Journal of Cell Biology published our work on actin polymerization controlling Hedgehog signaling Scott Atwood
Primary cilia are polarized organelles that allow detection of extracellular signals such as Hedgehog (Hh). How the cytoskeleton supporting the cilium generates and maintains a structure that finely tunes cellular response remains unclear. Here we find that regulation of actin polymerization controls primary cilia and Hh signaling. Disrupting actin polymerization, or knockdown of N-WASp/Arp3, increases ciliation frequency, axoneme length, and Hh signaling. Cdc42, a potent actin regulator, recruits both atypical Protein Kinase C iota/lambda (aPKC) and Missing-in-Metastasis (MIM) to the basal body to maintain actin polymerization and restrict axoneme length. Transcriptome analysis implicates the Src pathway as a major aPKC effector. aPKC promotes whereas MIM antagonizes Src activity to maintain proper levels of primary cilia, actin polymerization, and Hh signaling. Hh pathway activation requires Smo, Gli, and Gli1-specific activation by aPKC. Surprisingly, longer axonemes can amplify Hh signaling except when aPKC is disrupted, reinforcing the importance of the Cdc42-aPKC-Gli axis in actin-dependent regulation of primary cilia signaling. Read More PDF
Tuyen has been awarded the Susan V. Bryant Graduate Fellowship Award at the Graduate Honors Convocation! Congratulations! Scott Atwood
Dr. Susan V. Bryant is a former Dean of the Ayala School of Biological Sciences, Vice Chancellor for Research, and Executive Vice Chancellor, and has led the School and campus in numerous initiatives. Now retired, she has been an extraordinary mentor and advocate for diversity in the sciences, and continues to play an important role at the School. This fellowship recognizes her overwhelming contributions and is given to doctoral students studying developmental biology with an emphasis in stem cell regeneration.
Taylor has been awarded the SURP fellowship! Congratulations! Scott Atwood
Taylor Levee was awarded the Summer Undergraduate Research Program (SURP) fellowship at UC Irvine for the 2018 summer quarter. SURP provides funding for UCI undergraduates from all disciplines who are conducting summer research projects or creative activities under the guidance of UCI faculty members. The program offers students the opportunity to become immersed in a research topic for a full-time ten-week period, or the equivalent of 400 hours.
Kevin, Ledia, Nikita, and Tanin were awarded Excellence in Research in Biological Sciences! Congratulations! Scott Atwood
The quartet of undergraduates are the first students in the Atwood lab to participate in, and be awarded, Excellence in Research in Biological Sciences. The School of Biological Sciences believes that successful participation in creative research is one of the highest academic goals undergraduates can attain. Students enrolled in Undergraduate Research, and who meet eligibility requirements, have an opportunity to present their scientific data to the academic community at the Undergraduate Research Symposium by participating in the Excellence in Research Program. Those students who successfully complete the program are rewarded with Excellence in Research in Biological Sciences and have their research papers published in this journal.
Journal of Investigative Dermatology published our commentary on genomic stability in basal cell carcinoma Scott Atwood
Sporadic and basal cell nevus syndrome basal cell carcinomas show differential response rates to Smoothened inhibitors. Chiang et al. demonstrate notable decreases in UV-induced mutagenesis, total mutation load, genomic instability, and drug-resistant mutations among basal cell nevus syndrome basal cell carcinomas using whole exome sequencing, which may explain the differences in drug response rates. Read More PDF
Nature Medicine published our work describing GLI co-transcriptional partners SRF-MKL1 as promoters of drug-resistant basal cell carcinoma Scott Atwood
Hedgehog pathway–dependent cancers can escape Smoothened (SMO) inhibition through mutations in genes encoding canonical hedgehog pathway components; however, around 50% of drug-resistant basal cell carcinomas (BCCs) lack additional variants of these genes. Here we use multidimensional genomics analysis of human and mouse drug-resistant BCCs to identify a noncanonical hedgehog activation pathway driven by the transcription factor serum response factor (SRF). Active SRF along with its coactivator megakaryoblastic leukemia 1 (MKL1) binds DNA near hedgehog target genes and forms a previously unknown protein complex with the hedgehog transcription factor glioma-associated oncogene family zinc finger-1 (GLI1), causing amplification of GLI1 transcriptional activity. We show that cytoskeletal activation through Rho and the formin family member Diaphanous (mDia) is required for SRF–MKL-driven GLI1 activation and for tumor cell viability. Remarkably, nuclear MKL1 staining served as a biomarker in tumors from mice and human subjects to predict tumor responsiveness to MKL inhibitors, highlighting the therapeutic potential of targeting this pathway. Thus, our study illuminates, for the first time, cytoskeletal-activation-driven transcription as a personalized therapeutic target for combatting drug-resistant malignancies. Read More PDF
Baina, Kevin, Nikita, Tanin, Teja, and Yvonne have been awarded the UROP fellowship! Congratulations! Scott Atwood
Six talented undergraduates were awarded the Undergraduate Research Opportunities Program (UROP) fellowship at UC Irvine for the 2017-2018 academic year. The mission of UROP is to integrate undergraduate students into the research culture of the University by providing opportunities for faculty and students to work together on research and creative projects. UROP helps support both the research mission of the University and its educational programs while promoting an undergraduate research culture at UCI. The program fosters collaboration between students, faculty, corporate entities and government agencies to prepare the undergraduate researcher for the challenges of tomorrow. By providing professional environments conducive to research advancement and career skills development, UROP provides students with unique opportunities to develop a wide variety of skills that will be useful in any future career or educational plans. By engaging students in research and creative opportunities, the program hopes to inspire in them a life-long passion for discovery and inquiry-based learning.
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