Article
Multidisciplinary Sciences
Delphine Lissa, Nobuyuki Takahashi, Parth Desai, Irena Manukyan, Christopher W. Schultz, Vinodh Rajapakse, Moises J. Velez, Deborah Mulford, Nitin Roper, Samantha Nichols, Rasa Vilimas, Linda Sciuto, Yuanbin Chen, Udayan Guha, Arun Rajan, Devon Atkinson, Rajaa El Meskini, Zoe Weaver Ohler, Anish Thomas
Summary: This study explores the clinical significance and biological characteristics of neuroendocrine subtypes in small cell lung cancer, as well as the complex variability within and between tumors. NE tumors are more likely to respond to certain treatments but show resistance to chemotherapy, while non-NE tumors may benefit more from immunotherapy.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Zhuolin Li, Yuxin He, Yanjun Li, Juan Li, Hezhao Zhao, Guanbing Song, Makoto Miyagishi, Shourong Wu, Vivi Kasim
Summary: NeuroD1 is positively correlated with G6PD in colorectal cancer cells, and its regulation alters tumor cell metabolism by stimulating the pentose phosphate pathway, leading to increased production of nucleotides and NADPH, while decreasing reactive oxygen species levels.
Article
Gastroenterology & Hepatology
Yu Song, Jiayi Wei, Rong Li, Ruifeng Fu, Pei Han, Heming Wang, Guangcong Zhang, Shuyu Li, Sinuo Chen, Zhiyong Liu, Yicheng Zhao, Changfeng Zhu, Jimin Zhu, Shuncai Zhang, Hao Pei, Jiefei Cheng, Jian Wu, Ling Dong, Guangqi Song, Xizhong Shen, Qunyan Yao
Summary: TrkB is decreased in liver fibrosis and its overexpression can inhibit the activation of TGF-beta/SMAD signaling and alleviate hepatic fibrosis, making it a potential therapeutic target.
Article
Multidisciplinary Sciences
Romana Bohuslavova, Valeria Fabriciova, Ondrej Smolik, Laura Lebron-Mora, Pavel Abaffy, Sarka Benesova, Daniel Zucha, Lukas Valihrach, Zuzana Berkova, Frantisek Saudek, Gabriela Pavlinkova
Summary: NEUROD1 is a transcription factor that plays an important role in pancreatic development and is crucial for the differentiation of endocrine cells. Its deficiency disrupts endocrine cell identity acquisition and compromises their differentiation and functional properties.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Zhiyang Jiang, Jiadong Pan, Jiahui Lu, Jie Mei, Rui Xu, Dandan Xia, Xuejing Yang, Huiyu Wang, Chaoying Liu, Junying Xu, Junli Ding
Summary: This study comprehensively explored the composition and clinical significance of tumor-infiltrating lymphocytes (TILs) in pancreatic cancer (PaCa). It revealed distinct infiltrating features of different types of TILs in PaCa and established a 6-TILs signature for prognostic prediction in PaCa patients.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Developmental Biology
Aditi Singh, Arun Mahesh, Florian Noack, Beatriz Cardoso de Toledo, Federico Calegari, Vijay K. Tiwari
Summary: Corticogenesis is a complex process involving various events, and the interaction between Tcf12 and NeuroD1 plays a crucial role in gene expression and cell migration, contributing to proper cortical development.
Article
Oncology
Xuexi Zhang, Hao Wang, Wenxu Liu, Zengtuan Xiao, Zhenyi Ma, Zhenfa Zhang, Wenchen Gong, Jun Chen, Zhe Liu
Summary: Using single-cell RNA-Seq, it was found that ASCL1(+) and NEUROD1(+) subtypes coexist within the same small cell lung cancer tissue. NEUROD1(+) cells have reduced epithelial features and lack EPCAM expression compared to ASCL1(+) cells. NEUROD1(+) cells exhibit higher metastatic capability and can be derived from ASCL1(+) cells.
BRITISH JOURNAL OF CANCER
(2023)
Letter
Neurosciences
Yanxia Rao, Bo Peng
Summary: The debate on NeuroD1-induced microglia-to-neuron conversion has recently been addressed. A study published in Neuron demonstrates that NeuroD1 is unable to induce such conversion. However, researchers who observed the conversion responded, claiming that the failure to observe it in vitro was due to low NeuroD1 expression efficiency. The authors of the original study refute this claim, stating that their NeuroD1 expression level was comparable to the other study, or even higher.
Article
Biochemistry & Molecular Biology
Zheng-Kui Weng, Te-Hsien Lin, Kuo-Hsuan Chang, Ya-Jen Chiu, Chih-Hsin Lin, Pei-Hsuan Tseng, Ying-Chieh Sun, Wenwei Lin, Guey-Jen Lee-Chen, Chiung-Mei Chen
Summary: This study found that compounds ZN-015, VB-030, and VB-037 can alleviate Tau protein neurotoxicity and promote neurite outgrowth by enhancing BDNF/TRKB signaling pathway activation.
