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Article ; Online: Autophagy-dependent cell death - where, how and why a cell eats itself to death.

Bialik, Shani / Dasari, Santosh K / Kimchi, Adi

2018 Volume 131, Issue 18

Abstract: Autophagy as a means of cell killing was first advanced by Clark's phenotypic description of 'Type II autophagic cell death' in 1990. However, this phenomenon later came into question, because the presence of autophagosomes in dying cells does not ... ...

Abstract	Autophagy as a means of cell killing was first advanced by Clark's phenotypic description of 'Type II autophagic cell death' in 1990. However, this phenomenon later came into question, because the presence of autophagosomes in dying cells does not necessarily signify that autophagy is the cause of demise, but rather may reflect the efforts of the cell to prevent it. Resolution of this issue comes from a more careful definition of autophagy-dependent cell death (ADCD) as a regulated cell death that is shown experimentally to require different components of the autophagy machinery without involvement of alternative cell death pathways. Following these strict criteria, ADCD has been validated in both lower model organisms and mammalian cells, highlighting its importance for developmental and pathophysiological cell death. Recently, researchers have defined additional morphological criteria that characterize ADCD and begun to explore how the established, well-studied autophagy pathway is subverted from a survival to a death function. This Review explores validated models of ADCD and focuses on the current understanding of the mechanisms by which autophagy can kill a cell.
MeSH term(s)	Autophagy/physiology ; Cell Death/physiology ; Humans
Language	English
Publishing date	2018-09-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.215152
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Article ; Online: EphA2- and HDAC-Targeted Combination Therapy in Endometrial Cancer.

International journal of molecular sciences

2024 Volume 25, Issue 2

Abstract: Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical ...

Abstract	Endometrial cancer is the most frequent malignant tumor of the female reproductive tract but lacks effective therapy. EphA2, a receptor tyrosine kinase, is overexpressed by various cancers including endometrial cancer and is associated with poor clinical outcomes. In preclinical models, EphA2-targeted drugs had modest efficacy. To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate. We hypothesized that combination therapy with an EphA2 inhibitor and panobinostat leads to synergistic cell death. Indeed, we found that the combination enhanced DNA damage, increased apoptosis, and decreased clonogenic survival in Ishikawa and Hec1A endometrial cancer cells and significantly reduced tumor burden in mouse models of endometrial carcinoma. Upon RNA sequencing, the combination was associated with downregulation of cell survival pathways, including senescence, cyclins, and cell cycle regulators. The Axl-PI3K-Akt-mTOR pathway was also decreased by combination therapy. Together, our results highlight EphA2 and histone deacetylase as promising therapeutic targets for endometrial cancer.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Apoptosis ; Cell Line, Tumor ; Endometrial Neoplasms/drug therapy ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Histone Deacetylase Inhibitors/therapeutic use ; Panobinostat/pharmacology ; Panobinostat/therapeutic use ; Phosphatidylinositol 3-Kinases ; Molecular Targeted Therapy ; Receptor, EphA2/antagonists & inhibitors
Chemical Substances	Histone Deacetylase Inhibitors ; Panobinostat (9647FM7Y3Z) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; EPHA2 protein, human ; Receptor, EphA2 (EC 2.7.10.1)
Language	English
Publishing date	2024-01-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25021278
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Article ; Online: Combination of EphA2- and Wee1-Targeted Therapies in Endometrial Cancer.

Dasari, Santosh K / Joseph, Robiya / Umamaheswaran, Sujanitha / Mangala, Lingegowda S / Bayraktar, Emine / Rodriguez-Aguayo, Cristian / Wu, Yutuan / Nguyen, Nghi / Powell, Reid T / Sobieski, Mary / Liu, Yuan / Chowdhury, Mamur A / Amero, Paola / Stephan, Clifford / Lopez-Berestein, Gabriel / Westin, Shannon N / Sood, Anil K

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we ... ...

