Long-term follow-up of participants enrolled in an intensive program for physician educators suggests that professional development programs that create an immersion experience designed in a high-challenge, high-support environment, emphasizing experiential and participatory activities can change behaviors in significant ways, and that these changes endure over time.