Biology subjects

Cai, W. L.

Publications and source records attributed to Cai, W. L..

3 recordsLinked to original sources

bioRxiv2024

An in vivo screen identifies NAT10 as a master regulator of brain metastasis

Metastasis is the major cause of cancer-related deaths. Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis. To better understand the epigenetic regulation of metastasis, we conducted an in vivo shRNA screen for vulnerabilities of brain metastasis and identified N-acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 significantly restrains cancer cell proliferation and migration in vitro, and tumor growth and brain metastasis in vivo. Structure-function analysis of NAT10 showed that its poorly characterized RNA helicase domain is critical for breast cancer cell growth in vitro, while its N-acetyltransferase domain is essential for primary tumor growth and brain metastasis in vivo. Integrative transcriptomic and proteomic analyses revealed key downstream effectors of NAT10, including PHGDH and PSAT1, two catalyzing enzymes for serine biosynthesis implicated in brain metastasis, and HSPA5, known to promote metastasis. We found that distant metastases of breast cancer, especially brain metastases express higher levels of NAT10, PHGDH, PSAT1, and HSPA5. Silencing PHGDH/PSAT1 or HSPA5 in metastatic breast cancer cells inhibits their ability to grow in the serine/glycine-limited condition or migrate, respectively, phenocopying the effects of NAT10 depletion. Moreover, NAT10 promotes the expression of PHGDH, PSAT1, and HSPA5 in its RNA helicase-dependent manner. These findings establish NAT10 as a master regulator of brain metastasis and shed light on the biological functions of its RNA helicase domain, nominating NAT10 as a target for treating metastatic diseases.

cancer biology↗

bioRxiv2022

Kinase-independent activity of DYRK1A promotes viral entry of highly pathogenic human coronaviruses

Identifying host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of coronavirus disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify pro-viral host factors for highly pathogenic human coronaviruses. Very few host factors were required by diverse coronaviruses across multiple cell types, but DYRK1A was one such exception. Although its role in coronavirus infection was completely unknown, DYRK1A encodes Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A and regulates cell proliferation, and neuronal development, among other cellular processes. Interestingly, individuals with Down syndrome overexpress DYRK1A 1.5-fold and exhibit 5-10x higher hospitalization and mortality rates from COVID-19 infection. Here, we demonstrate that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and MERS-CoV entry. We show that DYRK1A promotes DNA accessibility at the ACE2 promoter and a putative distal enhancer, facilitating transcription and gene expression. Finally, we validate that the pro-viral activity of DYRK1A is conserved across species using cells of monkey and human origin and an in vivo mouse model. In summary, we report that DYRK1A is a novel regulator of ACE2 and DPP4 expression that may dictate susceptibility to multiple highly pathogenic human coronaviruses. Whether DYRK1A overexpression contributes to heightened COVID-19 severity in individuals with Down syndrome through ACE2 regulation warrants further future investigation.

microbiology↗

bioRxiv2021

Peer teaching as bioinformatics training strategy: incentives, challenges, and benefits.

As biomedical research becomes more data-intensive, bioinformatics is becoming essential to understanding biological processes, systems, and diseases. In this paper we describe the use of a series of peer teaching workshops as a strategy to respond to the bioinformatics training needs at a research-intensive institution. In addition to the data collected from the workshops, we also used personal experiences of researchers who participated as peer teachers to understand the incentives, challenges, and benefits of peer teaching. Developing communication skills such as confidence in teaching, explaining complex concepts, and better understanding of the topic emerged as primary benefits that the teachers obtained from this experience. Lack of time for teaching and the struggles of classroom management were identified as two major challenges. We suggest that peer teaching can be beneficial not only to train researchers in bioinformatics, but also as a professional development opportunity for graduate students and postdoctoral trainees.

scientific communication and education↗