Abstract	EphA2 tyrosine kinase is upregulated in many cancers and correlated with poor survival of patients, including those with endometrial cancer. EphA2-targeted drugs have shown modest clinical benefit. To improve the therapeutic response to such drugs, we performed a high-throughput chemical screen to discover novel synergistic partners for EphA2-targeted therapeutics. Our screen identified the Wee1 kinase inhibitor, MK1775, as a synergistic partner to EphA2, and this finding was confirmed using both in vitro and in vivo experiments. We hypothesized that Wee1 inhibition would sensitize cells to EphA2-targeted therapy. Combination treatment decreased cell viability, induced apoptosis, and reduced clonogenic potential in endometrial cancer cell lines. In vivo Hec1A and Ishikawa-Luc orthotopic mouse models of endometrial cancer showed greater anti-tumor responses to combination treatment than to either monotherapy. RNASeq analysis highlighted reduced cell proliferation and defective DNA damage response pathways as potential mediators of the combination's effects. In conclusion, our preclinical findings indicate that Wee1 inhibition can enhance the response to EphA2-targeted therapeutics in endometrial cancer; this strategy thus warrants further development.
MeSH term(s)	Animals ; Female ; Humans ; Mice ; Antineoplastic Agents/therapeutic use ; Apoptosis ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Endometrial Neoplasms/drug therapy ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Receptor, EphA2/antagonists & inhibitors ; Molecular Targeted Therapy
Chemical Substances	Antineoplastic Agents ; Cell Cycle Proteins ; Protein Kinase Inhibitors ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Receptor, EphA2 (EC 2.7.10.1) ; WEE1 protein, human (EC 2.7.10.2)
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043915
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Article ; Online: Targeting CCR2

Wu, Yutuan / Jennings, Nicholas B / Sun, Yunjie / Dasari, Santosh K / Bayraktar, Emine / Corvigno, Sara / Stur, Elaine / Glassman, Deanna / Mangala, Lingegowda S / Lankenau Ahumada, Adrian / Westin, Shannon N / Sood, Anil K / Hu, Wei

Journal of cancer research and clinical oncology

2022 Volume 148, Issue 4, Page(s) 803–821

Abstract: Purpose: Tumor-associated macrophages (TAMs) are known to contribute to adaptive resistance to anti-vascular endothelial growth factor (VEGF) antibody (AVA) therapy in ovarian cancer. BET (bromodomain and extra-terminal domain) inhibitors (BETi) may ... ...

Abstract	Purpose: Tumor-associated macrophages (TAMs) are known to contribute to adaptive resistance to anti-vascular endothelial growth factor (VEGF) antibody (AVA) therapy in ovarian cancer. BET (bromodomain and extra-terminal domain) inhibitors (BETi) may have unique roles in targeting TAMs. Our objective was to examine the effects of BETi on TAMs, especially in the context of enhancing the efficacy of AVA therapy. Methods: We conducted a series of in vitro (MTT assay, apoptosis, flow cytometry, and RNA sequencing) and in vivo (xenograft ovarian cancer model) experiments to determine the biological effects of BETi combined with AVA in ovarian cancer. For statistical analysis, a two-tailed Student's t test (equal variance) or ANOVA was used for multiple groups' comparison, and p < 0.05 was considered significant. Results: BETi resulted in a dose-dependent decrease in cell viability and induced apoptosis (p < 0.01) in ovarian cancer cells (SKOV3ip1, OVCAR5, and OVCAR8). Treatment with BETi significantly increased apoptosis in THP-1 monocytes and macrophages (PMA-differentiated THP-1; p < 0.01). Furthermore, BETi selectively induced greater apoptosis in M2-like macrophages (PMA and IL-4, IL-13-differentiated THP-1) (31.3%-36.1%) than in M1-like macrophages (PMA and LPS-differentiated THP-1) (12.4%-18.5%) (p < 0.01). Flow cytometry revealed that the percentage of M1-like macrophages (CD68 Conclusions: Our findings indicate a previously unrecognized role for BETi in selectively targeting CCR2
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Carcinoma, Ovarian Epithelial/metabolism ; Cell Line, Tumor ; Humans ; Macrophages ; Mice ; Ovarian Neoplasms/pathology ; Receptors, CCR2/metabolism
Chemical Substances	Antineoplastic Agents ; CCR2 protein, human ; Ccr2 protein, mouse ; Receptors, CCR2
Language	English
Publishing date	2022-01-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-021-03885-z
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Article ; Online: Stress, inflammation, and eicosanoids: an emerging perspective.

