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Article ; Online: RNA-sequencing of Human Kidney Allografts and Delineation of T-Cell Genes, Gene Sets, and Pathways Associated With Acute T Cell-mediated Rejection.

Mueller, Franco B / Yang, Hua / Li, Carol / Dadhania, Darshana M / Xiang, Jenny Z / Salvatore, Steven P / Seshan, Surya V / Sharma, Vijay K / Suthanthiran, Manikkam / Muthukumar, Thangamani

Transplantation

2024 Volume 108, Issue 4, Page(s) 911–922

Abstract: Background: Delineation of T-cell genes, gene sets, pathways, and T-cell subtypes associated with acute T cell-mediated rejection (TCMR) may improve its management.: Methods: We performed bulk RNA-sequencing of 34 kidney allograft biopsies (16 Banff ... ...

Abstract	Background: Delineation of T-cell genes, gene sets, pathways, and T-cell subtypes associated with acute T cell-mediated rejection (TCMR) may improve its management. Methods: We performed bulk RNA-sequencing of 34 kidney allograft biopsies (16 Banff TCMR and 18 no rejection [NR] biopsies) from 34 adult recipients of human kidneys. Computational analysis was performed to determine the differential intragraft expression of T-cell genes at the level of single-gene, gene set, and pathways. Results: T-cell signaling pathway gene sets for plenary T-cell activation were overrepresented in TCMR biopsies compared with NR biopsies. Heightened expression of T-cell signaling genes was validated using external TCMR biopsies. Pro- and anti-inflammatory immune gene sets were enriched, and metabolism gene sets were depleted in TCMR biopsies compared with NR biopsies. Gene signatures of regulatory T cells, Th1 cells, Th2 cells, Th17 cells, T follicular helper cells, CD4 tissue-resident memory T cells, and CD8 tissue-resident memory T cells were enriched in TCMR biopsies compared with NR biopsies. T-cell exhaustion and anergy were also molecular attributes of TCMR. Gene sets associated with antigen processing and presentation, and leukocyte transendothelial migration were overexpressed in TCMR biopsies compared with NR biopsies. Cellular deconvolution of graft infiltrating cells by gene expression patterns identified CD8 T cell to be the most abundant T-cell subtype infiltrating the allograft during TCMR. Conclusions: Our delineation of intragraft T-cell gene expression patterns, in addition to yielding new biological insights, may help prioritize T-cell genes and T-cell subtypes for therapeutic targeting.
MeSH term(s)	Adult ; Humans ; Kidney Transplantation/adverse effects ; Kidney/pathology ; Transplantation, Homologous ; Allografts/pathology ; RNA ; Graft Rejection ; Biopsy
Chemical Substances	RNA (63231-63-0)
Language	English
Publishing date	2024-03-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004896
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Article: Selective modulation of gene expression in activated normal human peripheral blood mononuclear cells by store-operated calcium entry blocker BTP2.

Shankaranarayanan, Divya / Mantri, Madhav / Lagman, Mila / Li, Carol / Sharma, Vijay K / Muthukumar, Thangamani / Xiang, Jenny Z / De Vlaminck, Iwijn / Machaca, Khaled / Suthanthiran, Manikkam

Research square

2023

Abstract: Calcium is a critical signaling molecule in many cell types including immune cells. The calcium-release activated calcium channels (CRAC) responsible for store-operated calcium entry (SOCE) in immune cells are gated by STIM family members functioning as ... ...

Abstract	Calcium is a critical signaling molecule in many cell types including immune cells. The calcium-release activated calcium channels (CRAC) responsible for store-operated calcium entry (SOCE) in immune cells are gated by STIM family members functioning as sensors of Ca
Language	English
Publishing date	2023-03-13
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2618144/v1
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Article: Bcl-xL is translocated to the nucleus via CtBP2 to epigenetically promote metastasis.

