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Article ; Online: Generation of three induced pluripotent stem cell lines from a patient with Kabuki syndrome carrying the KMT2D p.R4198X mutation.

Lager, Tyson W / Zuo, Junjun / Alam, Md Suhail / Calhoun, Barbara / Haldar, Kasturi / Panopoulos, Athanasia D

2022 Volume 62, Page(s) 102799

Abstract: Kabuki syndrome (KS) is a rare genetic disorder typically characterized by facial abnormalities, developmental delay, cognitive dysfunction, and organ impairment. In this report, fibroblast cells obtained from a KS patient containing a heterozygous KMT2D ...

Abstract	Kabuki syndrome (KS) is a rare genetic disorder typically characterized by facial abnormalities, developmental delay, cognitive dysfunction, and organ impairment. In this report, fibroblast cells obtained from a KS patient containing a heterozygous KMT2D c.12592 C>T mutation (p.R4198X) were reprogrammed using non-integrative Sendai virus to generate three induced pluripotent stem cell (iPSC) clones. The iPSC lines retained the KS patient mutation, and displayed normal karyotypes, pluripotency marker expression, and the ability to differentiate into the three germ layers.
MeSH term(s)	Abnormalities, Multiple ; Face/abnormalities ; Hematologic Diseases/genetics ; Humans ; Induced Pluripotent Stem Cells ; Mutation/genetics ; Vestibular Diseases/genetics
Language	English
Publishing date	2022-05-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2022.102799
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Article ; Online: A nanotherapeutic approach to selectively eliminate metastatic breast cancer cells by targeting cell surface GRP78.

Shin, Jaeho / Kim, Baksun / Lager, Tyson W / Mejia, Franklin / Guldner, Ian / Conner, Clay / Zhang, Siyuan / Panopoulos, Athanasia D / Bilgicer, Basar

Nanoscale

2023 Volume 15, Issue 32, Page(s) 13322–13334

Abstract: Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer ... ...

Abstract	Here, rational engineering of doxorubicin prodrug loaded peptide-targeted liposomal nanoparticles to selectively target metastatic breast cancer cells
MeSH term(s)	Animals ; Mice ; Endoplasmic Reticulum Chaperone BiP ; Membrane Proteins ; Cell Line, Tumor ; Prodrugs ; Glucose ; Peptides ; Doxorubicin/pharmacology ; Neoplasms
Chemical Substances	Endoplasmic Reticulum Chaperone BiP ; Membrane Proteins ; Prodrugs ; Glucose (IY9XDZ35W2) ; Peptides ; Doxorubicin (80168379AG)
Language	English
Publishing date	2023-08-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2515664-0
ISSN	2040-3372 ; 2040-3364
ISSN (online)	2040-3372
ISSN	2040-3364
DOI	10.1039/d3nr00800b
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Article: Multi-omic QTL mapping in early developmental tissues reveals phenotypic and temporal complexity of regulatory variants underlying GWAS loci.

Arthur, Timothy D / Nguyen, Jennifer P / D'Antonio-Chronowska, Agnieszka / Jaureguy, Jeffrey / Silva, Nayara / Henson, Benjamin / Panopoulos, Athanasia D / Belmonte, Juan Carlos Izpisua / D'Antonio, Matteo / McVicker, Graham / Frazer, Kelly A

bioRxiv : the preprint server for biology

2024

Abstract: Most GWAS loci are presumed to affect gene regulation, however, only ∼43% colocalize with expression quantitative trait loci (eQTLs). To address this colocalization gap, we identify eQTLs, chromatin accessibility QTLs (caQTLs), and histone acetylation ... ...

Abstract	Most GWAS loci are presumed to affect gene regulation, however, only ∼43% colocalize with expression quantitative trait loci (eQTLs). To address this colocalization gap, we identify eQTLs, chromatin accessibility QTLs (caQTLs), and histone acetylation QTLs (haQTLs) using molecular samples from three early developmental (EDev) tissues. Through colocalization, we annotate 586 GWAS loci for 17 traits by QTL complexity, QTL phenotype, and QTL temporal specificity. We show that GWAS loci are highly enriched for colocalization with complex QTL modules that affect multiple elements (genes and/or peaks). We also demonstrate that caQTLs and haQTLs capture regulatory variations not associated with eQTLs and explain ∼49% of the functionally annotated GWAS loci. Additionally, we show that EDev-unique QTLs are strongly depleted for colocalizing with GWAS loci. By conducting one of the largest multi-omic QTL studies to date, we demonstrate that many GWAS loci exhibit phenotypic complexity and therefore, are missed by traditional eQTL analyses.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.10.588874
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Article ; Online: Cell surface GRP78 and Dermcidin cooperate to regulate breast cancer cell migration through Wnt signaling.

