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Browsing by Subject "Drug screening"
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Item Drug screening with zebrafish visual behavior identifies carvedilol as a potential treatment for an autosomal dominant form of retinitis pigmentosa(Springer Nature, 2021-06-01) Ganzen, Logan; Ko, Mee Jung; Zhang, Mengrui; Xie, Rui; Chen, Yongkai; Zhang, Liyun; James, Rebecca; Mumm, Jeff; van Rijn, Richard M.; Zhong, Wenxuan; Pang, Chi Pui; Zhang, Mingzhi; Tsujikawa, Motokazu; Leung, Yuk Fai; Biochemistry and Molecular Biology, School of MedicineRetinitis Pigmentosa (RP) is a mostly incurable inherited retinal degeneration affecting approximately 1 in 4000 individuals globally. The goal of this work was to identify drugs that can help patients suffering from the disease. To accomplish this, we screened drugs on a zebrafish autosomal dominant RP model. This model expresses a truncated human rhodopsin transgene (Q344X) causing significant rod degeneration by 7 days post-fertilization (dpf). Consequently, the larvae displayed a deficit in visual motor response (VMR) under scotopic condition. The diminished VMR was leveraged to screen an ENZO SCREEN-WELL REDOX library since oxidative stress is postulated to play a role in RP progression. Our screening identified a beta-blocker, carvedilol, that ameliorated the deficient VMR of the RP larvae and increased their rod number. Carvedilol may directly on rods as it affected the adrenergic pathway in the photoreceptor-like human Y79 cell line. Since carvedilol is an FDA-approved drug, our findings suggest that carvedilol can potentially be repurposed to treat autosomal dominant RP patients.Item Microfluidics guided by deep learning for cancer immunotherapy screening(National Academy of Science, 2022) Ao, Zheng; Cai, Hongwei; Wu, Zhuhao; Hu, Liya; Nunez, Asael; Zhou, Zhuolong; Liu, Hongcheng; Bondesson, Maria; Lu, Xiongbin; Lu, Xin; Dao, Ming; Guo, Feng; Medical and Molecular Genetics, School of MedicineImmune-cell infiltration and cytotoxicity to pathogens and diseased cells are ubiquitous in health and disease. To better understand immune-cell behavior in a 3D environment, we developed an automated high-throughput microfluidic platform that enables real-time imaging of immune-cell infiltration dynamics and killing of the target cancer cells. We trained a deep learning algorithm using clinical data and integrated the algorithm with our microfluidic platform to effectively identify epigenetic drugs that promote T cell tumor infiltration and enhance cancer immunotherapy efficacy both in vitro and in vivo. Our platform provides a unique method to investigate immune-tissue interactions, which can be widely applied to oncology, immunology, neurology, microbiology, tissue engineering, regenerative medicine, translational medicine, and so on.Item Utilizing Zebrafish Visual Behaviors in Drug Screening for Retinal Degeneration(MDPI, 2017-06-02) Ganzen, Logan; Venkatraman, Prahatha; Pang, Chi Pui; Leung, Yuk Fai; Zhang, Mingzhi; Biochemistry and Molecular Biology, School of MedicineZebrafish are a popular vertebrate model in drug discovery. They produce a large number of small and rapidly-developing embryos. These embryos display rich visual-behaviors that can be used to screen drugs for treating retinal degeneration (RD). RD comprises blinding diseases such as Retinitis Pigmentosa, which affects 1 in 4000 people. This disease has no definitive cure, emphasizing an urgency to identify new drugs. In this review, we will discuss advantages, challenges, and research developments in using zebrafish behaviors to screen drugs in vivo. We will specifically discuss a visual-motor response that can potentially expedite discovery of new RD drugs.