Zhang, Tiantian / Li, Sha / Tan, Yingcai Adrian / Na, Joseph HyungJoon / Chen, Zhengming / Damle, Priyadarshan / Chen, Xiang / Choi, Soyoung / Mishra, Bikash / Wang, Dunrui / Grossman, Steven R / Jiang, Xuejun / Li, Yi / Chen, Yao-Tseng / Xiang, Jenny Z / Du, Yi-Chieh Nancy

bioRxiv : the preprint server for biology

2023

Abstract: Besides its mitochondria-based anti-apoptotic role, Bcl-xL also travels to the nucleus to promote cancer metastasis by upregulating global histone H3 trimethyl Lys4 (H3K4me3) and TGFβ transcription. How Bcl-xL is translocated into the nucleus and how ... ...

Abstract	Besides its mitochondria-based anti-apoptotic role, Bcl-xL also travels to the nucleus to promote cancer metastasis by upregulating global histone H3 trimethyl Lys4 (H3K4me3) and TGFβ transcription. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates H3K4me3 modification are not understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus. Knockdown of CtBP2 by shRNA decreases the nuclear portion of Bcl-xL and reverses Bcl-xL-induced cell migration and metastasis in mouse models. Furthermore, knockout of CtBP2 suppresses Bcl-xL transcription. The binding between Bcl-xL and CtBP2 is required for their interaction with MLL1, a histone H3K4 methyltransferase. Pharmacologic inhibition of MLL1 enzymatic activity reverses Bcl-xL-induced H3K4me3 and TGFβ mRNA upregulation as well as cell invasion. Moreover, cleavage under targets and release using nuclease (CUT&RUN) coupled with next generation sequencing reveals that H3K4me3 modifications are particularly enriched in the promotor region of genes encoding TGFβ and its signaling pathway in the cancer cells overexpressing Bcl-xL. Altogether, the metastatic function of Bcl-xL is mediated by its interaction with CtBP2 and MLL1.
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.26.538373
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Article ; Online: miR-431 Promotes Metastasis of Pancreatic Neuroendocrine Tumors by Targeting DAB2 Interacting Protein, a Ras GTPase Activating Protein Tumor Suppressor.

Zhang, Tiantian / Choi, Soyoung / Zhang, Tuo / Chen, Zhengming / Chi, Yudan / Huang, Shixia / Xiang, Jenny Z / Du, Yi-Chieh Nancy

The American journal of pathology

2020 Volume 190, Issue 3, Page(s) 689–701

Abstract: The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and an unfavorable survival rate. A better understanding of the drivers of PNET tumorigenesis is urgently needed. Distinct miRNA ... ...

Abstract	The incidence of pancreatic neuroendocrine tumor (PNET) is increasing, and it presents with various clinical manifestations and an unfavorable survival rate. A better understanding of the drivers of PNET tumorigenesis is urgently needed. Distinct miRNA signatures have been identified for different stages of tumorigenesis in both human and mouse PNETs. The functions of these miRNAs are poorly understood. miR-431 is the most up-regulated miRNA in the metastatic signature. However, it is unknown whether miR-431 contributes to metastasis of PNETs. Herein, we show that miR-431 overexpression activates Ras/extracellular signal-regulated kinase (Erk) signaling and promotes epithelial-mesenchymal transition, migration/invasion in vitro, and metastasis in both xenograft and spontaneous mouse models of PNET. Treatment of PNET cells with Erk inhibitor or locked nucleic acids sequestering miR-431 inhibits invasion. Four target prediction modules and dual-luciferase reporter assays were used to identify potential mRNA targets of miR-431. A Ras GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discovered as an miR-431 target. Overexpression of DAB2IP's rat homolog, but not its mutant defective in Ras GTPase activating protein activity, reverses miR-431's effect on promoting invasion, Erk phosphorylation, and epithelial-mesenchymal transition of PNETs. Taken together, miR-431 silences DAB2IP to active Ras/Erk and promote metastasis of PNETs. miR-431 may be targeted to manage metastatic PNETs.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism ; Carcinogenesis ; Epithelial-Mesenchymal Transition ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; MAP Kinase Signaling System ; Male ; Mice ; MicroRNAs/genetics ; Neoplasm Metastasis ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/pathology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Rats ; ras GTPase-Activating Proteins/genetics ; ras GTPase-Activating Proteins/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; DAB2 protein, human ; Dab2 protein, mouse ; MIRN431 microRNA, human ; MIRN431 microRNA, mouse ; MicroRNAs ; ras GTPase-Activating Proteins
Language	English
Publishing date	2020-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2943-9
ISSN	1525-2191 ; 0002-9440
ISSN (online)	1525-2191
ISSN	0002-9440
DOI	10.1016/j.ajpath.2019.11.007
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Article ; Online: Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay.