Article
Multidisciplinary Sciences
Feng Gu, Isabel Parada, Tao Yang, Frank M. Longo, David A. Prince
Summary: Dravet syndrome is a severe childhood epilepsy caused by mutations in the Scn1a gene. Early treatment with a partial BDNF TrkB receptor agonist can improve PV interneuron function, reduce seizures, and increase survival rates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Charles Le Cicle, Vincent Pacini, Nicolas Rama, Servane Tauszig-Delamasure, Eloise Airaud, Florence Petit, Simon de Beco, Joelle Cohen-Tannoudji, David L'hote
Summary: Pituitary gonadotrope cells play a crucial role in the endocrine regulation of reproduction, but the molecular mechanisms underlying the organization of these cells during embryogenesis are poorly understood. This study identified NEUROD1 and NEUROD4 as regulators of genes involved in the focal adhesion pathway, and demonstrated that they affect cell adhesion and motility of gonadotrope cells. The study also revealed that NTRK3 is a major regulator of gonadotrope cell motility through its interaction with c-Src, and it is involved in the positioning of gonadotrope cells within the developing pituitary.
CELL DEATH DISCOVERY
(2023)
Article
Pharmacology & Pharmacy
Yuko Fujita, Yaeko Hashimoto, Hiroyo Hashimoto, Lijia Chang, Kenji Hashimoto
Summary: The study demonstrated that (R)-ketamine can alleviate inflammation symptoms and depression in DSS-induced UC mouse model by reducing colon shortening and elevated levels of interleukin-6 caused by DSS treatment. The beneficial effects were found to be dependent on TrkB stimulation, suggesting (R)-ketamine as a potential novel therapeutic drug for inflammatory bowel diseases like UC.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Jing Wang, Yichen Cai, Jingyi Sun, Hua Feng, Xiaoyu Zhu, Qian Chen, Feng Gao, Qingbin Ni, Leilei Mao, Mingfeng Yang, Baoliang Sun
Summary: In this study, non-invasive treatment methods using AAV vectors carrying BDNF or TrkB genes were performed on stroke-injured rats. The combination therapy significantly improved upper limb motor functional recovery and neurotransmission efficiency, promoting axonal remodeling and restoration of synaptic structures.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Chemistry, Medicinal
Piotr Pankiewicz, Marcin Szybinski, Katarzyna Kisielewska, Filip Golebiowski, Patryk Krzeminski, Izabela Rutkowska-Wlodarczyk, Rafal Moszczynski-Petkowski, Lidia Gurba-Bryskiewicz, Monika Delis, Krzysztof Mulewski, Damian Smuga, Jakub Dominowski, Artur Janusz, Michal Gorka, Krzysztof Abramski, Agnieszka Napiorkowska, Marcin Nowotny, Krzysztof Dubiel, Katarzyna Kalita, Maciej Wieczorek, Jerzy Pieczykolan, Mikolaj Matloka
Summary: This study aimed to validate the pharmacology of 7,8-DHF as a TrkB agonist, but results showed no observed activity against the TrkB receptor in cell lines or relevant pharmacokinetic properties for in vivo use. The lack of selectivity and distinct functional profile independent of TrkB interaction suggest caution in interpreting the reported pharmacological activity of compounds like 7,8-DHF in a broader functional context.
Article
Biochemistry & Molecular Biology
Romana Bohuslavova, Ondrej Smolik, Jessica Malfatti, Zuzana Berkova, Zaneta Novakova, Frantisek Saudek, Gabriela Pavlinkova
Summary: The research shows that NEUROD1 plays a crucial role in mouse pancreas development, and its deletion affects the expression of key transcription factors, cell proliferation, insulin production, and formation of islets of Langerhans, resulting in severe diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Ling Cai, Hongyu Liu, Fang Huang, Junya Fujimoto, Luc Girard, Jun Chen, Yongwen Li, Yu-An Zhang, Dhruba Deb, Victor Stastny, Karine Pozo, Christin S. Kuo, Gaoxiang Jia, Chendong Yang, Wei Zou, Adeeb Alomar, Kenneth Huffman, Mahboubeh Papari-Zareei, Lin Yang, Benjamin Drapkin, Esra A. Akbay, David S. Shames, Ignacio I. Wistuba, Tao Wang, Jane E. Johnson, Guanghua Xiao, Ralph J. DeBerardinis, John D. Minna, Yang Xie, Adi F. Gazdar
Summary: This study revealed the connection between immune phenotypes and NE scores, as well as the differences in immune gene expression between classic SCLC and variant SCLC. The research demonstrated the re-expression of MHC I in SCLC upon development of chemoresistance. These findings provide guidance for the design of treatment regimens in SCLC.
