BACKGROUND: The ERG oncogene is activated in 50% of prostate cancers. We have designed morpholino-based oligonucleotides that target the ERG oncogene by inducing skipping of exon 4. METHODS: We designed antisense splice-switching morpholino oligonucleotides (SSOs) that target exon 4. We tested their efficacy in ERG-positive VCaP prostate cancer and MG63 osteosarcoma cell lines. We measured their effect on ERG expression, cell proliferation, migration and apoptosis in cell lines, xenografts and a radical prostatectomy sample. RESULTS: SSOs induced exon 4 skipping, reducing ERG levels up to 96 hours following transfection. SSO-induced ERG reduction decreased cell proliferation, cell migration and increased apoptosis. We observed a reduction in cyclin D1, c-Myc, β-catenin and a marker of activated Wnt signalling, p-LRP6. SSOs reduced the growth of MG63 xenografts in mice. We also demonstrated that the SSOs cause a reduction in ERG expression in a patient-derived radical prostatectomy sample ex vivo. CONCLUSIONS: We have successfully tested morpholino-based SSOs that cause a marked reduction in ERG expression, resulting in decreased cell proliferation, a reduced migratory phenotype and increased apoptosis. Our initial tests on mouse xenografts and a human prostate cancer radical prostatectomy specimen indicate that SSOs can be effective for ERG oncogene targeting in vivo.
is a professor in the Department of Electrical, Computer, and Systems Engineering (ECSE) where he teaches courses on electromagnetics, electronics and instrumentation, plasma physics, electric power, and general engineering. His research involves plasma physics, electromagnetics, photonics, biomedical sensors, engineering education, diversity in the engineering workforce, and technology enhanced learning. He learned problem solving from his father (ran a gray iron foundry), his mother (a nurse) and grandparents (dairy farmers). He has had the great good fortune to always work with amazing people, most recently professors teaching circuits and electronics from 13 HBCU ECE programs and the faculty, staff and students of the SMART LIGHTING ERC, where he is Education Director. He was ECSE
Kenneth Connor is a professor in the Department of Electrical, Computer, and Systems Engineering (ECSE) where he teaches courses on electromagnetics, electronics and instrumentation, plasma physics, electric power, and general engineering. His research involves plasma physics, electromagnetics, photonics, biomedical sensors, engineering education, diversity in the engineering workforce, and technology enhanced learning. He learned problem solving from his father (ran a gray iron foundry), his mother (a nurse) and grandparents (dairy farmers). He has had the great good fortune to always work with amazing people, most recently professors teaching circuits and electronics from 13 HBCU ECE programs and the faculty, staff and students of the SMART LIGHTING ERC, where he is Education Director. Dr. Astatke is the winner of the 2013 American Society for Engineering Education (ASEE) "National Outstanding Teaching Award," and the 2012 ASEE Mid-Atlantic Region "Distinguished Teacher" Award. He teaches courses in both analog and digital electronic circuit design and instrumentation, with a focus on wireless communication. He has more than 15 years experience in the development and delivery of synchronous and asynchronous web-based course supplements for electrical engineering courses. Dr. Astatke played a leading role in the development and implementation of the first completely online undergraduate ECE program in the State of Maryland. He has published over 50 papers and presented his research work at regional, national and international conferences. He also runs several exciting summer camps geared towards middle school, high school, and community college students to expose and increase their interest in pursuing Science Technology Engineering and Mathematics (STEM) fields. Dr. Astatke travels to Ethiopia every summer to provide training and guest lectures related to the use of the mobile laboratory technology and pedagogy to enhance the ECE curriculum at five different universities. AbstractIt is known that a large percentage of students in engineering programs switch their majors in the first two years, due to teaching methodology that is not suitable to the current population of students 9 . Integrating hands-on based learning is one of the key approaches that has been proven to be effective in improving retention by making the learning experience engaging and motivating for students. This paper addresses results of a series of pilot studies that utilized hand-held devices, specifically an Analog Discovery (AD) Board, to support experimental centric, hands-on learning in introductory engineering classes. Pilots of use of the AD Boards were shown to be successful across a variety of instructional settings. The research undergirding the findings for this paper is derived from a collaborative grant-funded project supporting a consortium of 13 public Historically Black Colleges and Universities (HBCUs) investigating the impact of using hands-on experimental-based pedagogical techniques on instruction to teach circuits con...
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