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Article ; Online: Transcriptional Regulation of the Hippo Pathway: Current Understanding and Insights from Single-Cell Technologies.

Paul, Sayantanee / Xie, Shiqi / Yao, Xiaosai / Dey, Anwesha

2022 Volume 11, Issue 14

Abstract: The Hippo pathway regulates tissue homeostasis in normal development and drives oncogenic processes. In this review, we extensively discuss how YAP/TAZ/TEAD cooperate with other master transcription factors and epigenetic cofactors to orchestrate a broad ...

Abstract	The Hippo pathway regulates tissue homeostasis in normal development and drives oncogenic processes. In this review, we extensively discuss how YAP/TAZ/TEAD cooperate with other master transcription factors and epigenetic cofactors to orchestrate a broad spectrum of transcriptional responses. Even though these responses are often context- and lineage-specific, we do not have a good understanding of how such precise and specific transcriptional control is achieved-whether they are driven by differences in TEAD paralogs, or recruitment of cofactors to tissue-specific enhancers. We believe that emerging single-cell technologies would enable a granular understanding of how the Hippo pathway influences cell fate and drives oncogenic processes, ultimately allowing us to design better pharmacological agents against TEADs and identify robust pharmacodynamics markers of Hippo pathway inhibition.
MeSH term(s)	Carcinogenesis ; Gene Expression Regulation ; Hippo Signaling Pathway/genetics ; Humans ; Protein Serine-Threonine Kinases/genetics ; Signal Transduction ; Single-Cell Analysis ; Transcription Factors/metabolism
Chemical Substances	Transcription Factors ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-07-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11142225
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Establishment of seed biopriming in salt stress mitigation of rice plants by mangrove derived Bacillus sp

Dutta, Bhramar / Datta, Arunava / Dey, Anwesha / Ghosh, Alak K. / Bandopadhyay, Rajib

Biocatalysis and Agricultural Biotechnology. 2023 Feb. 07, p.102626-

2023 , Page(s) 102626–

Abstract: Salinity stress is one of the growing challenges for agro-ecosystems. Present study aimed to explore the role of halotolerant bacteria in alleviation of salinity stressed rice plants. Bacillus sp. strain PnD was isolated from Indian Sundarban Mangrove ... ...

Abstract	Salinity stress is one of the growing challenges for agro-ecosystems. Present study aimed to explore the role of halotolerant bacteria in alleviation of salinity stressed rice plants. Bacillus sp. strain PnD was isolated from Indian Sundarban Mangrove Forest, conferred plant growth promoting (PGP) traits like indole 3-acetic acid (IAA) production, phosphate solubilization, siderophore production but had negative effect of 1-aminoacyclopropane 1-carboxylate (ACC) deaminase activity. Rice seeds (Oryza sativa L.) of Amal-Mana variety were subjected to salinity stress for 24 hours by being immersing in 1% NaCl. Another set of seeds were soaked in a broth cultured with Bacillus sp strain PnD, containing 1% NaCl in the media, denoted as bioprimed condition. The seeds that were soaked in distilled water had no salt stress and weren't primed, served as control. All the treatments were assigned randomly to the seeds and each treatment was replicated three times resulting in nine experimental units. Completely randomized design was adopted in this experiment. Overall results showed bioprimed seeds soaked in 1% NaCl for 24 hours had significantly increased germination percentage, seedling growth, photosynthetic pigments content etc. compared to control and non-primed salinity exposed plants. Scanning electron micrograph revealed root colonization of bacteria in bioprimed seedlings, tissue distortion was also noted during salt stress. The study revealed that Bacillus sp. strain PnD is a potential plant growth promoting bacterium (PGPB), and the seed biopriming technique efficiently mitigate inhibitory effects of salinity in rice plants.
Keywords	Bacillus (bacteria) ; Oryza sativa ; agricultural biotechnology ; agroecosystems ; bacteria ; biocatalysis ; germination ; indole acetic acid ; mangrove forests ; phosphates ; photosynthesis ; rice ; salinity ; salt stress ; salt tolerance ; seedling growth ; siderophores ; solubilization ; Bacillus sp. ; Biopriming ; PGPB
Language	English
Dates of publication	2023-0207
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	2642052-1
ISSN	1878-8181
ISSN	1878-8181
DOI	10.1016/j.bcab.2023.102626
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine.

