The ACHIEVE Program: Bringing Chicago Youth and Community Organizations Together to Impact Local Disparities.

To evaluate the Advancing Community Health and Individual leadership through a noVel Educational (ACHIEVE) program uniting Chicago high school and undergraduate students (scholars) and community organizations to empower youth to meaningfully impact communities while enhancing organizational capacity. Between 2020 and 2022, the ACHIEVE program engaged cohorts of youth in classroom-based learning and community-based projects targeting health and education disparities. Pre and post-program surveys were administered to scholars to assess knowledge about disparities, skills, and self-efficacy. Semi-structured interviews were conducted with community organization leaders to examine programmatic impact. Descriptive and thematic analyses were performed. Across four cohorts (March 2020; September 2020-May 2021; September-November 2021; March-May 2022), 85 students participated in the ACHIEVE program. Scholars supported 19 community-based projects that increased awareness of local issues and resources and evaluated programs. Scholars reported advancement in their knowledge and skills as well as interest in sustaining their community engagement. Leaders shared several benefits at the organizational and community levels from collaborating with scholars. The ACHIEVE program enabled bidirectional learning between scholars and organizations. It also demonstrated that youth can contribute positively to addressing disparities while supporting local organizations and communities.

NRAS Mutant Dictates AHCYL1-Governed ER Calcium Homeostasis for Melanoma Tumor Growth.

Calcium homeostasis is critical for cell proliferation, and emerging evidence shows that cancer cells exhibit altered calcium signals to fulfill their need for proliferation. However, it remains unclear whether there are oncogene-specific calcium homeostasis regulations that can expose novel therapeutic targets. Here, from RNAi screen, we report that adenosylhomocysteinase like protein 1 (AHCYL1), a suppressor of the endoplasmic reticulum (ER) calcium channel protein inositol trisphosphate receptor (IP3R), is selectively upregulated and critical for cell proliferation and tumor growth potential of human NRAS-mutated melanoma, but not for melanoma expressing BRAF V600E. Mechanistically, AHCYL1 deficiency results in decreased ER calcium levels, activates the unfolded protein response (UPR), and triggers downstream apoptosis. In addition, we show that AHCYL1 transcription is regulated by activating transcription factor 2 (ATF2) in NRAS-mutated melanoma. Our work provides evidence for oncogene-specific calcium regulations and suggests AHCYL1 as a novel therapeutic target for RAS mutant-expressing human cancers, including melanoma. IMPLICATIONS: Our findings suggest that targeting the AHCYL1-IP3R axis presents a novel therapeutic approach for NRAS-mutated melanomas, with potential applicability to all cancers harboring RAS mutations, such as KRAS-mutated human colorectal cancers.