Article
Oncology
Maureen Keller, Katarina Reis, Anders Hjerpe, Katalin Dobra, Pontus Aspenstrom
Summary: The cytoskeleton plays a crucial role in maintaining tissue homeostasis and its dysregulation is implicated in cancer progression, particularly in malignant mesothelioma. By studying the cytoskeletal dynamics and invasive properties of different malignant mesothelioma cell lines, it is possible to classify them into distinct categories which may aid in early diagnosis and development of new diagnostic tools. Additionally, the organization of key cytoskeletal components differs in highly malignant and invasive mesothelioma cells, with inactivation of the Hippo tumor suppressor pathway observed in invasive cells.
Article
Oncology
Balawant Kumar, Rizwan Ahmad, Giovanna A. Giannico, Roy Zent, Geoffrey A. Talmon, Raymond C. Harris, Peter E. Clark, Vinata Lokeshwar, Punita Dhawan, Amar B. Singh
Summary: The expression of claudin-2 is significantly decreased in PTE cells and ex-vivo cultured mouse kidneys subjected to dedifferentiation. Inhibition of claudin-2 induces mesenchymal plasticity and invasive mobility in these models. Overexpression of claudin-2 in RCC-derived cancer cells inhibits tumorigenic abilities, supporting a novel tumor-suppressive role of claudin-2 in RCC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Xigan He, Jinggui Chen, Jiamin Zhou, Anrong Mao, Weiqi Xu, Hongxu Zhu, Qi Pan, Yiming Zhao, Ning Zhang, Longrong Wang, Miao Wang, Zeyang Liu, Weiping Zhu, Lu Wang
Summary: This study identified a newly found lncRNA, EWSAT1, which plays a crucial role in hepatocellular carcinoma (HCC) metastasis. EWSAT1 is significantly upregulated in HCC and is associated with an aggressive phenotype and low patient survival. It promotes proliferation and metastasis of HCC cells by activating the transcription of cancer-related genes through the Hippo-YAP signaling pathway.
Article
Biochemistry & Molecular Biology
Xiaoyan Li, Zhengming Wu, Jing He, Yiting Jin, Chengyu Chu, Yun Cao, Fei Gu, Hongying Wang, Chenjian Hou, Xiuping Liu, Qiang Zou
Summary: The incidence of thyroid cancer is increasing globally, with poor prognosis associated with distant metastases. OGT and YAP play critical roles in papillary thyroid cancer, suggesting potential for targeted therapies.
Article
Biotechnology & Applied Microbiology
Zhuo Li, Zhiwen Lian, Jianchao Ma, Li Zhang, Xingji Lian, Shuangxin Liu, Jianteng Xie, Zhonglin Feng, Ting Lin, Hong Zhang, Xinling Liang
Summary: The axis formed by ITG beta 3, RhoA, and YAP plays a crucial role in podocyte injury induced by high glucose exposure. ITG beta 3 overexpression promotes podocyte injury by inhibiting the RhoA-YAP axis, while ITG beta 3 inhibition mitigates the ability of wound closure and apoptosis in podocytes under high glucose conditions.
Article
Oncology
Paola Matarrese, Rosa Vona, Barbara Ascione, Marco G. Paggi, Anna Maria Mileo
Summary: The study demonstrates that the interaction between HPV16 E7 and gelsolin promotes cytoskeleton rearrangement, leading to epithelial-mesenchymal transition and activating the HIPPO signaling pathway. This may play a role in the acquisition of a more aggressive phenotype in HPV16-transformed cells, providing potential therapeutic targets for HPV-related cancers.
