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Your search keyword '"Justina Almodovar"' showing total 4 results
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4 results on '"Justina Almodovar"'

1. Systems-level analyses of protein-protein interaction network dysfunctions via epichaperomics identify cancer-specific mechanisms of stress adaptation

Author

Anna Rodina, Chao Xu, Chander S. Digwal, Suhasini Joshi, Yogita Patel, Anand R. Santhaseela, Sadik Bay, Swathi Merugu, Aftab Alam, Pengrong Yan, Chenghua Yang, Tanaya Roychowdhury, Palak Panchal, Liza Shrestha, Yanlong Kang, Sahil Sharma, Justina Almodovar, Adriana Corben, Mary L. Alpaugh, Shanu Modi, Monica L. Guzman, Teng Fei, Tony Taldone, Stephen D. Ginsberg, Hediye Erdjument-Bromage, Thomas A. Neubert, Katia Manova-Todorova, Meng-Fu Bryan Tsou, Jason C. Young, Tai Wang, and Gabriela Chiosis

Subjects
Science
Abstract

Abstract Systems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based ‘omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights. As proof-of-principle, we derive systems-level insight into PPI dysfunctions of cancer cells which enabled the discovery of a context-dependent mechanism by which cancer cells enhance the fitness of mitotic protein networks. Importantly, our systems levels analyses support the use of epichaperome chemical binders as therapeutic strategies aimed at normalizing PPI networks.

Published
2023
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2. Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer

Author

Suhasini Joshi, Erica DaGama Gomes, Tai Wang, Adriana Corben, Tony Taldone, Srinivasa Gandu, Chao Xu, Sahil Sharma, Salma Buddaseth, Pengrong Yan, Lon Yin L. Chan, Askan Gokce, Vinagolu K. Rajasekhar, Lisa Shrestha, Palak Panchal, Justina Almodovar, Chander S. Digwal, Anna Rodina, Swathi Merugu, NagaVaraKishore Pillarsetty, Vlad Miclea, Radu I. Peter, Wanyan Wang, Stephen D. Ginsberg, Laura Tang, Marissa Mattar, Elisa de Stanchina, Kenneth H. Yu, Maeve Lowery, Olivera Grbovic-Huezo, Eileen M. O’Reilly, Yelena Janjigian, John H. Healey, William R. Jarnagin, Peter J. Allen, Chris Sander, Hediye Erdjument-Bromage, Thomas A. Neubert, Steven D. Leach, and Gabriela Chiosis

Subjects
Biology (General), QH301-705.5
Abstract

Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.

Published
2021
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3. Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system

Author

Alexander Bolaender, Danuta Zatorska, Huazhong He, Suhasini Joshi, Sahil Sharma, Chander S. Digwal, Hardik J. Patel, Weilin Sun, Brandon S. Imber, Stefan O. Ochiana, Maulik R. Patel, Liza Shrestha, Smit. K. Shah, Shuo Wang, Rashad Karimov, Hui Tao, Pallav D. Patel, Ananda Rodilla Martin, Pengrong Yan, Palak Panchal, Justina Almodovar, Adriana Corben, Andreas Rimner, Stephen D. Ginsberg, Serge Lyashchenko, Eva Burnazi, Anson Ku, Teja Kalidindi, Sang Gyu Lee, Milan Grkovski, Bradley J. Beattie, Pat Zanzonico, Jason S. Lewis, Steve Larson, Anna Rodina, Nagavarakishore Pillarsetty, Viviane Tabar, Mark P. Dunphy, Tony Taldone, Fumiko Shimizu, and Gabriela Chiosis

Subjects
Science
Abstract

Here, the authors show structural, biochemical, and functional insights into the discovery of epichaperome‐ directed chemical probes for use in central nervous system diseases. Probes emerging from this work have translated to human clinical studies in Alzheimer’s disease and cancer.

Published
2021
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4. Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer

Author

Chander Singh Digwal, Peter J. Allen, Thomas A. Neubert, Swathi Merugu, Eileen M. O'Reilly, Wanyan Wang, Lon Yin L. Chan, Vinagolu K. Rajasekhar, Suhasini Joshi, Tony Taldone, Nagavarakishore Pillarsetty, Olivera Grbovic-Huezo, Erica DaGama Gomes, Maeve A. Lowery, Srinivasa Gandu, Anna Rodina, Stephen D. Ginsberg, Gabriela Chiosis, Vlad Miclea, Elisa de Stanchina, Laura H. Tang, Palak Panchal, Chris Sander, Lisa Shrestha, Kenneth H. Yu, Chao Xu, Steven D. Leach, Hediye Erdjument-Bromage, Marissa Mattar, Pengrong Yan, Radu I Peter, John H. Healey, Adriana D. Corben, Justina Almodovar, Sahil Sharma, William R. Jarnagin, Yelena Y. Janjigian, Salma Buddaseth, Tai Wang, and Askan Gokce

Subjects
QH301-705.5, Cell, Chemical biology, Medicine (miscellaneous), Biology, Interactome, General Biochemistry, Genetics and Molecular Biology, Article, Protein–protein interaction, Epigenesis, Genetic, Mice, Neoplasms, Protein Interaction Mapping, medicine, Animals, Humans, Protein Interaction Maps, Biology (General), Genome, Cancer, Hyperconnectivity, medicine.disease, Networks and systems biology, Cancer therapeutic resistance, Signalling, medicine.anatomical_structure, Cancer cell, Heterografts, Female, General Agricultural and Biological Sciences, Neuroscience, Molecular Chaperones, Signal Transduction
Abstract

Cancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours. Further, we can essentially force tumours into interactome hyperconnectivity and maximal protein-protein interaction capacity, a state whereby no rebound pathways can be deployed and where alternative signalling is supressed. This approach therefore primes interactomes to enhance vulnerability and improve treatment efficacy, enabling therapeutics with traditionally poor performance to become highly efficacious. These findings provide proof-of-principle for a paradigm to overcome drug resistance through pharmacologic manipulation of proteome-wide protein-protein interaction networks., Joshi, Gomes et al. employ a chemical modulation approach of the cellular interactome to a hyperconnectivity state and show association with the increased response of pancreatic cancer cell lines to specific drugs, including those that target the MAPK-pathways and PI3K-mTOR pathway. To achieve this, the authors employ chemical modulation of the interactome via epichaperome inhibition with the small molecule PU-H71.

Published
2021

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