Browsing by Author "Gehlhausen, Jeff R."

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    Capecitabine-induced lichenoid drug eruption: a case report
    (University of California, 2017) Gehlhausen, Jeff R.; Strausburg, Matthew B.; Aouthmany, Mouhammad; Katona, Terrence M.; Turner, Matthew J.; Dermatology, School of Medicine
    Capecitabine is a 5-fluorouracil basedchemotherapeutic drug widely used in the treatmentof solid tumors, especially colorectal and breast. Someof the most common side effects of capecitabine arecutaneous in nature, including hand-foot syndrome(palmar-plantar erythrodysesthesia). Several reports inthe literature link capecitabine use with photosensitivelichenoid eruptions. Herein, we present a case ofcapecitabine-induced lichenoid eruption in an elderlyfemale with metastatic breast cancer and discuss ourfindings in relationship to previously reported cases ofthis and other capecitabine-induced skin pathologies.
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    Phenotypic and molecular characterization of a novel mouse model of neurofibromatosis type 2
    (2015-05) Gehlhausen, Jeff R.; Clapp, D. Wade; Goebl, Mark G.; Harrington, Maureen A.; Nalepa, Grzegorz J.
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    The tumor suppressor CDKN3 controls mitosis
    (Rockefeller University Press, 2013) Nalepa, Grzegorz; Barnholtz-Sloan, Jill; Enzor, Rikki; Dey, Dilip; He, Ying; Gehlhausen, Jeff R.; Lehmann, Amalia S.; Park, Su-Jung; Yang, Yanzhu; Yang, Xianlin; Chen, Shi; Guan, Xiaowei; Chen, Yanwen; Renbarger, Jamie; Yang, Feng-Chun; Parada, Luis F.; Clapp, Wade; Pediatrics, School of Medicine
    Mitosis is controlled by a network of kinases and phosphatases. We screened a library of small interfering RNAs against a genome-wide set of phosphatases to comprehensively evaluate the role of human phosphatases in mitosis. We found four candidate spindle checkpoint phosphatases, including the tumor suppressor CDKN3. We show that CDKN3 is essential for normal mitosis and G1/S transition. We demonstrate that subcellular localization of CDKN3 changes throughout the cell cycle. We show that CDKN3 dephosphorylates threonine-161 of CDC2 during mitotic exit and we visualize CDC2(pThr-161) at kinetochores and centrosomes in early mitosis. We performed a phosphokinome-wide mass spectrometry screen to find effectors of the CDKN3-CDC2 signaling axis. We found that one of the identified downstream phosphotargets, CKβ phosphorylated at serine 209, localizes to mitotic centrosomes and controls the spindle checkpoint. Finally, we show that CDKN3 protein is down-regulated in brain tumors. Our findings indicate that CDKN3 controls mitosis through the CDC2 signaling axis. These results have implications for targeted anticancer therapeutics.