Umamaheswaran, Sujanitha / Dasari, Santosh K / Yang, Peiying / Lutgendorf, Susan K / Sood, Anil K

Cancer metastasis reviews

2018 Volume 37, Issue 2-3, Page(s) 203–211

Abstract: Clinical and experimental studies support the notion that adrenergic stimulation and chronic stress affect inflammation, metabolism, and tumor growth. Eicosanoids are also known to heavily influence inflammation while regulating certain stress responses. ...

Abstract	Clinical and experimental studies support the notion that adrenergic stimulation and chronic stress affect inflammation, metabolism, and tumor growth. Eicosanoids are also known to heavily influence inflammation while regulating certain stress responses. However, additional work is needed to understand the full extent of interactions between the stress-related pathways and eicosanoids. Here, we review the potential influences that stress, inflammation, and metabolic pathways have on each other, in the context of eicosanoids. Understanding the intricacies of such interactions could provide insights on how systemic metabolic effects mediated by the stress pathways can be translated into therapies for cancer and other diseases.
MeSH term(s)	Animals ; Disease Susceptibility ; Eicosanoids/metabolism ; Humans ; Inflammation/complications ; Inflammation/etiology ; Inflammation/metabolism ; Lipid Metabolism ; Metabolic Networks and Pathways ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Stress, Physiological ; Stress, Psychological/complications ; Stress, Psychological/metabolism
Chemical Substances	Eicosanoids
Language	English
Publishing date	2018-06-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604857-2
ISSN	1573-7233 ; 0167-7659
ISSN (online)	1573-7233
ISSN	0167-7659
DOI	10.1007/s10555-018-9741-1
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Zs.A 1812: Show issues

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Article ; Online: Gain-of-function p53 protein transferred via small extracellular vesicles promotes conversion of fibroblasts to a cancer-associated phenotype.

Ma, Shaolin / McGuire, Michael H / Mangala, Lingegowda S / Lee, Sanghoon / Stur, Elaine / Hu, Wen / Bayraktar, Emine / Villar-Prados, Alejandro / Ivan, Cristina / Wu, Sherry Y / Yokoi, Akira / Dasari, Santosh K / Jennings, Nicholas B / Liu, Jinsong / Lopez-Berestein, Gabriel / Ram, Prahlad / Sood, Anil K

Cell reports

2021 Volume 34, Issue 6, Page(s) 108726

Abstract: Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs). Small EVs (≤200 nm) have been considered critical messengers of cellular communication ... ...

Abstract	Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs). Small EVs (≤200 nm) have been considered critical messengers of cellular communication during tumor development. Here, we demonstrate that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to fibroblasts. GOF p53 protein is selectively bound by heat shock protein 90 (HSP90), a chaperone protein, and packaged into small EVs. Inhibition of HSP90 activity blocks packaging of GOF, but not wild-type, p53 in small EVs. GOF p53-containing small EVs result in their conversion to cancer-associated fibroblasts. In vivo studies reveal that GOF p53-containing small EVs can enhance tumor growth and promote fibroblast transformation into a cancer-associated phenotype. These findings provide a better understanding of the complex interactions between cancer and stromal cells and may have therapeutic implications.
MeSH term(s)	Animals ; Cancer-Associated Fibroblasts/metabolism ; Colorectal Neoplasms/metabolism ; Extracellular Vesicles/genetics ; Extracellular Vesicles/metabolism ; Extracellular Vesicles/transplantation ; Female ; Gain of Function Mutation ; HT29 Cells ; Humans ; Mice ; Mice, Knockout ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2021-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.108726
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Article ; Online: Gene Body Methylation of the Lymphocyte-Specific Gene