Article
Urology & Nephrology
Francesca Fabretti, Nikolai Tschernoster, Florian Erger, Andrea Hedergott, Anja K. Buescher, Claudia Dafinger, Bjoern Reusch, Vincent K. Koentges, Stefan Kohl, Malte P. Bartram, Lutz Thorsten Weber, Holger Thiele, Janine Altmueller, Bernhard Schermer, Bodo B. Beck, Sandra Habbig
Summary: Through clinical and genetic characterization of 4 patients with FAT1-associated disease, novel FAT1 mutations were identified, expanding the spectrum of the disease. Analysis of patient-derived primary urinary epithelial cells revealed alterations in the Hippo signaling pathway with decreased YAP phosphorylation. The identified patients showed a diverse phenotype with missense mutations, while patients with truncating mutations displayed a more uniform and recognizable phenotype, suggesting altered Hippo signaling and de-repressed YAP activity as potential contributing factors in FAT1-associated renal disease.
KIDNEY INTERNATIONAL REPORTS
(2021)
Article
Biology
Arianna Pocaterra, Gloria Scattolin, Patrizia Romani, Cindy Ament, Silvia Ribback, Xin Chen, Matthias Evert, Diego F. Calvisi, Sirio Dupont
Summary: The study demonstrates that Fascin1 plays a key role in sustaining YAP activation in response to mechanical cues in the tumor environment, highlighting its potential as a clinical target for intrahepatic cholangiocarcinoma. Mechanically forces influence cancer progression by activating YAP through actomyosin. This finding suggests Fascin1 as a pro-oncogenic mechanism that could be targeted for therapeutic interventions in liver cancer.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biology
Daehee Hwang, Miju Kim, Soyeon Kim, Mi Ra Kwon, Ye-Seul Kang, Dahyun Kim, Ho-Chul Kang, Dae-Sik Lim
Summary: Contact inhibition is a crucial cellular phenomenon regulated by the Hippo signaling pathway, which controls cell growth and differentiation. Evidence suggests that WWP1 mono-ubiquitinates AMOTL2 and activates LATS at cell junctions under high cell density, emphasizing the importance of molecular mechanisms in responding to upstream cell density cues.
LIFE SCIENCE ALLIANCE
(2021)
Article
Physiology
Kathryn E. E. Haley, Mustafa Elshani, In Hwa Um, Cameron Bell, Peter D. D. Caie, David J. J. Harrison, Paul A. A. Reynolds
Summary: Podocyte loss is crucial in glomerular disease pathogenesis. The study found a significant decrease in podocyte density in late grade Diabetic Nephropathy, potentially linked to early cytoplasmic translocation of YAP.
FRONTIERS IN PHYSIOLOGY
(2021)
Correction
Biochemistry & Molecular Biology
Xiao Zheng, Lujun Chen, You Zhou, Qi Wang, Zhuojun Zheng, Bin Xu, Chen Wu, Qi Zhou, Wenwei Hu, Changping Wu, Jingting Jiang
Summary: The paper has published an amendment which can be accessed through the original article.
Article
Multidisciplinary Sciences
Xu Li, Shu Zhuo, Ting Zhuang, Yong Suk Cho, Guojin Wu, Yuchen Liu, Kun Mu, Kai Zhang, Peng Su, Yingzi Yang, Cheng Cheng Zhang, Jian Zhu, Jin Jiang
Summary: Hippo signaling restricts tissue growth by inhibiting YAP, which also functions as a tumor suppressor in ER+ breast cancer by interfering with the TEAD-ERα signaling axis.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lingquan Wang, Wei Xu, Yu Mei, Xufeng Wang, Wentao Liu, Zhenggang Zhu, Zhentian Ni
Summary: This study found that CHRDL2 is abnormally upregulated in gastric cancer and is associated with tumor progression and poor patient prognosis. CHRDL2 overexpression promotes proliferation and cell cycle transition of gastric cancer cells, and it plays a key role by activating the YAP/TAZ pathway.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Cell Biology
Lan Jin, Yunhe Chen, Dan Cheng, Zhikai He, Xinyi Shi, Boyu Du, Xueyan Xi, Yujing Gao, Yang Guo
Summary: Colorectal cancer is a highly aggressive and lethal cancer, with autophagy playing a complex role in its pathobiology. The transcriptional coactivator YAP has been found to negatively regulate autophagy in CRC cells, promoting tumor progression by upregulating the apoptosis-inhibitory protein Bcl-2 through TEAD interaction, thereby suppressing autophagy-related cell death. Targeting the YAP/Bcl-2 pathway may hold promise as a potential therapeutic strategy against CRC.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Yuegui Guo, Zhehui Zhu, Zhenyu Huang, Long Cui, Wei Yu, Wanjin Hong, Zhaocai Zhou, Peng Du, Chen-Ying Liu
Summary: In this study, the researchers found that HHEX acts as a positive regulator of YAP/TEAD, promoting colorectal tumorigenesis. HHEX interacts with and stabilizes the YAP/TEAD complex, coregulating the expression of YAP/TEAD target genes. CK2 phosphorylates HHEX to enhance its interaction with TEAD4. The elevated expression of HHEX is associated with poor prognosis of CRC patients.