Orlando, Francesco / Romanel, Alessandro / Trujillo, Blanca / Sigouros, Michael / Wetterskog, Daniel / Quaini, Orsetta / Leone, Gianmarco / Xiang, Jenny Z / Wingate, Anna / Tagawa, Scott / Jayaram, Anuradha / Linch, Mark / Jamal-Hanjani, Mariam / Swanton, Charles / Rubin, Mark A / Wyatt, Alexander W / Beltran, Himisha / Attard, Gerhardt / Demichelis, Francesca

NAR cancer

2022 Volume 4, Issue 2, Page(s) zcac016

Abstract: Sequencing of cell-free DNA (cfDNA) in cancer patients' plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA ... ...

Abstract	Sequencing of cell-free DNA (cfDNA) in cancer patients' plasma offers a minimally-invasive solution to detect tumor cell genomic alterations to aid real-time clinical decision-making. The reliability of copy number detection decreases at lower cfDNA tumor fractions, limiting utility at earlier stages of the disease. To test a novel strategy for detection of allelic imbalance, we developed a prostate cancer bespoke assay, PCF_SELECT, that includes an innovative sequencing panel covering ∼25 000 high minor allele frequency SNPs and tailored analytical solutions to enable allele-informed evaluation. First, we assessed it on plasma samples from 50 advanced prostate cancer patients. We then confirmed improved detection of genomic alterations in samples with <10% tumor fractions when compared against an independent assay. Finally, we applied PCF_SELECT to serial plasma samples intensively collected from three patients previously characterized as harboring alterations involving DNA repair genes and consequently offered PARP inhibition. We identified more extensive pan-genome allelic imbalance than previously recognized in prostate cancer. We confirmed high sensitivity detection of
Language	English
Publishing date	2022-05-27
Publishing country	England
Document type	Journal Article
ISSN	2632-8674
ISSN (online)	2632-8674
DOI	10.1093/narcan/zcac016
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Article ; Online: Low-dose carbon monoxide suppresses metastatic progression of disseminated cancer cells.

Zhang, Tiantian / Zhang, George / Chen, Xiang / Chen, Zhengming / Tan, Adrian Y / Lin, Anthony / Zhang, Cheryl / Torres, Lisa K / Bajrami, Sandi / Zhang, Tuo / Zhang, Guoan / Xiang, Jenny Z / Hissong, Erika M / Chen, Yao-Tseng / Li, Yi / Du, Yi-Chieh Nancy

Cancer letters

2022 Volume 546, Page(s) 215831

Abstract: Low-dose carbon monoxide (CO) is under investigation in clinical trials to treat non-cancerous diseases and has an excellent safety profile. Due to early detection and cancer awareness, an increasing number of cancer patients are diagnosed at early ... ...