COMMUNICATIONS BIOLOGY
(2021)
Article
Oncology
Rafal Dziadziuszko, Tony Mok, Solange Peters, Ji-Youn Han, Jorge Alatorre-Alexander, Natasha Leighl, Virote Sriuranpong, Maurice Perol, Gilberto de Castro Junior, Ernest Nadal, Filippo de Marinis, Osvaldo Aren Frontera, Daniel S. W. Tan, Dae Ho Lee, Hye Ryun Kim, Mark Yan, Todd Riehl, Erica Schleifman, Sarah M. Paul, Simonetta Mocci, Rajesh Patel, Zoe June Assaf, David S. Shames, Michael S. Mathisen, Shirish M. Gadgeel
Summary: The study demonstrated the clinical application of blood-based next-generation sequencing technology in ALK-positive NSCLC patients, showing good efficacy and safety of alectinib treatment. The research also investigated the treatment outcomes of patients with baseline CNS metastases and the relationship between circulating biomarkers and treatment response.
JOURNAL OF THORACIC ONCOLOGY
(2021)
Article
Oncology
Shirish Gadgeel, Fred R. Hirsch, Keith Kerr, Fabrice Barlesi, Keunchil Park, Achim Rittmeyer, Wei Zou, Namrata Bhatia, Hartmut Koeppen, Sarah M. Paul, David Shames, Jing Yi, Christina Matheny, Marcus Ballinger, Mark McCleland, David R. Gandara
Summary: This study suggests that both the SP142 and 22C3 assays have similar predictive value for the efficacy of atezolizumab in patients with metastatic non-small cell lung cancer. The use of atezolizumab was associated with greater survival regardless of the assay used to determine tumor PD-L1 status.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Claire F. Friedman, John D. Hainsworth, Razelle Kurzrock, David R. Spigel, Howard A. Burris, Christopher J. Sweeney, Funda Meric-Bernstam, Yong Wang, Jonathan Levy, Jessica Grindheim, David S. Shames, Katja Schulze, Arisha Patel, Charles Swanton
Summary: Atezolizumab monotherapy showed promising clinical activity in patients with TMB >= 16 mut/Mb tumors lacking other suitable treatment options and who were immunotherapy-naive at enrollment, regardless of microsatellite instability status. Limited activity was observed in tumors with TMB >= 10 and < 16 mut/Mb.
Article
Oncology
Howard Jack West, Mark McCleland, Federico Cappuzzo, Martin Reck, Tony Sk Mok, Robert M. Jotte, Makoto Nishio, Eugene Kim, Stefanie Morris, Wei Zou, David Shames, Meghna Das Thakur, Geetha Shankar, Mark A. Socinski
Summary: Atezolizumab combined with bevacizumab and chemotherapy is an effective first-line treatment in metastatic non-squamous non-small cell lung cancer subgroups with mKRAS and co-occurring STK11 and/or KEAP1 or TP53 mutations and/or high PD-L1 expression. Mutation of STK11 and/or KEAP1 can serve as poor prognostic indicators.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Cell Biology
Ji-Ung Jung, Anwesha B. Ghosh, Svetlana Earnest, Staci L. Deaton, Melanie H. Cobb
Summary: The protein kinase WNK1 is involved in maintaining cellular ion homeostasis and its accumulation can lead to familial hypertension. This study investigates the degradation pathways of WNK1 and identifies UBR5 as a regulator of WNK1 protein stability that leads to lysosomal degradation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Oncology
Namrata S. Patil, Barzin Y. Nabet, Soeren Mueller, Hartmut Koeppen, Wei Zou, Jennifer Giltnane, Amelia Au-Yeung, Shyam Srivats, Jason H. Cheng, Chikara Takahashi, Patricia E. de Almeida, Avantika S. Chitre, Jane L. Grogan, Linda Rangell, Sangeeta Jayakar, Maureen Peterson, Allison W. Hsia, William E. O'Gorman, Marcus Ballinger, Romain Banchereau, David S. Shames
Summary: The study revealed that inhibitors of the PD-1/PD-L1 signaling axis have a significant overall survival benefit for non-small cell lung cancer (NSCLC) patients. Transcriptomic analysis and single-cell RNA sequencing showed that B and plasma cells play an important role in the efficacy of PD-L1 blockade in NSCLC.