McGuire, Michael H / Dasari, Santosh K / Yao, Hui / Wen, Yunfei / Mangala, Lingegowda S / Bayraktar, Emine / Ma, Wencai / Ivan, Cristina / Shoshan, Einav / Wu, Sherry Y / Jonasch, Eric / Bar-Eli, Menashe / Wang, Jing / Baggerly, Keith A / Sood, Anil K

Molecular cancer research : MCR

2021 Volume 19, Issue 11, Page(s) 1917–1928

Abstract: Investigations into the function of nonpromoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional ... ...

Abstract	Investigations into the function of nonpromoter DNA methylation have yielded new insights into epigenetic regulation of gene expression. Previous studies have highlighted the importance of distinguishing between DNA methylation in discrete functional regions; however, integrated nonpromoter DNA methylation and gene expression analyses across a wide number of tumor types and corresponding normal tissues have not been performed. Through integrated analysis of gene expression and DNA methylation profiles, we examined 32 tumor types and identified 57 tumor suppressors and oncogenes out of 260 genes exhibiting a correlation of > 0.5 between gene body methylation and gene expression in at least one tumor type. The lymphocyte-specific gene
MeSH term(s)	Animals ; CARD Signaling Adaptor Proteins/metabolism ; DNA Methylation/genetics ; Female ; Humans ; Lymphocytes/metabolism ; Mice ; Mice, Nude ; Prognosis ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; Transfection
Chemical Substances	CARD Signaling Adaptor Proteins ; Card11 protein, mouse ; mTOR protein, mouse (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2098788-2
ISSN	1557-3125 ; 1541-7786
ISSN (online)	1557-3125
ISSN	1541-7786
DOI	10.1158/1541-7786.MCR-20-0753
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Zs.A 5744: Show issues

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Article ; Online: Signalome-wide RNAi screen identifies GBA1 as a positive mediator of autophagic cell death.

Dasari, Santosh K / Bialik, Shani / Levin-Zaidman, Smadar / Levin-Salomon, Vered / Merrill, Alfred H / Futerman, Anthony H / Kimchi, Adi

Cell death and differentiation

2017 Volume 24, Issue 7, Page(s) 1288–1302

Abstract: Activating alternative cell death pathways, including autophagic cell death, is a promising direction to overcome the apoptosis resistance observed in various cancers. Yet, whether autophagy acts as a death mechanism by over consumption of intracellular ... ...

Abstract	Activating alternative cell death pathways, including autophagic cell death, is a promising direction to overcome the apoptosis resistance observed in various cancers. Yet, whether autophagy acts as a death mechanism by over consumption of intracellular components is still controversial and remains undefined at the ultrastructural and the mechanistic levels. Here we identified conditions under which resveratrol-treated A549 lung cancer cells die by a mechanism that fulfills the previous definition of autophagic cell death. The cells displayed a strong and sustained induction of autophagic flux, cell death was prevented by knocking down autophagic genes and death occurred in the absence of apoptotic or necroptotic pathway activation. Detailed ultrastructural characterization revealed additional critical events, including a continuous increase over time in the number of autophagic vacuoles, in particular autolysosomes, occupying most of the cytoplasm at terminal stages. This was followed by loss of organelles, disruption of intracellular membranes including the swelling of perinuclear space and, occasionally, a unique type of nuclear shedding. A signalome-wide shRNA-based viability screen was applied to identify positive mediators of this type of autophagic cell death. One top hit was GBA1, the Gaucher disease-associated gene, which encodes glucocerebrosidase, an enzyme that metabolizes glucosylceramide to ceramide and glucose. Interestingly, glucocerebrosidase expression levels and activity were elevated, concomitantly with increased intracellular ceramide levels, both of which correlated in time with the appearance of the unique death characteristics. Transfection with siGBA1 attenuated the increase in glucocerebrosidase activity and the intracellular ceramide levels. Most importantly, GBA1 knockdown prevented the strong increase in LC3 lipidation, and many of the ultrastructural changes characteristic of this type of autophagic cell death, including a significant decrease in cytoplasmic area occupied by autophagic vacuoles. Together, these findings highlight the critical role of GBA1 in mediating enhanced self-consumption of intracellular components and endomembranes, leading to autophagic cell death.
Language	English
Publishing date	2017-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1225672-9
ISSN	1476-5403 ; 1350-9047
ISSN (online)	1476-5403
ISSN	1350-9047
DOI	10.1038/cdd.2017.80
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Zs.A 4230: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Death by over-eating: The Gaucher disease associated gene GBA1, identified in a screen for mediators of autophagic cell death, is necessary for developmental cell death in Drosophila midgut.