Dey, Anwesha / Varelas, Xaralabos / Guan, Kun-Liang

Nature reviews. Drug discovery

2020 Volume 19, Issue 7, Page(s) 480–494

Abstract: The Hippo pathway is an evolutionarily conserved signalling pathway with key roles in organ development, epithelial homeostasis, tissue regeneration, wound healing and immune modulation. Many of these roles are mediated by the transcriptional effectors ... ...

Abstract	The Hippo pathway is an evolutionarily conserved signalling pathway with key roles in organ development, epithelial homeostasis, tissue regeneration, wound healing and immune modulation. Many of these roles are mediated by the transcriptional effectors YAP and TAZ, which direct gene expression via control of the TEAD family of transcription factors. Dysregulated Hippo pathway and YAP/TAZ-TEAD activity is associated with various diseases, most notably cancer, making this pathway an attractive target for therapeutic intervention. This Review highlights the key findings from studies of Hippo pathway signalling across biological processes and diseases, and discusses new strategies and therapeutic implications of targeting this pathway.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Animals ; DNA-Binding Proteins/genetics ; Fibrosis/genetics ; Fibrosis/pathology ; Fibrosis/therapy ; Gene Expression Regulation ; Humans ; Neoplasms/genetics ; Neoplasms/pathology ; Neoplasms/therapy ; Nuclear Proteins/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Regenerative Medicine/methods ; Signal Transduction ; Transcription Factors/genetics ; Wound Healing/physiology
Chemical Substances	Adaptor Proteins, Signal Transducing ; DNA-Binding Proteins ; Nuclear Proteins ; TEAD1 protein, human ; Transcription Factors ; YAP1 protein, human ; TAFAZZIN protein, human (EC 2.3.1.-) ; Hippo protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2020-06-17
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2062954-0
ISSN	1474-1784 ; 1474-1776
ISSN (online)	1474-1784
ISSN	1474-1776
DOI	10.1038/s41573-020-0070-z
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Article ; Online: Synthesis, Kinetics, Reaction Mechanism, and Bioactivity Assays of a Dimeric Palladium Complex.

Dey, Anwesha / Kumar, Ramesh / Dutta, Bhramar / Bandopadhyay, Rajib / Chakrabortty, Sankha / Khan, Moonis Ali / Jeon, Byong Hun / Ghosh, Alak Kumar

ACS omega

2023 Volume 8, Issue 48, Page(s) 45653–45667

Abstract: A dimer of Pd(II), [(bpy)Pd(μ-OH) ...

Abstract	A dimer of Pd(II), [(bpy)Pd(μ-OH)
Language	English
Publishing date	2023-11-20
Publishing country	United States
Document type	Journal Article
ISSN	2470-1343
ISSN (online)	2470-1343
DOI	10.1021/acsomega.3c05944
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Article: Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.

An, Le / De Bruyn, Tom / Pang, Jodie / Ubhayakar, Savita / Salphati, Laurent / Zhang, Xing / Liu, Liling / Li, Ruina / Chan, Bryan / Dey, Anwesha / Levy, Elizabeth S

Pharmaceuticals (Basel, Switzerland)

2024 Volume 17, Issue 2

Abstract: Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. ... ...

Abstract	Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.
Language	English
Publishing date	2024-01-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17020179
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Article: Bacteriospermia and Male Infertility: Role of Oxidative Stress.