NATURE COMMUNICATIONS
(2022)
Review
Pathology
Swati Satturwar, Mary Fowkes, Carol Farver, Allecia M. Wilson, Albino Eccher, Ilaria Girolami, Elisabet Pujadas, Clare Bryce, Fadi Salem, Siraj M. El Jamal, Alberto Paniz-Mondolfi, Bruce Petersen, Ronald E. Gordon, Jason Reidy, Filippo Fraggetta, Desiree A. Marshall, Liron Pantanowitz
Summary: Autopsy findings from COVID-19 and SARS-CoV-1 cases suggest that DAD is more common in SARS-CoV-1, while hepatic necrosis, splenic necrosis, and white pulp depletion are more frequently associated with SARS-CoV-1 compared to COVID-19 cases.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2021)
Article
Endocrinology & Metabolism
Lili Chan, Girish N. Nadkarni, Fergus Fleming, James R. McCullough, Patricia Connolly, Gohar Mosoyan, Fadi El Salem, Michael W. Kattan, Joseph A. Vassalotti, Barbara Murphy, Michael J. Donovan, Steven G. Coca, Scott M. Damrauer
Summary: Predicting progression in diabetic kidney disease is crucial for improving outcomes. The machine-learned prognostic risk score KidneyIntelX showed better performance in predicting kidney outcomes compared to the KDIGO and clinical models.
Article
Pathology
Siraj M. El Jamal, Elisabet Pujadas, Irene Ramos, Clare Bryce, Zachary M. Grimes, Fatima Amanat, Nadejda M. Tsankova, Zarmeen Mussa, Sara Olson, Fadi Salem, Lisa Miorin, Teresa Aydillo, Michael Schotsaert, Randy A. Albrecht, Wen-Chun Liu, Nada Marjanovic, Nancy Francoeur, Robert Sebra, Stuart C. Sealfon, Adolfo Garcia-Sastre, Mary Fowkes, Carlos Cordon-Cardo, William H. Westra
Summary: In most cases where patients die from COVID-19-related organ failure, SARS-CoV-2 is not detectable in tissues. Even in severely damaged lungs, viral RNA or proteins were only detected in a minority of cases. This suggests that viral infection mainly triggers proinflammatory responses in multiple organs, rather than directly causing sustained tissue damage.
