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REVIEW
Ben Z Stanger, Geoffrey M Wahl
In the 160 years since Rudolf Virchow first postulated that neoplasia arises by the same law that regulated the embryonic development, scientists have come to recognize the striking overlap between the molecular and cellular programs used by cancers and embryos. Advances in cancer biology and molecular techniques have further highlighted the similarities between carcinogenesis and embryogenesis, where cellular growth, differentiation, motility, and intercellular cross talk are mediated by common drivers and regulatory networks...
October 13, 2023: Annual Review of Pathology
#2
MULTICENTER STUDY
Alexis F Guedon, Laure Ricard, Charlotte Laurent, Claire De Moreuil, Geoffrey Urbanski, Sophie Deriaz, Grigorios Gerotziafas, Ismail Elalamy, Alexandra Audemard, Francois Chasset, Sonia Alamowitch, Jérémie Sellam, Jean Jacques Boffa, Ariel Cohen, Clémentine Wahl, Noemie Abisror, François Maillot, Olivier Fain, Arsène Mekinian
INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by thrombosis (arterial, venous or small vessel) or obstetrical events and persistent antiphospholipid antibodies (aPL), according to the Sydney classification criteria. Many studies have performed cluster analyses among patients with primary APS and associated autoimmune disease, but none has focused solely on primary APS. We aimed to perform a cluster analysis among patients with primary APS and asymptomatic aPL carriers without any autoimmune disease, to assess prognostic value...
March 2023: RMD Open
#3
JOURNAL ARTICLE
Rui Tang, Emily G Shuldiner, Marcus Kelly, Christopher W Murray, Jess D Hebert, Laura Andrejka, Min K Tsai, Nicholas W Hughes, Mitchell I Parker, Hongchen Cai, Yao-Cheng Li, Geoffrey M Wahl, Roland L Dunbrack, Peter K Jackson, Dmitri A Petrov, Monte M Winslow
Oncogenic KRAS mutations occur in approximately 30% of lung adenocarcinoma. Despite several decades of effort, oncogenic KRAS-driven lung cancer remains difficult to treat, and our understanding of the regulators of RAS signalling is incomplete. Here to uncover the impact of diverse KRAS-interacting proteins on lung cancer growth, we combined multiplexed somatic CRISPR/Cas9-based genome editing in genetically engineered mouse models with tumour barcoding and high-throughput barcode sequencing. Through a series of CRISPR/Cas9 screens in autochthonous lung cancer models, we show that HRAS and NRAS are suppressors of KRASG12D -driven tumour growth in vivo and confirm these effects in oncogenic KRAS-driven human lung cancer cell lines...
January 2023: Nature Cell Biology
#4
JOURNAL ARTICLE
Zhichao Xu, Dong-Sung Lee, Sahaana Chandran, Victoria T Le, Rosalind Bump, Jean Yasis, Sofia Dallarda, Samantha Marcotte, Benjamin Clock, Nicholas Haghani, Chae Yun Cho, Kadir C Akdemir, Selene Tyndale, P Andrew Futreal, Graham McVicker, Geoffrey M Wahl, Jesse R Dixon
Higher-order chromatin structure is important for the regulation of genes by distal regulatory sequences1,2 . Structural variants (SVs) that alter three-dimensional (3D) genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer3 . However, only a small minority of SVs are associated with altered gene expression4,5 , and it remains unclear why certain SVs lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific rearrangements on oncogene activation...
December 7, 2022: Nature
#5
JOURNAL ARTICLE
Vikas B Gubbala, Nidhi Jytosana, Vincent Q Trinh, H Carlo Maurer, Razia F Naeem, Nikki K Lytle, Zhibo Ma, Steven Zhao, Wei Lin, Haiyong Han, Yu Shi, Tony Hunter, Pankaj K Singh, Kenneth P Olive, Marcus C B Tan, Susan M Kaech, Geoffrey M Wahl, Kathleen E DelGiorno
Background and Aims: Eicosanoids, oxidized fatty acids that serve as cell-signaling molecules, have been broadly implicated in tumorigenesis. Here, we aimed to identify eicosanoids associated with pancreatic tumorigenesis and the cell types responsible for their synthesis. Methods: We profiled normal pancreas and pancreatic ductal adenocarcinoma (PDAC) in mouse models and patient samples using mass spectrometry. We interrogated RNA sequencing datasets for eicosanoid synthase or receptor expression...
2022: Gastro Hep Adv
#6
JOURNAL ARTICLE
Ellen Langille, Khalid N Al-Zahrani, Zhibo Ma, Minggao Liang, Liis Uuskula-Reimand, Roderic Espin, Katie Teng, Ahmad Malik, Helga Bergholtz, Samah El Ghamrasni, Somaieh Afiuni-Zadeh, Ricky Tsai, Sana Alvi, Andrew Elia, YiQing Lu, Robin H Oh, Katelyn J Kozma, Daniel Trcka, Masahiro Narimatsu, Jeff C Liu, Thomas Nguyen, Seda Barutcu, Sampath K Loganathan, Rod Bremner, Gary D Bader, Sean E Egan, David W Cescon, Therese Sorlie, Jeffrey L Wrana, Hartland W Jackson, Michael D Wilson, Agnieszka K Witkiewicz, Erik S Knudsen, Miguel Angel Pujana, Geoffrey M Wahl, Daniel Schramek
Systematically investigating the scores of genes mutated in cancer and discerning disease drivers from inconsequential bystanders is a prerequisite for Precision Medicine but remains challenging. Here, we developed a somatic CRISPR/Cas9 mutagenesis screen to study 215 recurrent 'long-tail' breast cancer genes, which revealed epigenetic regulation as a major tumor suppressive mechanism. We report that components of the BAP1 and the COMPASS-like complexes, including KMT2C/D, KDM6A, BAP1 and ASXL1/2 ("EpiDrivers"), cooperate with PIK3CAH1047R to transform mouse and human breast epithelial cells...
September 15, 2022: Cancer Discovery
#7
JOURNAL ARTICLE
Kathleen DelGiorno, Zhibo Ma, Nikki Lytle, Bob Chen, Nidhi Jyotsana, Sammy Weiser Novak, Charles Cho, Leah Caplan, Olivia Ben-Levy, Abigail Neininger, Dylan Burnette, Vincent Trinh, Marcus Tan, Uri Manor, Jason Mills, James Goldenring, Ken Lau, Geoffrey Wahl
BACKGROUND AND AIMS: Despite years of research, mechanisms of pancreatic injury and healing remain poorly understood. Acute pancreatitis is a painful and debilitating condition; chronic pancreatitis may be asymptomatic, but greatly enhances the risk of pancreatic ductal adenocarcinoma (PDAC). Acinar to ductal metaplasia (ADM), or the transdifferentiation of digestive enzyme producing acinar cells to ductal cells, is an early event in both conditions. While ADM is thought to function in healing and regeneration, it also represents a first step in tumorigenesis, demonstrating the duplicitous nature of this inherent plasticity...
May 2022: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
#8
Yu Shi, Weina Gao, Nikki K Lytle, Peiwu Huang, Xiao Yuan, Amanda M Dann, Maya Ridinger-Saison, Kathleen E DelGiorno, Corina E Antal, Gaoyang Liang, Annette R Atkins, Galina Erikson, Huaiyu Sun, Jill Meisenhelder, Elena Terenziani, Gyunghwi Woo, Linjing Fang, Thom P Santisakultarm, Uri Manor, Ruilian Xu, Carlos R Becerra, Erkut Borazanci, Daniel D Von Hoff, Paul M Grandgenett, Michael A Hollingsworth, Mathias Leblanc, Sarah E Umetsu, Eric A Collisson, Miriam Scadeng, Andrew M Lowy, Timothy R Donahue, Tannishtha Reya, Michael Downes, Ronald M Evans, Geoffrey M Wahl, Tony Pawson, Ruijun Tian, Tony Hunter
No abstract text is available yet for this article.
November 30, 2021: Nature
#9
JOURNAL ARTICLE
Zhibo Ma, Nikki K Lytle, Bob Chen, Nidhi Jyotsana, Sammy Weiser Novak, Charles J Cho, Leah Caplan, Olivia Ben-Levy, Abigail C Neininger, Dylan T Burnette, Vincent Q Trinh, Marcus C B Tan, Emilee A Patterson, Rafael Arrojo E Drigo, Rajshekhar R Giraddi, Cynthia Ramos, Anna L Means, Ichiro Matsumoto, Uri Manor, Jason C Mills, James R Goldenring, Ken S Lau, Geoffrey M Wahl, Kathleen E DelGiorno
BACKGROUND & AIMS: Acinar to ductal metaplasia (ADM) occurs in the pancreas in response to tissue injury and is a potential precursor for adenocarcinoma. The goal of these studies was to define the populations arising from ADM, the associated transcriptional changes, and markers of disease progression. METHODS: Acinar cells were lineage-traced with enhanced yellow fluorescent protein (EYFP) to follow their fate post-injury. Transcripts of more than 13,000 EYFP+ cells were determined using single-cell RNA sequencing (scRNA-seq)...
February 2022: Gastroenterology
#10
REVIEW
Benjamin D Hamlington, Alex S Gardner, Erik Ivins, Jan T M Lenaerts, J T Reager, David S Trossman, Edward D Zaron, Surendra Adhikari, Anthony Arendt, Andy Aschwanden, Brian D Beckley, David P S Bekaert, Geoffrey Blewitt, Lambert Caron, Don P Chambers, Hrishikesh A Chandanpurkar, Knut Christianson, Beata Csatho, Richard I Cullather, Robert M DeConto, John T Fasullo, Thomas Frederikse, Jeffrey T Freymueller, Daniel M Gilford, Manuela Girotto, William C Hammond, Regine Hock, Nicholas Holschuh, Robert E Kopp, Felix Landerer, Eric Larour, Dimitris Menemenlis, Mark Merrifield, Jerry X Mitrovica, R Steven Nerem, Isabel J Nias, Veronica Nieves, Sophie Nowicki, Kishore Pangaluru, Christopher G Piecuch, Richard D Ray, David R Rounce, Nicole-Jeanne Schlegel, Hélène Seroussi, Manoochehr Shirzaei, William V Sweet, Isabella Velicogna, Nadya Vinogradova, Thomas Wahl, David N Wiese, Michael J Willis
Global sea level provides an important indicator of the state of the warming climate, but changes in regional sea level are most relevant for coastal communities around the world. With improvements to the sea-level observing system, the knowledge of regional sea-level change has advanced dramatically in recent years. Satellite measurements coupled with in situ observations have allowed for comprehensive study and improved understanding of the diverse set of drivers that lead to variations in sea level in space and time...
September 2020: Reviews of Geophysics
#11
JOURNAL ARTICLE
Kathleen E DelGiorno, Chi-Yeh Chung, Vera Vavinskaya, H Carlo Maurer, Sammy Weiser Novak, Nikki K Lytle, Zhibo Ma, Rajshekhar R Giraddi, Dezhen Wang, Linjing Fang, Razia F Naeem, Leonardo R Andrade, Wahida H Ali, Hubert Tseng, Crystal Tsui, Vikas B Gubbala, Maya Ridinger-Saison, Makoto Ohmoto, Galina A Erikson, Carolyn O'Connor, Maxim Nikolaievich Shokhirev, Nasun Hah, Yoshihiro Urade, Ichiro Matsumoto, Susan M Kaech, Pankaj K Singh, Uri Manor, Kenneth P Olive, Geoffrey M Wahl
BACKGROUND & AIMS: Development of pancreatic ductal adenocarcinoma (PDA) involves acinar to ductal metaplasia and genesis of tuft cells. It has been a challenge to study these rare cells because of the lack of animal models. We investigated the role of tuft cells in pancreatic tumorigenesis. METHODS: We performed studies with LSL-KrasG12D/+ ;Ptf1aCre/+ mice (KC; develop pancreatic tumors), KC mice crossed with mice with pancreatic disruption of Pou2f3 (KPouC mice; do not develop tuft cells), or mice with pancreatic disruption of the hematopoietic prostaglandin D synthase gene (Hpgds, KHC mice) and wild-type mice...
November 2020: Gastroenterology
#12
JOURNAL ARTICLE
John R Christin, Chunhui Wang, Chi-Yeh Chung, Yu Liu, Christopher Dravis, Wei Tang, Maja H Oktay, Geoffrey M Wahl, Wenjun Guo
Lineage plasticity is important for the development of basal-like breast cancer (BLBC), an aggressive cancer subtype. While BLBC is likely to originate from luminal progenitor cells, it acquires substantial basal cell features and contains a heterogenous collection of cells exhibiting basal, luminal, and hybrid phenotypes. Why luminal progenitors are prone to BLBC transformation and what drives luminal-to-basal reprogramming remain unclear. Here, we show that the transcription factor SOX9 acts as a determinant for estrogen-receptor-negative (ER- ) luminal stem/progenitor cells (LSPCs)...
June 9, 2020: Cell Reports
#13
JOURNAL ARTICLE
Yao-Cheng Li, Nikki K Lytle, Seth T Gammon, Luke Wang, Tikvah K Hayes, Margie N Sutton, Robert C Bast, Channing J Der, David Piwnica-Worms, Frank McCormick, Geoffrey M Wahl
HRAS, NRAS, and KRAS4A/KRAS4B comprise the RAS family of small GTPases that regulate signaling pathways controlling cell proliferation, differentiation, and survival. RAS pathway abnormalities cause developmental disorders and cancers. We found that KRAS4B colocalizes on the cell membrane with other RAS isoforms and a subset of prenylated small GTPase family members using a live-cell quantitative split luciferase complementation assay. RAS protein coclustering is mainly mediated by membrane association-facilitated interactions (MAFIs)...
June 2, 2020: Proceedings of the National Academy of Sciences of the United States of America
#14
JOURNAL ARTICLE
Michael A Badgley, Daniel M Kremer, H Carlo Maurer, Kathleen E DelGiorno, Ho-Joon Lee, Vinee Purohit, Irina R Sagalovskiy, Alice Ma, Jonathan Kapilian, Christina E M Firl, Amanda R Decker, Steve A Sastra, Carmine F Palermo, Leonardo R Andrade, Peter Sajjakulnukit, Li Zhang, Zachary P Tolstyka, Tal Hirschhorn, Candice Lamb, Tong Liu, Wei Gu, E Scott Seeley, Everett Stone, George Georgiou, Uri Manor, Alina Iuga, Geoffrey M Wahl, Brent R Stockwell, Costas A Lyssiotis, Kenneth P Olive
Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid reactive oxygen species (ROS). Oncogenic signaling elevates lipid ROS production in many tumor types and is counteracted by metabolites that are derived from the amino acid cysteine. In this work, we show that the import of oxidized cysteine (cystine) via system xC - is a critical dependency of pancreatic ductal adenocarcinoma (PDAC), which is a leading cause of cancer mortality. PDAC cells used cysteine to synthesize glutathione and coenzyme A, which, together, down-regulated ferroptosis...
April 3, 2020: Science
#15
JOURNAL ARTICLE
Kathleen E DelGiorno, Razia F Naeem, Linjing Fang, Chi-Yeh Chung, Cynthia Ramos, Natalie Luhtala, Carolyn O'Connor, Tony Hunter, Uri Manor, Geoffrey M Wahl
Chronic pancreatitis, a known risk factor for the development of pancreatic ductal adenocarcinoma (PDA), is a serious, widespread medical condition characterized by inflammation, fibrosis, and acinar to ductal metaplasia (ADM). ADM is a cell type transdifferentiation event where pancreatic acinar cells become ductal-like under conditions of injury or oncogenic mutation. Here, we show that chronic pancreatitis and ADM in genetically wild type mice results in the formation of a significant population of chemosensory tuft cells...
2020: Frontiers in Physiology
#16
JOURNAL ARTICLE
Margie N Sutton, Zhen Lu, Yao-Cheng Li, Yong Zhou, Tao Huang, Albert S Reger, Amy M Hurwitz, Timothy Palzkill, Craig Logsdon, Xiaowen Liang, Joe W Gray, Xiaolin Nan, John Hancock, Geoffrey M Wahl, Robert C Bast
Oncogenic RAS mutations drive cancers at many sites. Recent reports suggest that RAS dimerization, multimerization, and clustering correlate strongly with activation of RAS signaling. We have found that re-expression of DIRAS3, a RAS-related small GTPase tumor suppressor that is downregulated in multiple cancers, inhibits RAS/mitogen-activated protein kinase (MAPK) signaling by interacting directly with RAS-forming heteromers, disrupting RAS clustering, inhibiting Raf kinase activation, and inhibiting transformation and growth of cancer cells and xenografts...
December 10, 2019: Cell Reports
#17
JOURNAL ARTICLE
Chi-Yeh Chung, Zhibo Ma, Christopher Dravis, Sebastian Preissl, Olivier Poirion, Gidsela Luna, Xiaomeng Hou, Rajshekhar R Giraddi, Bing Ren, Geoffrey M Wahl
Technological improvements enable single-cell epigenetic analyses of organ development. We reasoned that high-resolution single-cell chromatin accessibility mapping would provide needed insight into the epigenetic reprogramming and transcriptional regulators involved in normal mammary gland development. Here, we provide a single-cell resource of chromatin accessibility for murine mammary development from the peak of fetal mammary stem cell (fMaSC) functional activity in late embryogenesis to the differentiation of adult basal and luminal cells...
October 8, 2019: Cell Reports
#18
JOURNAL ARTICLE
Kenan P Fears, Andrew Barnikel, Ann Wassick, Heonjune Ryou, Janna N Schultzhaus, Beatriz Orihuela, Jenifer M Scancella, Christopher R So, Kelli Z Hunsucker, Dagmar H Leary, Geoffrey Swain, Daniel Rittschof, Christopher M Spillmann, Kathryn J Wahl
Concerns about the bioaccumulation of toxic antifouling compounds have necessitated the search for alternative strategies to combat marine biofouling. Because many biologically essential minerals have deleterious effects on organisms at high concentration, one approach to preventing the settlement of marine foulers is increasing the local concentration of ions that are naturally present in seawater. Here, we used surface-active borate glasses as a platform to directly deliver ions (Na+ , Mg2+ and BO4 3- ) to the adhesive interface under acorn barnacles (Amphibalanus (=Balanus) amphitrite)...
October 28, 2019: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
#19
JOURNAL ARTICLE
Yu Shi, Weina Gao, Nikki K Lytle, Peiwu Huang, Xiao Yuan, Amanda M Dann, Maya Ridinger-Saison, Kathleen E DelGiorno, Corina E Antal, Gaoyang Liang, Annette R Atkins, Galina Erikson, Huaiyu Sun, Jill Meisenhelder, Elena Terenziani, Gyunghwi Woo, Linjing Fang, Thom P Santisakultarm, Uri Manor, Ruilian Xu, Carlos R Becerra, Erkut Borazanci, Daniel D Von Hoff, Paul M Grandgenett, Michael A Hollingsworth, Mathias Leblanc, Sarah E Umetsu, Eric A Collisson, Miriam Scadeng, Andrew M Lowy, Timothy R Donahue, Tannishtha Reya, Michael Downes, Ronald M Evans, Geoffrey M Wahl, Tony Pawson, Ruijun Tian, Tony Hunter
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology1,2 . The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance3-7 ...
May 2019: Nature
#20
JOURNAL ARTICLE
Christopher Dravis, Chi-Yeh Chung, Nikki K Lytle, Jaslem Herrera-Valdez, Gidsela Luna, Christy L Trejo, Tannishtha Reya, Geoffrey M Wahl
Cell state reprogramming during tumor progression complicates accurate diagnosis, compromises therapeutic effectiveness, and fuels metastatic dissemination. We used chromatin accessibility assays and transcriptional profiling during mammary development as an agnostic approach to identify factors that mediate cancer cell state interconversions. We show that fetal and adult basal cells share epigenetic features consistent with multi-lineage differentiation potential. We find that DNA-binding motifs for SOX transcription factors are enriched in chromatin that is accessible in stem/progenitor cells and inaccessible in differentiated cells...
September 10, 2018: Cancer Cell
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