Das, Sandipan / Roychoudhury, Shubhadeep / Dey, Anwesha / Jha, Niraj Kumar / Kumar, Dhruv / Roychoudhury, Shatabhisha / Slama, Petr / Kesari, Kavindra Kumar

Advances in experimental medicine and biology

2022 Volume 1358, Page(s) 141–163

Abstract: Male infertility is one of the major challenging and prevalent diseases having diverse etiologies of which bacteriospermia play a significant role. It has been estimated that approximately 15% of all infertility cases are due to infections caused by ... ...

Abstract	Male infertility is one of the major challenging and prevalent diseases having diverse etiologies of which bacteriospermia play a significant role. It has been estimated that approximately 15% of all infertility cases are due to infections caused by uropathogens and in most of the cases bacteria are involved in infection and inflammation leading to the development of bacteriospermia. In response to bacterial load, excess infiltration of leukocytes in the urogenital tract occurs and concomitantly generates oxidative stress (OS). Bacteria may induce infertility either by directly interacting with sperm or by generating reactive oxygen species (ROS) and impair sperm parameters such as motility, volume, capacitation, hyperactivation. They may also induce apoptosis leading to sperm death. Acute bacteriospermia is related with another clinical condition called leukocytospermia and both compromise male fertility potential by OS-mediated damage to sperm leading to male infertility. However, bacteriospermia as a clinical condition as well as the mechanism of action remains poorly understood, necessitating further research in order to understand the role of individual bacterial species and their impact in male infertility.
MeSH term(s)	Antioxidants/pharmacology ; Humans ; Infertility, Male/etiology ; Infertility, Male/metabolism ; Male ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Spermatozoa/physiology
Chemical Substances	Antioxidants ; Reactive Oxygen Species
Language	English
Publishing date	2022-05-31
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-89340-8_7
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Article ; Online: Hippo Pathway in Cancer: Aberrant Regulation and Therapeutic Opportunities.

Calses, Philamer C / Crawford, James J / Lill, Jennie R / Dey, Anwesha

Trends in cancer

2019 Volume 5, Issue 5, Page(s) 297–307

Abstract: The Hippo pathway remains a central focus in both basic and translational research and is a key modulator of developmental biology. Dysregulation of the pathway is associated with a plethora of human cancers and there are multiple efforts to target key ... ...

Abstract	The Hippo pathway remains a central focus in both basic and translational research and is a key modulator of developmental biology. Dysregulation of the pathway is associated with a plethora of human cancers and there are multiple efforts to target key components of the pathway for disease intervention. In this review, we briefly highlight the latest research advances around the core components of the Hippo pathway in cancer. More specifically, we discuss several genetic aberrations of these factors as mechanisms for the development of cancers, including genetic amplification, deletion, and gene fusions. Additionally, we highlight the role of the Hippo pathway in cancer therapy resistance and tumor immunogenicity. Last, we summarize the ongoing efforts to target the pathway in cancers.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Drug Discovery ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction/drug effects
Chemical Substances	Antineoplastic Agents ; Biomarkers ; Hippo protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2019-05-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2019.04.001
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The Hippo Pathway as a Driver of Select Human Cancers.

Kulkarni, Aishwarya / Chang, Matthew T / Vissers, Joseph H A / Dey, Anwesha / Harvey, Kieran F

Trends in cancer

2020 Volume 6, Issue 9, Page(s) 781–796

Abstract: The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Although Hippo has been linked to multiple aspects of cancer, its role in this disease is incompletely understood. Large-scale pan- ...