Article
Biochemistry & Molecular Biology
Edward S. Kim, Vamsidhar Velcheti, Tarek Mekhail, Cindy Yun, Sarah M. Shagan, Sylvia Hu, Young Kwang Chaes, Ticiana A. Leal, Jonathan E. Dowell, Michaela L. Tsai, Christopher S. R. Dakhil, Philip Stella, Yanling Jin, David S. Shames, Erica Schleifman, David A. Fabrizio, See Phan, Mark A. Socinski
Summary: In patients with non-small cell lung cancer, blood TMB shows potential as a predictive biomarker for first-line atezolizumab monotherapy, with higher ORR in the high bTMB group. However, the results for PFS were not statistically significant. Additionally, at 36.5-month follow-up, bTMB >= 16 was associated with longer OS compared to bTMB < 16.
Article
Biochemistry & Molecular Biology
Jamie E. Chaft, Filiz Oezkan, Mark G. Kris, Paul A. Bunn, Ignacio I. Wistuba, David J. Kwiatkowski, Dwight H. Owen, Yan Tang, Bruce E. Johnson, Jay M. Lee, Gerard Lozanski, Maciej Pietrzak, Michal Seweryn, Woo Yul Byun, Katja Schulze, Alan Nicholas, Ann Johnson, Jessica Grindheim, Stephanie Hilz, David S. Shames, Chris Rivard, Eric Toloza, Eric B. Haura, Ciaran J. McNamee, G. Alexander Patterson, Saiama N. Waqar, Valerie W. Rusch, David P. Carbone
Summary: This study examined the use of neoadjuvant atezolizumab in patients with resectable non-small cell lung cancer. It found that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but further studies are needed to confirm these findings.
Article
Biochemistry & Molecular Biology
Solange Peters, Rafal Dziadziuszko, Alessandro Morabito, Enriqueta Felip, Shirish M. Gadgeel, Parneet Cheema, Manuel Cobo, Zoran Andric, Carlos H. Barrios, Masafumi Yamaguchi, Eric Dansin, Pongwut Danchaivijitr, Melissa Johnson, Silvia Novello, Michael S. Mathisen, Sarah M. Shagan, Erica Schleifman, Jin Wang, Mark Yan, Simonetta Mocci, David Voong, David A. Fabrizio, David S. Shames, Todd Riehl, David R. Gandara, Tony Mok
Summary: Selection of non-small cell lung cancer patients based on high blood-based tumor mutation burden did not improve clinical response, further research is needed.
Article
Biochemistry & Molecular Biology
Clinton A. Taylor, Kevin W. Cormier, Ana Martin-Vega, Svetlana Earnest, Steve Stippec, Chonlarat Wichaidit, Melanie H. Cobb
Summary: The most frequent ERK2 mutation in cancers, E322K, is located in the common docking (CD) site, affecting its binding with activators, inactivating phosphatases, and substrates. Another mutation, D321N, also affects the CD site but less frequently. These gain-of-function mutations have been found to have subtle differences in behavior, such as increased nuclear retention and disrupted dimer interface.
Article
Multidisciplinary Sciences
Ji-Ung Jung, Melanie H. Cobb
Summary: The protein kinase WNK1 influences the trafficking and actin polymerization of membrane proteins. This study discovered a connection between WNK1 and TRIM27, which regulates endosomal actin polymerization. Depletion of WNK1 disrupted WASH ubiquitination and endosomal actin polymerization, affecting endosomal trafficking. Depletion of WNK1 or TRIM27 increased the degradation of EGFR in cancer cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Wang Yuan, Yi M. Weaver, Svetlana Earnest, Clinton A. Taylor, Melanie H. Cobb, Benjamin P. Weaver
Summary: The authors found that the pool of non-phosphorylated p38 MAPK can modulate signaling to control growth, lysosome formation, and neuronal integrity. By altering the stoichiometry of non-phospho-p38, they enhanced PMK-1 signaling to promote tissue integrity and longevity. Their findings suggest that reducing the reservoir of non-phospho-p38 can enhance signaling without hyper-activation of stress response during aging.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Ana Martin-Vega, Melanie H. Cobb
Summary: The RAS-ERK pathway is crucial for various biological processes and its aberrant activation is implicated in diseases such as cancer. This review focuses on the structure, activation, regulation, and mutational frequency of the pathway, with an emphasis on ERK1/2. The significance of scaffold proteins in kinase localization and interaction dynamics is highlighted, along with potential therapeutic approaches in this field.
Article
Oncology
Wei Zou, Stephanie J. Yaung, Frederike Fuhlbrueck, Marcus Ballinger, Eric Peters, John F. Palma, David S. Shames, David Gandara, Yuqiu Jiang, Namrata S. Patil
Summary: In this study, the association between ctDNA MMPM levels at 6 weeks post-treatment and OS in advanced non-small-cell lung cancer patients treated with atezolizumab or docetaxel was investigated. The results suggest that ctDNA has the potential to serve as a noninvasive early liquid biopsy predictor for OS, highlighting the need for further studies to demonstrate its clinical utility.
JCO PRECISION ONCOLOGY
(2021)