Abstract	Low-dose carbon monoxide (CO) is under investigation in clinical trials to treat non-cancerous diseases and has an excellent safety profile. Due to early detection and cancer awareness, an increasing number of cancer patients are diagnosed at early stages, when potentially curative surgical resection can be done. However, many patients ultimately experience recurrence. Here, we evaluate the therapeutic effect of CO on metastatic cancer progression. We show that 250 ppm CO inhibits the migration of multiple types of cancer cell lines, including breast, pancreatic, colon, prostate, liver, and lung cancer and reduces the ability to adhere to fibronectin. We demonstrate that in mouse models, 250 ppm inhaled CO inhibits lung metastasis of breast cancer and liver metastasis of pancreatic cancer. Moreover, low-dose CO suppresses recurrence and increases survival after surgical removal of primary pancreatic cancer in mice. Mechanistically, low-dose CO blocks transcription of heme importers, leading to diminished intracellular heme levels and a heme-regulated enzyme, cytochrome P4501B1 (CYP1B1). Either supplementing heme or overexpressing CYP1B1 reverses the anti-migration effect of low-dose CO. Taken together, low-dose CO therapy inhibits cell migration, reduces adhesion to fibronectin, prevents disseminated cancer cells from expanding into gross metastases, and improves survival in pre-clinical mouse models of metastasis.
MeSH term(s)	Animals ; Carbon Monoxide ; Fibronectins ; Heme ; Heme Oxygenase-1 ; Lung Neoplasms ; Male ; Mice ; Pancreatic Neoplasms
Chemical Substances	Fibronectins ; Heme (42VZT0U6YR) ; Carbon Monoxide (7U1EE4V452) ; Heme Oxygenase-1 (EC 1.14.14.18)
Language	English
Publishing date	2022-07-19
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2022.215831
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Article: Vascular oxidative stress causes neutrophil arrest in brain capillaries, leading to decreased cerebral blood flow and contributing to memory impairment in a mouse model of Alzheimerâ€™s disease.

bioRxiv : the preprint server for biology

2023

Abstract: Introduction: In this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD.: Methods: We ... ...

Abstract	Introduction: In this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD. Methods: We inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We used Results: We found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways. Discussion: Oxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target.
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.15.528710
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Article ; Online: Functional comparison of exome capture-based methods for transcriptomic profiling of formalin-fixed paraffin-embedded tumors.

Shohdy, Kyrillus S / Bareja, Rohan / Sigouros, Michael / Wilkes, David C / Dorsaint, Princesca / Manohar, Jyothi / Bockelman, Daniel / Xiang, Jenny Z / Kim, Rob / Ohara, Kentaro / Eng, Kenneth / Mosquera, Juan Miguel / Elemento, Olivier / Sboner, Andrea / Alonso, Alicia / Faltas, Bishoy M

NPJ genomic medicine

2021 Volume 6, Issue 1, Page(s) 66

Abstract: The availability of fresh frozen (FF) tissue is a barrier for implementing RNA sequencing (RNA-seq) in the clinic. The majority of clinical samples are stored as formalin-fixed, paraffin-embedded (FFPE) tissues. Exome capture platforms have been ... ...

Abstract	The availability of fresh frozen (FF) tissue is a barrier for implementing RNA sequencing (RNA-seq) in the clinic. The majority of clinical samples are stored as formalin-fixed, paraffin-embedded (FFPE) tissues. Exome capture platforms have been developed for RNA-seq from FFPE samples. However, these methods have not been systematically compared. We performed transcriptomic analysis of 32 FFPE tumor samples from 11 patients using three exome capture-based methods: Agilent SureSelect V6, TWIST NGS Exome, and IDT XGen Exome Research Panel. We compared these methods to the TruSeq RNA-seq of fresh frozen (FF-TruSeq) tumor samples from the same patients. We assessed the recovery of clinically relevant biological features. The Spearman's correlation coefficients between the global expression profiles of the three capture-based methods from FFPE and matched FF-TruSeq were high (rho = 0.72-0.9, p < 0.05). A significant correlation between the expression of key immune genes between individual capture-based methods and FF-TruSeq (rho = 0.76-0.88, p < 0.05) was observed. All exome capture-based methods reliably detected outlier expression of actionable gene transcripts, including ERBB2, MET, NTRK1, and PPARG. In urothelial cancer samples, the Agilent assay was associated with the highest molecular subtype concordance with FF-TruSeq (Cohen's k = 0.7, p < 0.01). The Agilent and IDT assays detected all the clinically relevant fusions that were initially identified in FF-TruSeq. All FFPE exome capture-based methods had comparable performance and concordance with FF-TruSeq. Our findings will enable the implementation of RNA-seq in the clinic to guide precision oncology approaches.
Language	English
Publishing date	2021-08-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2813848-X
ISSN	2056-7944 ; 2056-7944
ISSN (online)	2056-7944
ISSN	2056-7944
DOI	10.1038/s41525-021-00231-7
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Article ; Online: Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege.