Abstract	The Hippo pathway regulates myriad biological processes in diverse species and is a key cancer signaling network in humans. Although Hippo has been linked to multiple aspects of cancer, its role in this disease is incompletely understood. Large-scale pan-cancer analyses of core Hippo pathway genes reveal that the pathway is mutated at a high frequency only in select human cancers, including malignant mesothelioma and meningioma. Hippo pathway deregulation is also enriched in squamous epithelial cancers. We discuss cancer-related functions of the Hippo pathway and potential explanations for the cancer-restricted mutation profile of core Hippo pathway genes. Greater understanding of Hippo pathway deregulation in cancers will be essential to guide the imminent use of Hippo-targeted therapies.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinogenesis/genetics ; Carcinogenesis/pathology ; Cell Competition/genetics ; Cell Differentiation/genetics ; Cell Proliferation/genetics ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Humans ; Molecular Targeted Therapy/methods ; Mutation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Precision Medicine/methods ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/antagonists & inhibitors ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/genetics ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism ; Tumor Suppressor Proteins/antagonists & inhibitors ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/antagonists & inhibitors ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	Antineoplastic Agents ; BAP1 protein, human ; Biomarkers, Tumor ; TRAF7 protein, human ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins ; Tumor Suppressor Proteins ; Hippo protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2020.04.004
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Article ; Online: BAP1 promotes osteoclast function by metabolic reprogramming.

Rohatgi, Nidhi / Zou, Wei / Li, Yongjia / Cho, Kevin / Collins, Patrick L / Tycksen, Eric / Pandey, Gaurav / DeSelm, Carl J / Patti, Gary J / Dey, Anwesha / Teitelbaum, Steven L

Nature communications

2023 Volume 14, Issue 1, Page(s) 5923

Abstract: Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional ... ...

Abstract	Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1
MeSH term(s)	Animals ; Female ; Humans ; Male ; Mice ; Bone Density ; Citric Acid Cycle ; Deubiquitinating Enzymes ; Osteoclasts ; Osteogenesis/genetics ; Tumor Suppressor Proteins/genetics ; Ubiquitin Thiolesterase/genetics
Chemical Substances	BAP1 protein, human ; Deubiquitinating Enzymes (EC 3.4.19.12) ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-41629-4
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Article: Safety Considerations in the Development of Hippo Pathway Inhibitors in Cancers.

Kakiuchi-Kiyota, Satoko / Schutten, Melissa M / Zhong, Yu / Crawford, James J / Dey, Anwesha

Frontiers in cell and developmental biology

2019 Volume 7, Page(s) 156

Abstract: The Hippo pathway is a critical regulator of cell and organ growth and has emerged as a target for therapeutic intervention in cancers. Its signaling is thought to play an important role in various physiological processes including homeostasis and tissue ...

Abstract	The Hippo pathway is a critical regulator of cell and organ growth and has emerged as a target for therapeutic intervention in cancers. Its signaling is thought to play an important role in various physiological processes including homeostasis and tissue regeneration. To date there has been limited information about potential pharmacology-related (on-target) safety liabilities of Hippo pathway inhibitors in the context of cancer indications. Herein, we review data from human genetic disorders and genetically engineered rodent models to gain insight into safety liabilities that may emerge from the inhibition of Hippo pathway. Germline systemic deletion of murine Hippo pathway effectors (Yap, Taz, and Teads) resulted in embryonic lethality or developmental phenotypes. Mouse models with tissue-specific deletion (or mutant overexpression) of the key effectors in Hippo pathways have indicated that, at least in some tissues, Hippo signaling may be dispensable for physiological homeostasis; and appears to be critical for regeneration upon tissue damage, indicating that patients with underlying comorbidities and/or insults caused by therapeutic agents and/or comedications may have a higher risk. Caution should be taken in interpreting phenotypes from tissue-specific transgenic animal models since some tissue-specific promoters are turned on during development. In addition, therapeutic agents may result in systemic effects not well-predicted by animal models with tissue-specific gene deletion. Therefore, the development of models that allows for systemic deletion of Yap and/or Taz in adult animals will be key in evaluating the potential safety liabilities of Hippo pathway modulation. In this review, we focus on potential challenges and strategies for targeting the Hippo pathway in cancers.
Language	English
Publishing date	2019-08-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2019.00156
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