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Your search keyword '"Suhasini, P."' showing total 11 results
Start Over Author "Suhasini, P." Journal nature communications
11 results on '"Suhasini, P."'

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

Author

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

Published
2023
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2. Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution

Author

Fame, Ryann M., Kalugin, Peter N., Petrova, Boryana, Xu, Huixin, Soden, Paul A., Shipley, Frederick B., Dani, Neil, Grant, Bradford, Pragana, Aja, Head, Joshua P., Gupta, Suhasini, Shannon, Morgan L., Chifamba, Fortunate F., Hawks-Mayer, Hannah, Vernon, Amanda, Gao, Fan, Zhang, Yong, Holtzman, Michael J., Heiman, Myriam, Andermann, Mark L., Kanarek, Naama, Lipton, Jonathan O., and Lehtinen, Maria K.

Published
2023
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3. RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells

Author

Herrejon Chavez, Florisela, Luo, Hanzhi, Cifani, Paolo, Pine, Alli, Chu, Eren L., Joshi, Suhasini, Barin, Ersilia, Schurer, Alexandra, Chan, Mandy, Chang, Kathryn, Han, Grace Y. Q., Pierson, Aspen J., Xiao, Michael, Yang, Xuejing, Kuehm, Lindsey M., Hong, Yuning, Nguyen, Diu T. T., Chiosis, Gabriela, Kentsis, Alex, Leslie, Christina, Vu, Ly P., and Kharas, Michael G.

Published
2023
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4. Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution

Author

Ryann M. Fame, Peter N. Kalugin, Boryana Petrova, Huixin Xu, Paul A. Soden, Frederick B. Shipley, Neil Dani, Bradford Grant, Aja Pragana, Joshua P. Head, Suhasini Gupta, Morgan L. Shannon, Fortunate F. Chifamba, Hannah Hawks-Mayer, Amanda Vernon, Fan Gao, Yong Zhang, Michael J. Holtzman, Myriam Heiman, Mark L. Andermann, Naama Kanarek, Jonathan O. Lipton, and Maria K. Lehtinen

Subjects
Science
Abstract

Abstract Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake Ttr mNeonGreen mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.

Published
2023
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5. 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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6. RNA binding protein SYNCRIP maintains proteostasis and self-renewal of hematopoietic stem and progenitor cells

Author

Florisela Herrejon Chavez, Hanzhi Luo, Paolo Cifani, Alli Pine, Eren L. Chu, Suhasini Joshi, Ersilia Barin, Alexandra Schurer, Mandy Chan, Kathryn Chang, Grace Y. Q. Han, Aspen J. Pierson, Michael Xiao, Xuejing Yang, Lindsey M. Kuehm, Yuning Hong, Diu T. T. Nguyen, Gabriela Chiosis, Alex Kentsis, Christina Leslie, Ly P. Vu, and Michael G. Kharas

Subjects
Science
Abstract

Abstract Tissue homeostasis is maintained after stress by engaging and activating the hematopoietic stem and progenitor compartments in the blood. Hematopoietic stem cells (HSCs) are essential for long-term repopulation after secondary transplantation. Here, using a conditional knockout mouse model, we revealed that the RNA-binding protein SYNCRIP is required for maintenance of blood homeostasis especially after regenerative stress due to defects in HSCs and progenitors. Mechanistically, we find that SYNCRIP loss results in a failure to maintain proteome homeostasis that is essential for HSC maintenance. SYNCRIP depletion results in increased protein synthesis, a dysregulated epichaperome, an accumulation of misfolded proteins and induces endoplasmic reticulum stress. Additionally, we find that SYNCRIP is required for translation of CDC42 RHO-GTPase, and loss of SYNCRIP results in defects in polarity, asymmetric segregation, and dilution of unfolded proteins. Forced expression of CDC42 recovers polarity and in vitro replating activities of HSCs. Taken together, we uncovered a post-transcriptional regulatory program that safeguards HSC self-renewal capacity and blood homeostasis.

Published
2023
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7. 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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8. The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction

Author

Maria Carmen Inda, Suhasini Joshi, Tai Wang, Alexander Bolaender, Srinivasa Gandu, John Koren III, Alicia Yue Che, Tony Taldone, Pengrong Yan, Weilin Sun, Mohammad Uddin, Palak Panchal, Matthew Riolo, Smit Shah, Afsar Barlas, Ke Xu, Lon Yin L. Chan, Alexandra Gruzinova, Sarah Kishinevsky, Lorenz Studer, Valentina Fossati, Scott A. Noggle, Julie R. White, Elisa de Stanchina, Sonia Sequeira, Kyle H. Anthoney, John W. Steele, Katia Manova-Todorova, Sujata Patil, Mark P. Dunphy, NagaVaraKishore Pillarsetty, Ana C. Pereira, Hediye Erdjument-Bromage, Thomas A. Neubert, Anna Rodina, Stephen D. Ginsberg, Natalia De Marco Garcia, Wenjie Luo, and Gabriela Chiosis

Subjects
Science
Abstract

The biology of Alzheimer’s disease (AD) remains unknown. We propose AD is a protein connectivity-based dysfunction disorder whereby a switch of the chaperome into epichaperomes rewires proteome-wide connectivity, leading to brain circuitry malfunction that can be corrected by novel therapeutics.

Published
2020
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9. Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system

Author

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

Published
2021
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10. HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons

Author

Sarah Kishinevsky, Tai Wang, Anna Rodina, Sun Young Chung, Chao Xu, John Philip, Tony Taldone, Suhasini Joshi, Mary L. Alpaugh, Alexander Bolaender, Simon Gutbier, Davinder Sandhu, Faranak Fattahi, Bastian Zimmer, Smit K. Shah, Elizabeth Chang, Carmen Inda, John Koren, Nathalie G. Saurat, Marcel Leist, Steven S. Gross, Venkatraman E. Seshan, Christine Klein, Mark J. Tomishima, Hediye Erdjument-Bromage, Thomas A. Neubert, Ronald C. Henrickson, Gabriela Chiosis, and Lorenz Studer

Subjects
Science
Abstract

The early molecular events that ultimately lead to neuronal cell death in pathologies such as Parkinson’s disease are poorly understood. Here the authors use pluripotent stem-cell-derived human midbrain neurons and chemical biology tools to gain molecular level insight into the events induced by toxic and genetic stresses that mimic those occurring during neurodegeneration.

Published
2018
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11. The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction

Author

Inda, Maria Carmen, Joshi, Suhasini, Wang, Tai, Bolaender, Alexander, Gandu, Srinivasa, Koren III, John, Che, Alicia Yue, Taldone, Tony, Yan, Pengrong, Sun, Weilin, Uddin, Mohammad, Panchal, Palak, Riolo, Matthew, Shah, Smit, Barlas, Afsar, Xu, Ke, Chan, Lon Yin L., Gruzinova, Alexandra, Kishinevsky, Sarah, Studer, Lorenz, Fossati, Valentina, Noggle, Scott A., White, Julie R., de Stanchina, Elisa, Sequeira, Sonia, Anthoney, Kyle H., Steele, John W., Manova-Todorova, Katia, Patil, Sujata, Dunphy, Mark P., Pillarsetty, NagaVaraKishore, Pereira, Ana C., Erdjument-Bromage, Hediye, Neubert, Thomas A., Rodina, Anna, Ginsberg, Stephen D., De Marco Garcia, Natalia, Luo, Wenjie, and Chiosis, Gabriela

Published
2020
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