Browsing by Author "Lipchick, Brittany C"

Now showing 1 - 5 of 5

Open Access
Inhibition of the aryl hydrocarbon receptor/polyamine biosynthesis axis suppresses multiple myeloma
(Journal of Clinical Investigation, 2018-09-10) Bianchi-Smiraglia, Anna; Bagati, Archis; Fink, Emily E; Affronti, Hayley C; Lipchick, Brittany C; Moparthy, Sudha; Long, Mark D; Rosario, Spencer R; Lightman, Shivana M; Moparthy, Kalyana; Wolff, David W; Yun, Dong Hyun; Han, Zhannan; Polechetti, Anthony; Roll, Matthew V; Gitlin, Ilya I; Leonova, Katerina I; Rowsam, Aryn M; Kandel, Eugene S; Gudkov, Andrei V; Bergsagel, P Leif; Lee, Kelvin P; Smiraglia, Dominic J; Nikiforov, Mikhail A
Open Access
Internally ratiometric fluorescent sensors for evaluation of intracellular GTP levels and distribution
(Nature Methods, 2017-10) Bianchi-Smiraglia, Anna; Rana, Mitra S; Foley, Colleen E; Paul, Leslie M; Lipchick, Brittany C; Moparthy, Sudha; Moparthy, Kalyana; Fink, Emily E; Bagati, Archis; Hurley, Edward; Affronti, Hayley C; Bakin, Andrei V; Kandel, Eugene S; Smiraglia, Dominic J; Feltri, Maria Laura; Sousa, Rui; Nikiforov, Mikhail A
Open Access
Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1
(Cell Reports, 2017-09) Bagati, Archis; Bianchi-Smiraglia, Anna; Moparthy, Sudha; Kolesnikova, Kateryna; Fink, Emily E; Lipchick, Brittany C; Kolesnikova, Masha; Jowdy, Peter; Polechetti, Anthony; Mahpour, Amin; Ross, Jason; Wawrzyniak, Joseph A; Yun, Dong Hyun; Paragh, Gyorgy; Kozlova, Nadezhda I; Berman, Albert E; Wang, Jianmin; Liu, Song; Nemeth, Michael J; Nikiforov, Mikhail A
Open Access
The fatty acid elongase ELOVL6 regulates bortezomib resistance in multiple myeloma
(Blood Advances, 2021-04-13) Lipchick, Brittany C; Utley, Adam; Han, Zhannan; Moparthy, Sudha; Yun, Dong Hyun; Bianchi-Smiraglia, Anna; Wolff, David W; Fink, Emily; Liu, Liang; Furdui, Cristina M; Lee, Jingyun; Lee, Kelvin P; Nikiforov, Mikhail A
Abstract Resistance to the proteasome inhibitor bortezomib (BTZ) represents a major obstacle in the treatment of multiple myeloma (MM). The contribution of lipid metabolism in the resistance of MM cells to BTZ is mostly unknown. Here we report that levels of fatty acid elongase 6 (ELOVL6) were lower in MM cells from BTZ-nonresponsive vs BTZ-responsive patients and in cultured MM cells selected for BTZ resistance compared with parental counterparts. Accordingly, depletion of ELOVL6 in parental MM cells suppressed BTZ-induced endoplasmic reticulum (ER) stress and cytotoxicity, whereas restoration of ELOVL6 levels in BTZ-resistant MM cells sensitized them to BTZ in tissue culture settings and, as xenografts, in a plasmacytoma mouse model. Furthermore, for the first time, we identified changes in the BTZ-induced lipidome between parental and BTZ-resistant MM cell lines underlying a functional difference in their response to BTZ. We demonstrated that restoration of ELOVL6 levels in BTZ-resistant MM cells resensitized them to BTZ largely via upregulation of ELOVL6-dependent ceramide species, which was a prerequisite for BTZ-induced ER stress and cell death in these cells. Our data characterize ELOVL6 as a major clinically relevant regulator of MM cell resistance to BTZ, which can emerge from the impaired ability of these cells to alter ceramide composition in response to BTZ.
Open Access
XBP1-KLF9 Axis Acts as a Molecular Rheostat to Control the Transition from Adaptive to Cytotoxic Unfolded Protein Response
(Cell Reports, 2018-10) Fink, Emily E; Moparthy, Sudha; Bagati, Archis; Bianchi-Smiraglia, Anna; Lipchick, Brittany C; Wolff, David W; Roll, Matthew V; Wang, Jianmin; Liu, Song; Bakin, Andrei V; Kandel, Eugene S; Lee, Ann-Hwee; Nikiforov, Mikhail A