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- A TH1 immune response efficiently clears rabies virus from the CNS in the absence of inflammation (1)
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Articles 1 - 7 of 7
Full-Text Articles in Medical Molecular Biology
Stabilized Core Gene And Pathway Election Uncovers Pan-Cancer Shared Pathways And A Cancer-Specific Driver, Pathum Kossinna, Weijia Cai, Xuewen Lu, Carrie S Shemanko, Qingrun Zhang
Stabilized Core Gene And Pathway Election Uncovers Pan-Cancer Shared Pathways And A Cancer-Specific Driver, Pathum Kossinna, Weijia Cai, Xuewen Lu, Carrie S Shemanko, Qingrun Zhang
Department of Cancer Biology Faculty Papers
Approaches systematically characterizing interactions via transcriptomic data usually follow two systems: (i) coexpression network analyses focusing on correlations between genes and (ii) linear regressions (usually regularized) to select multiple genes jointly. Both suffer from the problem of stability: A slight change of parameterization or dataset could lead to marked alterations of outcomes. Here, we propose Stabilized COre gene and Pathway Election (SCOPE), a tool integrating bootstrapped least absolute shrinkage and selection operator and coexpression analysis, leading to robust outcomes insensitive to variations in data. By applying SCOPE to six cancer expression datasets (BRCA, COAD, KIRC, LUAD, PRAD, and THCA) in …
Hitting The Bullseye: Are Extracellular Vesicles On Target?, Nicole Noren Hooten, María Yáñez-Mó, Rachel M. Derita, Ashley Russell, Peter Quesenberry, Bharat Ramratnam, Paul D Robbins, Dolores Di Vizio, Sicheng Wen, Kenneth W Witwer, Lucia R Languino
Hitting The Bullseye: Are Extracellular Vesicles On Target?, Nicole Noren Hooten, María Yáñez-Mó, Rachel M. Derita, Ashley Russell, Peter Quesenberry, Bharat Ramratnam, Paul D Robbins, Dolores Di Vizio, Sicheng Wen, Kenneth W Witwer, Lucia R Languino
Department of Cancer Biology Faculty Papers
No abstract provided.
Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl
Slc36a1-Mtorc1 Signaling Drives Acquired Resistance To Cdk4/6 Inhibitors., Akihiro Yoshida, Yiwen Bu, Shuo Qie, John Wrangle, E. Ramsay Camp, E. Starr Hazard, Gary Hardiman, Renée De Leeuw, Karen E. Knudsen, J. Alan Diehl
Department of Cancer Biology Faculty Papers
The cyclin-dependent kinase 4/6 (CDK4/6) kinase is dysregulated in melanoma, highlighting it as a potential therapeutic target. CDK4/6 inhibitors are being evaluated in trials for melanoma and additional cancers. While beneficial, resistance to therapy is a concern, and the molecular mechanisms of such resistance remain undefined. We demonstrate that reactivation of mammalian target of rapamycin 1 (mTORC1) signaling through increased expression of the amino acid transporter, solute carrier family 36 member 1 (SLC36A1), drives resistance to CDK4/6 inhibitors. Increased expression of SLC36A1 reflects two distinct mechanisms: (i) Rb loss, which drives SLC36A1 via reduced suppression of E2f; (ii) fragile X …
Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino
Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino
Department of Cancer Biology Faculty Papers
The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation …
Parp-1 Regulates Dna Repair Factor Availability., M J Schiewer, Amy C. Mandigo, Nicolas Gordon, Fangjin Huang, Sanchaika Gaur, Renée De Leeuw, Shuang G Zhao, Joseph Evans, Sumin Han, Theodore Parsons, Ruth Birbe, Peter Mccue, Christopher Mcnair, Saswati N. Chand, Ylenia Cendon-Florez, Peter Gallagher, Jennifer J Mccann, Neermala Poudel Neupane, Ayesha A Shafi, Emanuela Dylgjeri, Lucas J Brand, Tapio Visakorpi, Ganesh V Raj, Costas D. Lallas, Edouard J Trabulsi, Leonard G Gomella, Adam Dicker Md, Phd, William Kevin Kelly, Benjamin E Leiby, Beatrice Knudsen, Felix Y Feng, Karen E Knudsen
Parp-1 Regulates Dna Repair Factor Availability., M J Schiewer, Amy C. Mandigo, Nicolas Gordon, Fangjin Huang, Sanchaika Gaur, Renée De Leeuw, Shuang G Zhao, Joseph Evans, Sumin Han, Theodore Parsons, Ruth Birbe, Peter Mccue, Christopher Mcnair, Saswati N. Chand, Ylenia Cendon-Florez, Peter Gallagher, Jennifer J Mccann, Neermala Poudel Neupane, Ayesha A Shafi, Emanuela Dylgjeri, Lucas J Brand, Tapio Visakorpi, Ganesh V Raj, Costas D. Lallas, Edouard J Trabulsi, Leonard G Gomella, Adam Dicker Md, Phd, William Kevin Kelly, Benjamin E Leiby, Beatrice Knudsen, Felix Y Feng, Karen E Knudsen
Department of Cancer Biology Faculty Papers
PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted …
A Th1 Immune Response Efficiently Clears Rabies Virus From The Cns In The Absence Of Inflammation, Aurore Lebrun, Rhonda Kean, Jianwei Li, Douglas Craig Hooper
A Th1 Immune Response Efficiently Clears Rabies Virus From The Cns In The Absence Of Inflammation, Aurore Lebrun, Rhonda Kean, Jianwei Li, Douglas Craig Hooper
Department of Cancer Biology Faculty Papers
Little is known about CD4+ T cell entry into the central nervous system (CNS) in the absence of inflammation. Attenuated rabies viruses (RABV) are unique tools to study this process, as they spread from the site of inoculation to the CNS trans-axonally, without compromising the blood-brain barrier. Previous studies with live-attenuated RABV showed that CD4+ T cell entry into the CNS is associated with an increase in IFN-g mRNA in the brain and the production of IgG2a antibodies in the periphery, indicating a bias towards TH1 immunity. To further investigate the nature of the CD4+ T cells involved in the …
Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang
Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang
Department of Cancer Biology Faculty Papers
Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein …