Article
Biochemistry & Molecular Biology
Sonja Srdanovic, Madita Wolter, Chi H. Trinh, Christian Ottmann, Stuart L. Warriner, Andrew J. Wilson
Summary: p53 plays a critical role in regulating diverse biological processes and is negatively regulated by hDMX and hDM2. Previous studies have identified 14-3-3 proteins as potential regulators of the interaction between hDMX or hDM2 and p53. This study characterizes the biophysical and structural features of the interaction between 14-3-3 and hDMX or hDM2, providing insights for future drug discovery efforts.
Article
Multidisciplinary Sciences
Shichao Lin, Kun Yin, Yingkun Zhang, Fanghe Lin, Xiaoyong Chen, Xi Zeng, Xiaoxu Guo, Huimin Zhang, Jia Song, Chaoyong Yang
Summary: In this study, a method called Well-TEMP-seq was developed, which is a high-throughput, cost-effective, accurate, and efficient approach for profiling the temporal dynamics of single-cell gene expression. By combining metabolic RNA labeling with single-cell RNA sequencing, Well-TEMP-seq can distinguish newly transcribed RNAs from pre-existing RNAs in thousands of single cells. The application of this method to colorectal cancer cells exposed to the DNA demethylating drug 5-AZA-CdR revealed its unbiased capturing of RNA dynamics and superior performance compared to splicing-based RNA velocity method.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Tushar Kamath, Abdulraouf Abdulraouf, S. J. Burris, Jonah Langlieb, Vahid Gazestani, Naeem M. Nadaf, Karol Balderrama, Charles Vanderburg, Evan Z. Macosko
Summary: In this study, single-cell genomics was used to analyze thousands of human dopamine neurons and identify a unique population susceptible to Parkinson's disease, which was enriched for genetic risk.
NATURE NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Srijata Mukherjee, Gouranga Saha, Neeladri Sekhar Roy, Gitashri Naiya, Mrinal K. Ghosh, Siddhartha Roy
Summary: HDM2 is an important E3 ubiquitin ligase, regulating many proliferation-related pathways and serving as one of the primary regulators of p53. USP7, a deubiquitinase, plays a key role in the regulation of both p53 and HDM2, forming a small regulatory network with them. This network has emerged as an important drug target.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Oncology
Sebastian Bauer, George D. Demetri, Ensar Halilovic, Reinhard Dummer, Christophe Meille, Daniel S. W. Tan, Nelson Guerreiro, Astrid Jullion, Stephane Ferretti, Sebastien Jeay, Laurence Van Bree, Florence Hourcade-Potelleret, Jens U. Wuerthner, Claire Fabre, Philippe A. Cassier
Summary: The study aimed to assess the safety, MTD, PK/PD, and preliminary antitumor activity of CGM097 in advanced solid tumor patients. PK/PD models were used to guide dose regimen selection and predict response to CGM097. Despite limited activity, insights were provided on dosing optimization for next-generation HDM2 inhibitors to mitigate hematologic toxicity.
BRITISH JOURNAL OF CANCER
(2021)
Article
Multidisciplinary Sciences
Tsinat Berhane, Anja Holm, Kasper Thystrup Karstensen, Andreas Petri, Mirolyuba Simeonova Ilieva, Henrik Krarup, Mogens Vyberg, Marianne Bengtson Lovendorf, Sakari Kauppinen
Summary: In this study, it was found that the overexpression of lncRNA PURPL in HCC inhibits cell proliferation, induces apoptosis, and increases the sensitivity of HCC cells to the chemotherapeutic agent doxorubicin.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Shizhe Yu, Haoren Wang, Lingpeng Yang, Yingxue Yan, Qiang Cai, Duo Ma, Long Jiang, Zehai Gao, Zhiyong Yu, Zongping Xia
Summary: The comprehensive study of the spatial-cellular anatomy of the human liver is crucial for understanding the cellular origins of liver disease. In this study, spatial transcriptomics were conducted on normal human liver tissue sections, providing detailed transcriptional information on liver zonation. A total of 6581 high-quality spots from normal livers were analyzed, mainly consisting of hepatocytes, which were classified into four sub-groups. These data serve as a reliable reference for studying the spatial heterogeneity of liver lobules.
Article
Chemistry, Medicinal
Michael H. Reutershan, Michelle R. Machacek, Michael D. Altman, Stephane Bogen, Mingmei Cai, Carolyn Cammarano, Dapeng Chen, Matthew Christopher, John Cryan, Pierre Daublain, Xavier Fradera, Prasanthi Geda, Peter Goldenblatt, Armetta D. Hill, Raymond A. Kemper, Victoria Kutilek, Chaomin Li, Michelle Martinez, Mark McCoy, Latha Nair, Weidong Pan, Christopher F. Thompson, Giovanna Scapin, Manami Shizuka, Marianne L. Spatz, Dietrich Steinhuebel, Binyuan Sun, Matthew E. Voss, Xiao Wang, Liping Yang, Tammie C. Yeh, Isabelle Dussault, C. Gary Marshall, B. Wesley Trotter
Summary: Identifying low-dose, low-molecular-weight, drug-like inhibitors of protein-protein interactions is challenging yet important. By leveraging known binding hot spots and biostructural information, researchers successfully optimized a novel purine carboxylic acid-derived inhibitor into a series of low-projected dose inhibitors with favorable pharmacokinetic and physical properties, leading to the discovery of a highly potent, selective, and low-molecular-weight inhibitor suitable for clinical investigation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Stephanie M. Zimmerman, Robin Fropf, Bridget R. Kulasekara, Maddy Griswold, Oliver Appelbe, Arya Bahrami, Rich Boykin, Derek L. Buhr, Kit Fuhrman, Margaret L. Hoang, Quoc Huynh, Lesley Isgur, Andrew Klock, Alecksandr Kutchma, Alexa E. Lasley, Yan Liang, Jill McKay-Fleisch, Jeffrey S. Nelson, Karen Nguyen, Erin Piazza, Aric Rininger, Daniel R. Zollinger, Michael Rhodes, Joseph M. Beechem
Summary: Emerging spatial profiling technology allows high-plex molecular profiling in biological tissues while preserving the spatial and morphological context of gene expression. By expanding the chemistry for the Digital Spatial Profiling platform, researchers have successfully quantified whole transcriptomes in human and mouse tissues, enabling applications in cancer research, molecular pathology, and developmental biology.
Article
Multidisciplinary Sciences
Johannes Bloehdorn, Andrejs Braun, Amaro Taylor-Weiner, Billy Michael Chelliah Jebaraj, Sandra Robrecht, Julia Krzykalla, Heng Pan, Adam Giza, Gulnara Akylzhanova, Karlheinz Holzmann, Annika Scheffold, Harvey E. Johnston, Ru-Fang Yeh, Tetyana Klymenko, Eugen Tausch, Barbara Eichhorst, Lars Bullinger, Kirsten Fischer, Martin Weisser, Tadeusz Robak, Christof Schneider, John Gribben, Lekh N. Dahal, Mathew J. Carter, Olivier Elemento, Dan A. Landau, Donna S. Neuberg, Mark S. Cragg, Axel Benner, Michael Hallek, Catherine J. Wu, Hartmut Doehner, Stephan Stilgenbauer, Daniel Mertens
Summary: Understanding the complex genomics of chronic lymphocytic leukemia (CLL) has revealed distinct molecular subtypes with different prognostic implications, involving activation of epithelial-mesenchymal-transition (EMT) programs and genomic instability. Targeting these molecular subclasses may lead to new treatment strategies for CLL.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Yan Wu, Lingfeng Xue, Wen Huang, Minghua Deng, Yihan Lin
Summary: This paper proposes an alternative approach for analyzing transcription factor activities using the expression levels of unmatured mRNAs of target genes. By utilizing this method, researchers can decode the temporal control of transcription factor activities during key biological processes and gain insights into the regulatory principles of dynamic cellular processes. The results also reveal two temporally opposing modules of transcription factors that play important roles in immune responses. Overall, this approach provides a valuable tool for understanding and studying transcription factor activities in dynamic cellular processes.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Oncology
Vincent Vuaroqueaux, Hans R. Hendriks, Hoor Al-Hasani, Anne-Lise Peille, Samayita Das, Heinz-Herbert Fiebig
Summary: MI-773, a small-molecule inhibitor of MDM2, demonstrates pronounced selectivity and moderate potency against a variety of tumors in vitro, particularly in melanoma, sarcoma, renal and gastric cancers, leukemia, and lymphoma. Its activity is primarily associated with cell lines with wild type TP53 and is predicted by specific biomarkers related to the p53 pathway.
NPJ PRECISION ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Xin Chen, Tianqi Liu, Jianqi Wu, Chen Zhu, Gefei Guan, Cunyi Zou, Qing Guo, Xiaolin Ren, Chen Li, Peng Cheng, Wen Cheng, Anhua Wu
Summary: This study extracted genetic and epigenetic features of TP53mut tumors and identified five different subtypes of TP53mut patients. These subtypes have distinct characteristics in terms of genomic alterations, clinical relevance, microenvironment dysregulation, and potential therapeutics. Among the subtypes, COCA3 was identified as having the worst prognosis, while olaparib showed promising therapeutic efficacy.
Article
Biochemistry & Molecular Biology
Ferhat Alkan, Oscar G. Wilkins, Santiago Hernandez-Perez, Sofia Ramalho, Joana Silva, Jernej Ule, William J. Faller
Summary: Recent studies have identified multiple mechanisms that contribute to the heterogeneity in ribosomal composition, and have developed a new method, called dripARF, to study this phenomenon. This method uses Ribosome Profiling (Ribo-seq) data to detect differential protein incorporation into the ribosome by combining "waste" rRNA fragment data with the known 3D structure of the human ribosome. The results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new tool to study this phenomenon.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Li Ding, Yujie Xu, Lin Xu, Chenhong Zhao, Zhiping Zhang, Jie Zhang, Kai Liao, Yuerou Chen, Jingwen Li, Xinyu Mei, Xinyue Zhang
Summary: This study reveals that PDCD11, a nucleolar protein, has an extra-nucleolar localization and regulates the G2/M checkpoint in colorectal cancer cells. PDCD11 interacts with p53 and HDM2 to facilitate p53 degradation, leading to downregulation of p53 and upregulation of CDK1 for G2/M transition. PDCD11 also independently upregulates CDC25C to dephosphorylate CDK1. Downregulation of PDCD11 inhibits cancer cell growth and increases sensitivity to DNA damage signals, suggesting its importance as a driving factor and potential target for colorectal cancer treatment.
Article
Biochemical Research Methods
Keerti Potluri, Ahmed Mahas, Michael N. Kent, Sameep Naik, Michael Markey
ANALYTICAL BIOCHEMISTRY
(2015)
Article
Oncology
Ahmed Mahas, Keerti Potluri, Michael N. Kent, Sameep Naik, Michael Markey
Article
Biochemistry & Molecular Biology
Sapna Varia, Divya Cheedu, Michael Markey, Keshia Torres-Shafer, Vishnu Priya Battini, Athanasios Bubulya, Paula A. Bubulya
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2017)
Article
Obstetrics & Gynecology
Logan M. Havemann, David R. Cool, Pascal Gagneux, Michael P. Markey, Jerome L. Yaklic, Rose A. Maxwell, Ashvin Iyer, Steven R. Lindheim
JOURNAL OF LOWER GENITAL TRACT DISEASE
(2017)
Article
Developmental Biology
Eugene Matthew P. Almazan, Sydney L. Lesko, Michael P. Markey, Labib Rouhana
DEVELOPMENTAL BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Michael P. Markey
FRONTIERS IN BIOSCIENCE-LANDMARK
(2011)
Article
Cell Biology
Alok Sharma, Michael Markey, Keshia Torres-Munoz, Sapna Varia, Madhavi Kadakia, Athanasios Bubulya, Paula A. Bubulya
JOURNAL OF CELL SCIENCE
(2011)
Article
Multidisciplinary Sciences
Pooja Mandke, Nicholas Wyatt, Jillian Fraser, Benjamin Bates, Steven J. Berberich, Michael P. Markey
Article
Multidisciplinary Sciences
Marjorie S. Morgan, Larry G. Arlian, Michael P. Markey
Article
Cell Biology
Minyi Chen, Amanda K. Myers, Michael P. Markey, Weiwen Long
JOURNAL OF CELLULAR PHYSIOLOGY
(2019)
Article
Dermatology
Abdullah Alatawi, SoonJye Kho, Michael P. Markey
Summary: The activity of p53 is lost in cancer, including melanoma, where the intact p53 gene is kept inactive through interaction with inhibitory proteins rather than direct mutation. The inhibitors MDM2 and MDM4 are frequently overexpressed in melanoma, with splicing changes in MDM4 occurring frequently and early in melanomagenesis. These splicing changes should be taken into consideration when designing therapeutic inhibitors of MDM2/4 proteins for melanoma.
JOURNAL OF SKIN CANCER
(2021)
Article
Multidisciplinary Sciences
Ashley Turner, Michael Markey, Peter Le, Ali Reiter, Cyndy Cox, Stacy Simmons, M. B. Rao, Lorenna Altman, Kermit Davis, Dustin Huber, Jonathan S. Dufour, William Marras, Amit Bhattacharya
Summary: This study aimed to quantify the physiological effects of motion sickness on static balance and determine the associated genetic predictors. The findings revealed significant effects of motion sickness on postural balance and differential expression of small ribonucleic acids in individuals with long stimulus survival times.
Article
Biochemistry & Molecular Biology
Paul Wong, M. Markey, C. M. Rapp, R. M. Darrow, A. Ziesel, D. T. Organisciak
Meeting Abstract
Oncology
Prithy C. Martis, Atira Dudley, Melissa A. Laramore, Hunter L. Gazda, Michael P. Markey, Barry H. Smith, Lawrence S. Gazda