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Christian, S. L.

Publications and source records attributed to Christian, S. L..

2 recordsLinked to original sources

Equity in Action: A Four-Year journey towards Gender Parity and Racial Diversity in Biochemistry Hiring

Recruitment of faculty members in academic departments shapes the department for decades in both research and teaching arenas. Having a diverse department is beneficial for undergraduate and graduate students as representation of underrepresented minority groups in the professoriate can inspire a greater diversity of students to pursue higher levels of education or research-focused careers. Increased diversity benefits research directly as diverse teams have been shown to have better ideas and outcomes. In 2020, our department had lower gender diversity than would be expected based on the pool of PhD students and post-doctoral fellows in Canada. Therefore, we altered our hiring process, primarily by redacting applications, for recruitment into entry-level tenure-track faculty positions. With this change in process, female hires increased from 17% in the previous ten years (5 hires) to 80% in the subsequent four years (5 hires) with no substantial change in hiring of racially diverse individuals (50% to 40%). Overall, combined with retirements, the percentage of female faculty in the department went from 25% to 50% and the percentage of racialized faculty went from 38% to 44%. The new hires have met or exceeded expectations of success with respect to grant funding and are on track to meet or exceed expectations for other metrics of success. Thus, our intervention was very successful in increasing the diversity of our department within a short timeframe. We believe that our experience could provide other departments with a template for making substantive change, even in the absence of internal expertise in the area. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/617211v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@164c310org.highwire.dtl.DTLVardef@42585borg.highwire.dtl.DTLVardef@1b6f6eaorg.highwire.dtl.DTLVardef@10ca067_HPS_FORMAT_FIGEXP M_FIG C_FIG

scientific communication and education↗

CD24 regulates extracellular vesicle release via an aSMase/PI3K/mTORC2/ROCK/actin pathway in B lymphocytes

CD24 is a glycophosphatidylinositol-linked protein that regulates B cell development. We previously reported that stimulation of CD24 on donor B cells promotes the transfer of functional receptors to recipient B cells via extracellular vesicles (EVs). However, the mechanisms regulating CD24-mediated formation of bioactive EVs are unknown. Using bioinformatics, we found a connection between CD24, and PI3K/AKT and mTOR. To determine if these pathways regulate EV release, we used flow cytometry to follow the transfer of EVs carrying lipid- associated GFP and surface IgM from donor to recipient B cells. Using chemical and genetic inhibition, we found that a PI3K/mTORC2/ROCK/actin pathway regulates bioactive EV formation via activation of acid sphingomyelinase (aSMase) upstream of PI3K. Using single EV analysis, we found that CD24 regulates the formation of the subset of bioactive EVs that are taken up by recipient cells and not total EVs. Interestingly, we also found that ROCK and aSMase modulate ectosome but not exosome formation, when CD24 is stimulated. Lastly, through live cell imaging, we found that PI3K and ROCK are required for inducing membrane dynamics associated with EV formation. These data suggest that this pathway regulates bioactive EV release that, in turn, could regulate B cell development. Graphical TOC/AbstractO_LIBioinformatics analysis followed by genetic and chemical experiments revealed that a novel pathway regulates EV release downstream of CD24; namely aSMase/PI3K/mTORC2/ROCK/actin. C_LIO_LISingle EV analysis suggests that the EVs are ectosomes and that CD24 regulates packaging of cargo to create bioactive vesicles rather than regulating total EV release. C_LIO_LILive cell imaging shows that CD24 regulates membrane dynamics. C_LI O_FIG O_LINKSMALLFIG WIDTH=167 HEIGHT=200 SRC="FIGDIR/small/607772v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@262ac2org.highwire.dtl.DTLVardef@1c150b0org.highwire.dtl.DTLVardef@98779dorg.highwire.dtl.DTLVardef@1d51803_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