Article
Pathology
Clare Bryce, Zachary Grimes, Elisabet Pujadas, Sadhna Ahuja, Mary Beth Beasley, Randy Albrecht, Tahyna Hernandez, Aryeh Stock, Zhen Zhao, Mohamed Rizwan AlRasheed, Joyce Chen, Li Li, Diane Wang, Adriana Corben, G. Kenneth Haines, William H. Westra, Melissa Umphlett, Ronald E. Gordon, Jason Reidy, Bruce Petersen, Fadi Salem, Maria Isabel Fiel, Siraj M. El Jamal, Nadejda M. Tsankova, Jane Houldsworth, Zarmeen Mussa, Brandon Veremis, Emilia Sordillo, Melissa R. Gitman, Michael Nowak, Rachel Brody, Noam Harpaz, Miriam Merad, Sacha Gnjatic, Wen-Chun Liu, Michael Schotsaert, Lisa Miorin, Teresa A. Aydillo Gomez, Irene Ramos-Lopez, Adolfo Garcia-Sastre, Ryan Donnelly, Patricia Seigler, Calvin Keys, Jennifer Cameron, Isaiah Moultrie, Kae-Lynn Washington, Jacquelyn Treatman, Robert Sebra, Jeffrey Jhang, Adolfo Firpo, John Lednicky, Alberto Paniz-Mondolfi, Carlos Cordon-Cardo, Mary E. Fowkes
Summary: The study reports the first 100 COVID-19-positive autopsies performed in New York City, revealing widespread effects including diffuse alveolar damage, large pulmonary emboli, microthrombi in multiple organ systems, and presence of the virus in samples. Laboratory results showed elevated inflammatory markers, abnormal coagulation values, and increased cytokines.
Article
Urology & Nephrology
Fadi Salem, Laura Perin, Sargis Sedrakyan, Andrea Angeletti, Gian Marco Ghiggeri, Maria Cristina Coccia, Marty Ross, Miguel Fribourg, Paolo Cravedi
Summary: The application of spatial transcriptomics in kidney transplant biopsies allows for the study of variability between different regions in acute cellular rejection, revealing new pathogenic mechanisms related to the graft response to alloimmune attack and providing new therapeutic targets for acute cellular rejection and other kidney diseases with a focal nature.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Camille Nicolas Frank, Xiaogang Hou, Astgik Petrosyan, Valentina Villani, Rui Zhao, Joshua R. Hansen, Geremy Clair, Fadi Salem, Roger E. De Filippo, Paolo Cravedi, Kevin Lemley, Laura Perin
Summary: In the Alport model of progressive CKD, the distribution of podocyte cell cycle is altered, suggesting potential approaches for the treatment of glomerular diseases characterized by podocytopenia.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Fadi Salem, Xue Zhu Li, Judy Hindi, Nitzy Munoz Casablanca, Fang Zhong, Siraj M. El Jamal, Mohamed Rizwan Haroon Al Rasheed, Li Li, Kyung Lee, Lili Chan, John Cijiang He
Summary: This study suggests that serine phosphorylation of STAT3, instead of tyrosine phosphorylation, is commonly activated in the kidney of patients with COVID-19.
JOURNAL OF NEPHROLOGY
(2022)
Article
Urology & Nephrology
Zhengzi Yi, Fadi Salem, Madhav C. Menon, Karen Keung, Caixia Xi, Sebastian Hultin, M. Rizwan Haroon Al Rasheed, Li Li, Fei Su, Zeguo Sun, Chengguo Wei, Weiqing Huang, Samuel Fredericks, Qisheng Lin, Khadija Banu, Germaine Wong, Natasha M. Rogers, Samira Farouk, Paolo Cravedi, Meena Shingde, R. Neal Smith, Ivy A. Rosales, Philip J. O'Connell, Robert B. Colvin, Barbara Murphy, Weijia Zhang
Summary: This study utilized deep-learning to objectively and quantitatively assess the pathological lesions in kidney transplant recipients. The findings showed that this method accurately detected and quantified the lesions, and demonstrated superior predictive ability for post-transplant graft loss. This research has significant implications for medical prediction and monitoring of transplant recipients.
KIDNEY INTERNATIONAL
(2022)
Article
Urology & Nephrology
Jenelle Cocorpus, Megan M. Hager, Corinne Benchimol, Vanesa Bijol, Fadi Salem, Sumit Punj, Laura Castellanos, Pamela Singer, Christine B. Sethna, Abby Basalely
Summary: Alport syndrome, a hereditary kidney disease, can be diagnosed more accurately through genetic testing. This study reports a case of a Mexican family with a COL4A4 variant, highlighting the importance of family genetic patterns and comprehensive medical history in variant interpretation.
