Commentary: Race and Ethnicity in Biomedical Research - Classifications, Challenges, and Future Directions.

The use of race and ethnicity in biomedical research has been a subject of debate for the past three decades. Initially the two major race categories were: White and Black, leaving other minorities uncounted or inappropriately misclassified. As the science of health disparities evolves, more sophisticated and detailed information has been added to large databases. Despite the addition of new racial classifications, including multi-racial denominations, the quality of the data is limited to the data collection process and other social misconceptions. Although race is viewed as an imposed or ascribed status, ethnicity is an achieved status, making it a more challenging variable to include in biomedical research. Ambiguity between race and ethnicity often exists, ultimately affecting the value of both variables. To better understand specific health outcomes or disparities of groups, it is necessary to collect subgroup-specific data. Cultural perceptions and practices, health experiences, and susceptibility to disease vary greatly among broad racial-ethnic groups and requires the collection of nuanced data to understand. Here, we provide an overview of the classification of race and ethnicity in the United States over time, the existing challenges in using race and ethnicity in biomedical research and future research directions.

The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-ß signaling.

Transforming growth factor-ß (TGF-ß) signaling regulates cell proliferation and differentiation, which contributes to development and disease. Upon binding TGF-ß, the type I receptor (TGFBRI) binds TGFBRII, leading to the activation of the transcription factors SMAD2 and SMAD3. Using an RNA interference screen of the human kinome and a live-cell reporter for TGFBR activity, we identified the kinase BUB1 (budding uninhibited by benzimidazoles-1) as a key mediator of TGF-ß signaling. BUB1 interacted with TGFBRI in the presence of TGF-ß and promoted the heterodimerization of TGFBRI and TGFBRII. Additionally, BUB1 interacted with TGFBRII, suggesting the formation of a ternary complex. Knocking down BUB1 prevented the recruitment of SMAD3 to the receptor complex, the phosphorylation of SMAD2 and SMAD3 and their interaction with SMAD4, SMAD-dependent transcription, and TGF-ß-mediated changes in cellular phenotype including epithelial-mesenchymal transition (EMT), migration, and invasion. Knockdown of BUB1 also impaired noncanonical TGF-ß signaling mediated by the kinases AKT and p38 MAPK (mitogen-activated protein kinase). The ability of BUB1 to promote TGF-ß signaling depended on the kinase activity of BUB1. A small-molecule inhibitor of the kinase activity of BUB1 (2OH-BNPP1) and a kinase-deficient mutant of BUB1 suppressed TGF-ß signaling and formation of the ternary complex in various normal and cancer cell lines. 2OH-BNPP1 administration to mice bearing lung carcinoma xenografts reduced the amount of phosphorylated SMAD2 in tumor tissue. These findings indicated that BUB1 functions as a kinase in the TGF-ß pathway in a role beyond its established function in cell cycle regulation and chromosome cohesion.