Scott has been awarded an American Cancer Society Research Scholar Grant! Scott Atwood
The American Cancer Society is on a mission to free the world from cancer. They fund and conduct research, share expert information, support patients, and spread the word about prevention. All so you can live longer — and better. The American Cancer Society is a nationwide, community-based voluntary health organization dedicated to eliminating cancer as a major health problem. The Global Headquarters are located in Atlanta, Georgia, and they have regional and local offices throughout the country to ensure a presence in every community. While most people know them for their research, they do so much more. They attack cancer from every angle. They promote healthy lifestyles to help you prevent cancer. They research cancer and its causes to find more answers and better treatments. They fight for lifesaving policy changes. They provide everything from emotional support to the latest cancer information for those who have been touched by cancer. And they do it all 24 hours a day, 7 days a week.
The lab has been awarded it's first R01 grant from the National Cancer Institute at the National Institutes of Health!Scott Atwood
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency — making important discoveries that improve health and save lives. The National Institutes of Health is made up of 27 different components called Institutes and Centers. Each has its own specific research agenda, often focusing on particular diseases or body systems. All but three of these components receive their funding directly from Congress, and administrate their own budgets. NIH leadership plays an active role in shaping the agency's research planning, activities, and outlook. The National Cancer Institute (NCI) is part of the National Institutes of Health (NIH), which is one of 11 agencies that comprise the Department of Health and Human Services (HHS). NCI, established under the National Cancer Institute Act of 1937, is the Federal Government's principal agency for cancer research and training. NCI coordinates the National Cancer Program, which conducts and supports research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer, rehabilitation from cancer, and the continuing care of cancer patients and the families of cancer patients.
Journal of Investigative Dermatology published our work on primary cilia loss drives basal to squamous cell carcinoma switchingScott Atwood
Basal cell carcinomas (BCCs) rely on Hedgehog (HH) pathway growth signal amplification by the microtubule-based organelle, the primary cilium. Despite naïve tumors responsiveness to Smoothened inhibitors (Smoi), resistance in advanced tumors remains frequent. While the resistant BCCs usually maintain HH pathway activation, squamous cell carcinomas with Ras/MAPK pathway activation also arise, with the molecular basis of tumor type and pathway selection still obscure. Here we identify the primary cilium as a critical determinant controlling tumor pathway switching. Strikingly, Smoi-resistant BCCs possess an increased mutational load in ciliome genes, resulting in reduced primary cilia and HH pathway activation compared to naive or Gorlin patient BCCs. Gene set enrichment analysis of resistant BCCs with a low HH pathway signature reveals increased Ras/MAPK pathway activation. Tissue analysis confirms an inverse relationship between primary cilia presence and Ras/MAPK activation, and primary cilia removal in BCCs potentiates Ras/MAPK pathway activation. Moreover, activating Ras in HH-responsive cell lines confers resistance to both canonical (vismodegib) and non-canonical (aPKC and MRTF inhibitors) HH pathway inhibitors, while conferring sensitivity to MAPK inhibitors. Our results provide new insights into BCC treatment and identify the primary cilium as an important lineage gatekeeper, preventing HH to Ras/MAPK pathway switching. Read More PDF
Albert, Bao, Ivan, Katherine, Vama, 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 2018-2019 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.
PNAS published our work on kinase dysregulation in multiple inherited cerebellar ataxias Scott Atwood
The genetically heterogeneous Spinocerebellar ataxias (SCAs) are caused by Purkinje neuron dysfunction and degeneration, but their underlying pathological mechanisms remain elusive. The Src family of non-receptor tyrosine kinases (SFK) are essential for nervous system homeostasis and are increasingly implicated in degerative disease. Here we reveal that the SFK suppressor Missing-in-Metastasis (MTSS1) is an ataxia locus that links multiple SCAs. MTSS1 loss results in increased SFK activity, reduced Purkinje neuron arborization, and low basal firing rates, followed by cell death. Surprisingly, mouse models for SCA1, SCA2, and SCA5 show elevated SFK activity, with SCA1 and SCA2 displaying dramatically reduced MTSS1 protein levels through reduced gene expression and protein translation, respectively. Treatment of each SCA model with a clinically-approved Src inhibitor corrects Purkinje basal firing, and delays ataxia progression in MTSS1 mutants. Our results identify a common SCA therapeutic target and demonstrate a key role for MTSS1/SFK in Purkinje neuron survival and ataxia progression. Read More PDF bioRxiv
- Older posts