News
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12 2012
American Society for Cell Biology Annual Meeting Scott Atwood
I will be giving a talk on how aPKC activates Hedgehog signaling during basal cell carcinoma growth at the American Society
for Cell Biology Annual Meeting, located in San Francisco, from December 15-19. As the premier international meeting in the field of cell biology, the ASCB Annual Meeting is intended for scientists and students in academia,
industry, government, and higher education. Over 100 scientific sessions and 3,000 poster presentations cover a variety of scientific areas within the discipline. With opportunities to learn about the latest research and network
with peers, the ASCB Annual Meeting appeals to the diverse interests of the international cell biology community.
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10 2012
Journal of Cell Biology published our review on therapeutic advances in basal cell carcinoma treatment Scott Atwood
Dependence of basal cell carcinomas and medulloblastomas on the Hedgehog pathway provides an opportunity for targeted or personalized therapy.
The recent effectiveness and FDA approval of the first Smoothened inhibitors validates this class of agents, but has revealed drug-resistant tumor variants that bypass Smoothened inhibition. Here, we summarize the effectiveness
of Hedgehog pathway inhibitors and highlight promising areas for the development of next generation drug antagonists for Hedgehog-dependent cancers.
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7 2012
Singapore signalling: the 2012 hedgehog pathway cocktail Scott Atwood
The meeting report for the Hedgehog Signalling in Development, Evolution, and Disease conference from EMBO reports is
here and our work on aPKC-dependent regulation of Hedgehog signaling in basal cell carcinoma was highlighted in the Signalling
section! The conference took place in Biopolis, Singapore and brought Hedgehog signaling experts together to discuss their latest work and exchange ideas. A striking mix of cultures combined with gleaming skycrapers and colonial
buildings cultivated a brilliant meeting.
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4 2012
Journal of Biological Chemistry published our paper on Par-6-dependent regulation of aPKC Scott Atwood
Atypical Protein Kinase C (aPKC) controls cell polarity by modulating substrate cortical localization. Aberrant aPKC activity disrupts polarity yet
the mechanisms that control aPKC remain poorly understood. We used a reconstituted system with purified components and a cultured cell cortical displacement assay to investigate aPKC regulation. We find that aPKC is autoinhibited
by two domains within its NH2-terminal regulatory half, a pseudosubstrate motif that occupies the kinase active site, and a C1 domain that assists in this process. The Par complex member Par-6, previously thought to inhibit aPKC,
is a potent activator of aPKC in our assays. Par-6 and aPKC interact via PB1 domain heterodimerization and this interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par-6 CRIB-PDZ domains.
We propose that, along with its previously described roles in controlling aPKC localization, Par-6 allosterically activates aPKC to allow for high spatial and temporal control of substrate phosphorylation and polarization.
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3 2012
Hedgehog Signalling in Development, Evolution, and Disease Meeting Scott Atwood
I will be giving a talk on how aPKC activates Hedgehog signaling during basal cell carcinoma growth at the Hedgehog Signalling in Development, Evolution,
and Disease Conference held at Biopolis, located in Singapore, from March 18-21. The goal of the Hedgehog Conference is to bring together the leading researchers in the Hedgehog field to present their most recent findings and ideas.
First discovered in Drosophila, Hedgehog signaling research over the past 15 years has revealed the essential role played by Hedgehog in development and disease. In fact, aberrant Hedgehog signaling is associated with 25% of all
human cancers. The meeting reflects many areas of Hedgehog signaling, with sessions devoted to the mechanisms of signal transduction, developmental roles of Hedgehog, evolutionary origins of the pathway, involvement in human disease,
and use as therapeutic targets. Dr. Wei-Meng Woo, a postdoctoral research fellow in the Oro lab, will also give a talk on a Noggin-Shh regulatory loop in the dermal papilla that regulates hair morphogenesis.
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9 2011
Scientific Highlights from the 71st Annual Meeting of the Society for Investigative Dermatology Scott Atwood
The meeting report for the Society for Investigative Dermatology is finally
here and our work on aPKC regulation of basal cell carcinoma was highlighted in the Cancer section! An international group of about 1,500 researchers
attended the SID meeting to hear cutting-edge research in skin health and disease. Almost 900 oral and poster presentations were given, and our work was one of the few highlighted in the meeting report. Fellow Stanford University
postdoctoral scholars Markus Kretz and Carolyn Lee's work on long noncoding RNAs in skin differentiation and development was also highlighted. Congratulations!
