News

• 8 2014

  Hedgehog Signaling in Development and Disease Meeting Scott Atwood

  I'll be presenting a poster on Smoothened variants in drug-resistant basal cell carcinoma at the 2014 Hedgehog Signaling in Development and Disease Meeting. The meeting will be held on August 4-8, 2014 in Ann Arbor, Michigan. This meeting will assemble 300 scientists studying HH signaling in myriad contexts and will feature 30 invited speakers from around the world, including North America, South America, Europe and Asia. This includes speakers from across the United States, and international speakers from 10 different countries (Australia, Canada, Chile, China, Germany, Spain, Sweden, Switzerland, Singapore, and the United Kingdom). The 2014 Hedgehog meeting will promote the exchange of data and ideas that will significantly impact our understanding of embryonic development, stem cell function and adult tissue homeostasis, as well as provide insight into the design of treatments for a growing number of Hedgehog-dependent pathologies.

• 7 2014

  Cold Spring Harbor Perspectives in Medicine published our review on advanced treatments for basal cell carcinoma Scott Atwood

  Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next generation antagonists. Read More PDF

• 6 2014

  Nature Medicine published our paper on targeting SMO-resistant tumors with a drug that suppresses the epigenetic modifyer BRD4 Scott Atwood

  Hedgehog signaling drives oncogenesis in several cancers and strategies targeting this pathway have been developed, most notably through inhibition of Smoothened. However, resistance to Smoothened inhibitors occurs via genetic changes of Smoothened or other downstream Hedgehog components. Here, we overcome these resistance mechanisms by modulating GLI transcription via inhibition of BET bromodomain proteins. We show the BET bromodomain protein, BRD4, regulates GLI transcription downstream of SMO and SUFU and chromatin immunoprecipitation studies reveal BRD4 directly occupies GLI1 and GLI2 promoters, with a substantial decrease in engagement of these sites upon treatment with JQ1, a small molecule inhibitor targeting BRD4. Globally, genes associated with medulloblastoma-specific GLI1 binding sites are downregulated in response to JQ1 treatment, supporting direct regulation of GLI activity by BRD4. Notably, patient- and GEMM-derived Hedgehog-driven tumors (basal cell carcinoma, medulloblastoma and atypical teratoid/rhabdoid tumor) respond to JQ1 even when harboring genetic lesions rendering them resistant to Smoothened antagonists. Read More PDF

• 5 2014

  Society for Investigative Dermatology Annual Meeting Scott Atwood

  I will be presenting a poster and my co-author, Dr. Kavita Sarin, will be giving a plenary talk on Smoothened variants in drug-resistant basal cell carcinomas at the 2014 Society for Investigative Dermatology (SID) annual meeting in Albuquerque, New Mexico. 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. Read More

• 3 2014

  Ataxia Investigators Meeting Scott Atwood

  I will be giving a Junior Lecturer Trainee talk on how MIM is a novel cerebellar ataxia gene in March at the Ataxia Investigators Meeting (AIM) in Las Vegas, Nevada. Hosted by the National Ataxia Foundation, these meetings bring together world-leading ataxia clinicians and scientists to accelerate ataxia research by advancing the understanding of ataxia disease mechanisms and in facilitating the push towards therapies. The National Ataxia Foundation is dedicated to improving the lives of persons affected by ataxia through support, education, and research. Read More

• 2 2014

  Another role for aPKC in Hh-dependent lung squamous cell carcinoma Scott Atwood

  Growing evidence indicates targeting aPKC may be effective in treating Hedgehog-dependent cancers. Justilien and colleagues present the surprising finding that aPKC promotes Hedgehog ligand production and lung squamous cell carcinoma growth through SOX2, rather than the canonical transcription factor GLI. Read More PDF

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