Editorial Material
Urology & Nephrology
Justina Ray, Steven Smith, Sean Lefferts, Kristin Meliambro, Fadi Salem, Kirk N. Campbell
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Medicine, Research & Experimental
Kristin Meliambro, Yanfeng Yang, Marina de Cos, Estefania Rodriguez Ballestas, Caroline Malkin, Jonathan Haydak, John R. Lee, Fadi Salem, Laura H. Mariani, Ronald E. Gordon, John M. Basgen, Huei Hsun Wen, Jia Fu, Evren U. Azeloglu, John Cijiang He, Jenny S. Wong, Kirk N. Campbell
Summary: Despite progress in identifying mediators of podocyte injury, mechanisms and therapies for podocyte loss remain poorly understood. This study investigated the role of WWC1/KIBRA in podocyte injury and found that overexpression of KIBRA promoted cytoplasmic localization of YAP and altered podocyte structure. Transgenic mice with WWC1 overexpression were more susceptible to glomerular injury, and clinical data showed that glomerular WWC1 expression correlated with poor renal survival in patients with glomerular diseases. These findings emphasize the importance of KIBRA/YAP signaling in regulating podocyte integrity and suggest KIBRA-mediated injury as a potential therapeutic target.
Article
Engineering, Biomedical
Tess K. Fallon, Merve Zuvin, Alan D. Stern, Nanditha Anandakrishnan, Ilse S. Daehn, Evren U. Azeloglu
Summary: Microphysiological systems incorporating membranes with human cells can mimic biological filtration barriers, providing a platform for studying cellular filtration processes and drug effects. This study presents an affordable, open-source platform for real-time monitoring of filtration status, capable of detecting concentrations of target molecules and suitable for continuous operation.
ANNALS OF BIOMEDICAL ENGINEERING
(2023)
Article
Urology & Nephrology
Kelly L. Budge, Alberto Verlato, Sofia Bin, Fadi E. Salem, Laura Perin, Gaetano La Manna, Gianluigi Zaza, Enrico Fiaccadori, Chiara Cantarelli, Paolo Cravedi
Summary: Complement activation plays a major role in membranous nephropathy (MN), and podocyte-expressed complement regulators, including decay-accelerating factor (DAF), are involved in disease pathophysiology. In a mouse model of MN, DAF deletion resulted in increased complement activation and disease severity, while treatment with a C3aR antagonist reduced disease severity. Evidence suggests that IgG-cBSA immune complex formation activates complement through the classical pathway. These findings may have translational implications for the treatment of patients with MN, especially with complement targeting therapies.
Article
Medicine, General & Internal
Dawn Maldonado, Justina Ray, XiongBin Lin, Fadi Salem, Maritza Brown, Ishita Bansal
Summary: We report a case of dialysis dependence in a patient with COVID-19-associated nephropathy (COVAN) who had minimal respiratory manifestations. This case highlights the importance of evaluating the severity of COVID-19 beyond oxygen requirements.
JOURNAL OF INVESTIGATIVE MEDICINE HIGH IMPACT CASE REPORTS
(2022)
Article
Medicine, Research & Experimental
Zhongyang Zhang, Zeguo Sun, Jia Fu, Qisheng Lin, Khadija Banu, Kinsuk Chauhan, Marina Planoutene, Chengguo Wei, Fadi Salem, Zhengzi Yi, Ruijie Liu, Paolo Cravedi, Haoxiang Cheng, Ke Hao, Philip J. O'Connell, Shuta Ishibe, Weijia Zhang, Steven G. Coca, Ian W. Gibson, Robert B. Colvin, John Cijiang He, Peter S. Heeger, Barbara Murphy, Madhav C. Menon
Summary: The presence of recipient APOL1 risk alleles is independently associated with transplant outcomes, especially in African American and Hispanic recipients, potentially impacting immune response. This finding suggests broader implications for immune-mediated injury to native kidneys.
JOURNAL OF CLINICAL INVESTIGATION
(2021)