Browsing by Author "Qu, Pingping"

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    Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons
    (National Academy of Sciences, 2021) Pak, ChangHui; Danko, Tamas; Mirabella, Vincent R.; Wang, Jinzhao; Liu, Yingfei; Vangipuram, Madhuri; Grieder, Sarah; Zhang, Xianglong; Ward, Thomas; Huang, Yu-Wen Alvin; Jin, Kang; Dexheimer, Philip; Bardes, Eric; Mitelpunkt, Alexis; Ma, Junyi; McLachlan, Michael; Moore, Jennifer C.; Qu, Pingping; Purmann, Carolin; Dage, Jeffrey L.; Swanson, Bradley J.; Urban, Alexander E.; Aronow, Bruce J.; Pang, Zhiping P.; Levinson, Douglas F.; Wernig, Marius; Südhof, Thomas C.; Neurology, School of Medicine
    Heterozygous NRXN1 deletions predispose to schizophrenia and other neurodevelopmental disorders. Engineered heterozygous NRXN1 deletions impair neurotransmitter release in human neurons, suggesting a synaptic pathophysiological mechanism. In a multicenter effort to test the generality and robustness of this pivotal observation, we used, at two laboratories, independent analyses of patient-derived and newly engineered human neurons with heterozygous NRXN1 deletions. Schizophrenia patient-derived neurons with NRXN1 deletions exhibited the same major decrease in neurotransmitter release and an increase in CASK protein as engineered human neurons with NRXN1 deletions. Strikingly, engineered mouse Nrxn1-deficient neurons derived by the same method displayed no such phenotype, suggesting a human-specific role for NRXN1. Thus, heterozygous NRXN1 deletions robustly impair synaptic function in human neurons, enabling future drug discovery efforts.
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    PHF19 inhibition as a therapeutic target in Multiple Myeloma
    (Elsevier, 2021) Schinke, Carolina D.; Bird, Jordan T.; Qu, Pingping; Yaccoby, Shmuel; Lyzogubov, Valeriy V.; Shelton, Randal; Ling, Wen; Boyle, Eileen M.; Deshpande, Sharyu; Byrum, Stephanie D.; Washam, Charity; Mackintosh, Samuel; Stephens, Owen; Thanendrarajan, Sharmilan; Zangari, Maurizio; Shaughnessy, John, Jr.; Zhan, Fenghuang; Barlogie, Bart; van Rhee, Frits; Walker, Brian A.; Medicine, School of Medicine
    Epigenetic deregulation is increasingly recognized as a contributing pathological factor in multiple myeloma (MM). In particular tri-methylation of H3 lysine 27 (H3K27me3), which is catalyzed by PHD finger protein 19 (PHF19), a subunit of the Polycomb Repressive Complex 2 (PRC2), has recently shown to be a crucial mediator of MM tumorigenicity. Overexpression of PHF19 in MM has been associated with worse clinical outcome. Yet, while there is mounting evidence that PHF19 overexpression plays a crucial role in MM carcinogenesis downstream mechanisms remain to be elucidated. In the current study we use a functional knock down (KD) of PHF19 to investigate the biological role of PHF19 and show that PHF19KD leads to decreased tumor growth in vitro and in vivo. Expression of major cancer players such as bcl2, myc and EGR1 were decreased upon PHF19KD further underscoring the role of PHF19 in MM biology. Additionally, our results highlighted the prognostic impact of PHF19 overexpression, which was significantly associated with worse survival. Overall, our study underscores the premise that targeting the PHF19-PRC2 complex would open up avenues for novel MM therapies.