Ma, Yinghua / Sannino, David / Linden, Jennifer R / Haigh, Sylvia / Zhao, Baohua / Grigg, John B / Zumbo, Paul / Dündar, Friederike / Butler, Daniel / Profaci, Caterina P / Telesford, Kiel / Winokur, Paige N / Rumah, Kareem R / Gauthier, Susan A / Fischetti, Vincent A / McClane, Bruce A / Uzal, Francisco A / Zexter, Lily / Mazzucco, Michael /

Rudick, Richard / Danko, David / Balmuth, Evan / Nealon, Nancy / Perumal, Jai / Kaunzner, Ulrike / Brito, Ilana L / Chen, Zhengming / Xiang, Jenny Z / Betel, Doron / Daneman, Richard / Sonnenberg, Gregory F / Mason, Christopher E / Vartanian, Timothy

The Journal of clinical investigation

2023 Volume 133, Issue 9

Abstract: Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR ... ...

Abstract	Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin-producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.
MeSH term(s)	Animals ; Humans ; Clostridium perfringens/genetics ; Multiple Sclerosis/genetics ; Gastrointestinal Microbiome ; Immune Privilege ; Lymphocytes ; Encephalomyelitis, Autoimmune, Experimental
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI163239
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Article ; Online: Molecular Evolution of Classic Hodgkin Lymphoma Revealed Through Whole-Genome Sequencing of Hodgkin and Reed Sternberg Cells.

Maura, Francesco / Ziccheddu, Bachisio / Xiang, Jenny Z / Bhinder, Bhavneet / Rosiene, Joel / Abascal, Federico / Maclachlan, Kylee H / Eng, Kenneth Wha / Uppal, Manik / He, Feng / Zhang, Wei / Gao, Qi / Yellapantula, Venkata D / Trujillo-Alonso, Vicenta / Park, Sunita I / Oberley, Matthew J / Ruckdeschel, Elizabeth / Lim, Megan S / Wertheim, Gerald B /

Barth, Matthew J / Horton, Terzah M / Derkach, Andriy / Kovach, Alexandra E / Forlenza, Christopher J / Zhang, Yanming / Landgren, Ola / Moskowitz, Craig H / Cesarman, Ethel / Imielinski, Marcin / Elemento, Olivier / Roshal, Mikhail / Giulino-Roth, Lisa

Blood cancer discovery

2023 Volume 4, Issue 3, Page(s) 208–227

Abstract: The rarity of malignant Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) limits the ability to study the genomics of cHL. To circumvent this, our group has previously optimized fluorescence-activated cell sorting to purify HRS ... ...

Abstract	The rarity of malignant Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) limits the ability to study the genomics of cHL. To circumvent this, our group has previously optimized fluorescence-activated cell sorting to purify HRS cells. Using this approach, we now report the whole-genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology of pathogenic events leading to cHL. We identified alterations in driver genes not previously described in cHL, APOBEC mutational activity, and the presence of complex structural variants including chromothripsis. We found that high ploidy in cHL is often acquired through multiple, independent chromosomal gains events including whole-genome duplication. Evolutionary timing analyses revealed that structural variants enriched for RAG motifs, driver mutations in B2M, BCL7A, GNA13, and PTPN1, and the onset of AID-driven mutagenesis usually preceded large chromosomal gains. This study provides a temporal reconstruction of cHL pathogenesis. Significance: Previous studies in cHL were limited to coding sequences and therefore not able to comprehensively decipher the tumor complexity. Here, leveraging cHL whole-genome characterization, we identify driver events and reconstruct the tumor evolution, finding that structural variants, driver mutations, and AID mutagenesis precede chromosomal gains. This article is highlighted in the In This Issue feature, p. 171.
MeSH term(s)	Humans ; Reed-Sternberg Cells/pathology ; Hodgkin Disease/genetics ; Hodgkin Disease/pathology ; Flow Cytometry ; Evolution, Molecular
Language	English
Publishing date	2023-01-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3028898-8
ISSN	2643-3249 ; 2643-3230
ISSN (online)	2643-3249
ISSN	2643-3230
DOI	10.1158/2643-3230.BCD-22-0128
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