Dasari, Santosh K / Schejter, Eyal / Bialik, Shani / Shkedy, Aya / Levin-Salomon, Vered / Levin-Zaidman, Smadar / Kimchi, Adi

Cell cycle (Georgetown, Tex.)

2017 Volume 16, Issue 21, Page(s) 2003–2010

Abstract: Autophagy is critical for homeostasis and cell survival during stress, but can also lead to cell death, a little understood process that has been shown to contribute to developmental cell death in lower model organisms, and to human cancer cell death. We ...

Abstract	Autophagy is critical for homeostasis and cell survival during stress, but can also lead to cell death, a little understood process that has been shown to contribute to developmental cell death in lower model organisms, and to human cancer cell death. We recently reported
MeSH term(s)	Animals ; Autophagy/physiology ; Drosophila/metabolism ; Gaucher Disease/metabolism ; Glucosylceramidase/metabolism ; Humans ; Lysosomes/metabolism ; Lysosomes/ultrastructure ; Parkinson Disease/genetics
Chemical Substances	Glucosylceramidase (EC 3.2.1.45)
Language	English
Publishing date	2017-10-09
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.1080/15384101.2017.1380134
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Article ; Online: Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L.

LaFargue, Christopher J / Amero, Paola / Noh, Kyunghee / Mangala, Lingegowda S / Wen, Yunfei / Bayraktar, Emine / Umamaheswaran, Sujanitha / Stur, Elaine / Dasari, Santosh K / Ivan, Cristina / Pradeep, Sunila / Yoo, Wonbeak / Lu, Chunhua / Jennings, Nicholas B / Vathipadiekal, Vinod / Hu, Wei / Chelariu-Raicu, Anca / Ku, Zhiqiang / Deng, Hui /

Xiong, Wei / Choi, Hyun-Jin / Hu, Min / Kiyama, Takae / Mao, Chai-An / Ali-Fehmi, Rouba / Birrer, Michael J / Liu, Jinsong / Zhang, Ningyan / Lopez-Berestein, Gabriel / de Franciscis, Vittorio / An, Zhiqiang / Sood, Anil K

Nature communications

2023 Volume 14, Issue 1, Page(s) 2407

Abstract: Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important ...

Abstract	Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility.
MeSH term(s)	Humans ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Bevacizumab/pharmacology ; Bevacizumab/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Neoplasms/drug therapy ; Neoplasms/genetics ; Angiogenesis Inhibitors/pharmacology ; Angiogenesis Inhibitors/therapeutic use ; Apoptosis Regulatory Proteins ; Receptors, Scavenger
Chemical Substances	Vascular Endothelial Growth Factor A ; Bevacizumab (2S9ZZM9Q9V) ; Antibodies, Monoclonal ; Angiogenesis Inhibitors ; CD5L protein, human ; Apoptosis Regulatory Proteins ; Receptors, Scavenger
Language	English
Publishing date	2023-04-26
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-36910-5
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