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7 2011
Gordon Conference on Epithelial Differentiation and Keratinization Scott Atwood
I will be giving a talk on aPKC-dependent regulation of basal cell carcinoma at the Epithelial Differentiation and Keratinization Gordon Conference held
at Mount Snow Resort, located in West Dover, Vermont, during the first week in July. The goal of the Gordon Research Conference on Epithelial Differentiation and Keratinization is to provide a stimulating forum for the dissemination
and discussion of new research, concepts and opportunities at the forefront of epidermal and epithelial biology. Since its inception in 1979, this conference has fostered interactions among clinical and basic scientists. The epidermis
and its appendages have historically been a central focus, but the 2011 conference will include discussion of additional epithelial tissues and models. The aims of the Conference are to define the most important problems and
opportunities at the frontiers of epithelial biology; further the development of young investigators; and introduce new concepts and advances from other fields. To accomplish these goals, the program for 2011 emphasizes exciting new
research on the epidermal barrier; regulation and therapeutic applications of skin stem cells; the role of the immune system in epithelial biology and disease; signaling in epithelial homeostasis and cancer; and novel mechanisms
involving regulatory RNAs, chromatin remodeling, and adhesion.
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5 2011
Society for Investigative Dermatology Annual Meeting Scott Atwood
I will be giving a plenary talk on novel factors that regulate Hedgehog signaling in basal cell carcinoma at the 2011 Society for Investigative
Dermatology (SID) annual meeting in Phoenix. I have also been awarded the Albert M. Kligman Travel Fellowship. The SID was born out of a vision to serve a segment of science previously unrepresented by the medical societies of
the United States: investigative dermatology. The founders saw a need for an organization with a devotion to cutaneous investigation, rather than clinical work, and to promote investigative dermatology to a fully respected position
among the medical specialties. In tandem with the establishment of the society, they sought to develop a new scientific journal that would act as a singular resource for investigative work in cutaneous biology. Previously, this
research had been scattered among the non-dermatology journals and had largely been completed outside the specialty of investigative dermatology. This vision was realized when the SID was founded, bylaws were adopted and a board of
nine directors was appointed on June 10, 1937 at the Hotel Dennis in Atlantic City, New Jersey. The Journal of Investigative Dermatology (JID) was launched, with Marion B. Sulzberger as its first editor, and the first Annual
Meeting was held in April 1938 in New York City.
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8 2010
Preview of our paper in Developmental Cell Scott Atwood
Signaling circuits often coordinate cellular membranes and actin filaments at distinct sites to direct cell behavior. In this issue of Developmental Cell, Bershteyn et al. outline how the molecular scaffold protein, MIM, which bends membranes and binds actin filaments, is at the middle of one such circuit to regulate ciliogenesis. Read More
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8 2010
Developmental Cell published our paper on MIM-dependent regulation of ciliogenesisScott Atwood
The primary cilium is critical for transducing Sonic hedgehog (Shh) signaling, but the mechanisms of its transient assembly are poorly understood.
Previously we showed that the actin regulatory protein Missing-in-Metastasis (MIM) regulates Shh signaling, but the nature of MIM's role was unknown. Here we show that MIM is required at the basal body of mesenchymal cells for
cilia maintenance, Shh responsiveness, and de novo hair follicle formation. MIM knockdown results in increased Src kinase activity and subsequent hyperphosphorylation of the actin regulator Cortactin. Importantly, inhibition of
Src or depletion of Cortactin compensates for the cilia defect in MIM knockdown cells, whereas overexpression of Src or phospho-mimetic Cortactin is sufficient to inhibit ciliogenesis. Our results suggest that MIM promotes
ciliogenesis by antagonizing Src-dependent phosphorylation of Cortactin and describe a mechanism linking regulation of the actin cytoskeleton with ciliogenesis and Shh signaling during tissue regeneration.
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