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This is the introduction to the Yearbook on Critical Social Justice Across the Spectrum of Teaching and Learning: Theory and Practice in Communities and Classrooms.

Background American students represent diverse life experiences, languages, cultures, and community memberships. Given the relatively unchanged demographics of U.S. teachers (primarily middle-class, white females), it is important that teachers engage in culturally proactive pedagogy and design curriculum that both reflects their students’ culture and engages them in developing skills to be participants in a larger society. Purpose This chapter explores how three veteran eighth-grade English language arts teachers in a large middle school in the southeastern United States navigated Youth Participatory Action Research (YPAR) as a culturally proactive and socially just pedagogy and encouraged students to examine power, privilege, and oppression in literature, in informational texts, and in their local communities to identify ways they might change inequities. Research Design Findings from this qualitative study suggest that even veteran teachers often struggle to implement social justice and culturally proactive pedagogies. Findings These teachers wobbled with their own uncertainty about the differences between a more traditional pedagogy, where they drive the learning, and a critical pedagogy that places the students in charge of the direction of their learning. Conclusion/Recommendations From the findings, recommendations are made to teachers who grapple with incorporating socially just and culturally proactive pedagogies into their teaching.

Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1–3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. Cancer Res; 77(24); 6999–7013. ©2017 AACR.

In this chapter, the authors discuss the outcomes of a program evaluation of a university-middle school service-learning partnership. The initial goal was to evaluate the extent to which three middle school teachers, our community partners, were satisfied with the volunteer experience their seventh grade students had with first-year university students. The evaluation came after a three-year partnership between undergraduates enrolled in a liberal studies course focused on citizenship and education and a team of middle school students and their teachers. Interviews revealed that this partnership enabled teachers to view their students through a different lens than they had prior to the partnership. Further, teachers suggested that the service-learning activities facilitated a deeper understanding of students' funds-of-knowledge and talents. This research supports the possibility that there are valuable unintended outcomes of service-learning partnerships between universities and public schools.

Hepatocellular carcinoma (HCC) has limited treatment options and generally poor prognosis. Recent genomic studies have identified FGF19 as a driver oncogene in HCC. FGF19 is a gut secreted hormone that acts in the liver through FGFR4 to regulate bile acid synthesis. Consistent with the notion that FGF19 is a driver oncogene in HCC, transgenic mice overexpressing FGF19 form liver tumors and genetic ablation of FGFR4 prevented tumor formation. These data suggest targeting FGFR4 would have therapeutic benefit in HCC with altered FGF19 signaling. While a number of Pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by their FGFR1-3 related dose limiting toxicities. Using structure guided drug design, we have generated a highly selective covalent FGFR4 inhibitor, H3B-6527. Biochemical and cellular selectivity assays showed that H3B-6527 is >300 fold selective towards FGFR4 compared to other FGFR isoforms. Addition of H3B-6527 to FGF19 amplified HCC cell lines led to dose dependent inhibition of FGF19/FGFR4 signaling and concomitant reduction in cell viability. In a panel of 40 HCC cell lines, H3B-6527 selectively reduced the viability of cells that harbor FGF19 amplification and showed no effect in FGF19 non-amplified HCC cell line models. Oral dosing of H3B-6527 to mice led to dose-dependent pharmacodynamic modulation of FGFR4 signaling and tumor regression in FGF19 altered HCC cell line derived xenograft models. H3B-6527 demonstrated inhibition of tumor growth in an orthotopic liver xenograft model of FGF19 altered HCC grown in nude mice. Importantly, the inhibition of tumor growth occurred at doses that were well tolerated in mice and no evidence of FGFR1-3 related toxicities were observed at efficacious doses. In a panel of 30 HCC patient-derived xenograft (PDX) models, H3B-6527 demonstrated tumor regressions in the context of FGF19-amplified tumors. In addition, H3B-6527 showed antitumor activity and tumor regressions in PDX models with high FGF19 expression but no FGF19 amplification. The mechanism for FGF19 overexpression in the absence of gene amplification is under investigation. In conclusion, our preclinical studies demonstrate that FGF19 expression is a predictive biomarker for response to FGFR4 inhibitor therapy. Genomic analysis of public and proprietary data sets indicates that at least approximately 30% of HCC patients exhibit altered FGF19 expression and could potentially benefit from H3B-6527 monotherapy treatment. Citation Format: Anand Selvaraj, Erik Corcoran, Heather Coffey, Sudeep Prajapati, Ming-Hong Hao, Nicholas Larsen, Jennifer Tsai, Takashi Satoh, Kana Ichikawa, Julie Jaya Joshi, Raelene Hurley, Jeremy Wu, Chia-Ling Huang, Suzanna Bailey, Craig Karr, Pavan Kumar, Victoria Rimkunas, Crystal Mackenzie, Nathalie Rioux, Amy Kim, Sandeep Akare, George Lai, Lihua Yu, Peter Fekkes, John Wang, Markus Warmuth, Peter Smith, Dominic Reynolds. H3B6527, a selective and potent FGFR4 inhibitor for FGF19-driven hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3126. doi:10.1158/1538-7445.AM2017-3126