Lager, Tyson W / Conner, Clay / Keating, Claudia R / Warshaw, Jane N / Panopoulos, Athanasia D

Oncogene

2021 Volume 40, Issue 23, Page(s) 4050–4059

Abstract: The heat shock protein GRP78 typically resides in the endoplasmic reticulum in normal tissues, but it has been shown to be expressed on the cell surface of several cancer cells, and some stem cells, where it can act as a signaling molecule by not-yet- ... ...

Abstract	The heat shock protein GRP78 typically resides in the endoplasmic reticulum in normal tissues, but it has been shown to be expressed on the cell surface of several cancer cells, and some stem cells, where it can act as a signaling molecule by not-yet-fully defined mechanisms. Although cell surface GRP78 (sGRP78) has emerged as an attractive chemotherapeutic target, understanding how sGRP78 is functioning in cancer has been complicated by the fact that sGRP78 can function in a cell-context dependent manner, with a diverse array of reported binding partners, to regulate a variety of cellular responses. We had previously shown that sGRP78 was important in regulating pluripotent stem cell (PSC) functions, and hypothesized that embryonic-like mechanisms of GRP78 were critical to regulating aggressive breast cancer cell functions. Here, using proteomics we identify Dermcidin (DCD) as a novel sGRP78 binding partner common to both PSCs and breast cancer cells. We show that GRP78 and DCD cooperate to regulate stem cell and cancer cell migration that is dependent on the cell surface functions of these proteins. Finally, we identify Wnt/β-catenin signaling, a critical pathway in stem cell and cancer cell biology, as an important downstream intermediate in regulating this migration phenotype.
MeSH term(s)	Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cell Movement/physiology ; Cell Proliferation/physiology ; Endoplasmic Reticulum Chaperone BiP/metabolism ; Female ; Humans ; Peptides/metabolism ; Stem Cells/metabolism ; Wnt Signaling Pathway
Chemical Substances	Endoplasmic Reticulum Chaperone BiP ; HSPA5 protein, human ; Peptides ; dermcidin
Language	English
Publishing date	2021-05-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-021-01821-6
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Article ; Online: An iPSC line derived from a human acute myeloid leukemia cell line (HL-60-iPSC) retains leukemic abnormalities and displays myeloid differentiation defects.

Yamasaki, Amanda E / Warshaw, Jane N / Kyalwazi, Beverly L / Matsui, Hiroko / Jepsen, Kristen / Panopoulos, Athanasia D

Stem cell research

2020 Volume 49, Page(s) 102096

Abstract: Cancer-derived iPSCs have provided valuable insight into oncogenesis, but human cancer cells can often be difficult to reprogram, especially in cases of complex genetic abnormalities. Here we report, to our knowledge, the first successful generation of ... ...

Abstract	Cancer-derived iPSCs have provided valuable insight into oncogenesis, but human cancer cells can often be difficult to reprogram, especially in cases of complex genetic abnormalities. Here we report, to our knowledge, the first successful generation of an iPSC line from a human immortalized acute myeloid leukemia (AML) cell line, the cell line HL-60. This iPSC line retains a majority of the leukemic genotype and displays defects in myeloid differentiation, thus providing a tool for modeling and studying AML.
MeSH term(s)	Cell Differentiation ; HL-60 Cells ; Hematopoiesis ; Humans ; Induced Pluripotent Stem Cells ; Leukemia, Myeloid, Acute/genetics
Language	English
Publishing date	2020-11-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2020.102096
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Article ; Online: Understanding the genetics behind complex human disease with large-scale iPSC collections.

Yamasaki, Amanda E / Panopoulos, Athanasia D / Belmonte, Juan Carlos Izpisua

Genome biology

2017 Volume 18, Issue 1, Page(s) 135

Abstract: Three recent studies analyzing large-scale collections of human induced pluripotent stem cell lines provide valuable insight into how genetic regulatory variation affects cellular and molecular traits. ...

Abstract	Three recent studies analyzing large-scale collections of human induced pluripotent stem cell lines provide valuable insight into how genetic regulatory variation affects cellular and molecular traits.
MeSH term(s)	Cell Differentiation ; Disease ; Genetic Variation ; Humans ; Induced Pluripotent Stem Cells ; Models, Genetic
Language	English
Publishing date	2017-07-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/s13059-017-1276-1
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Article ; Online: Two iPSC lines generated from the bone marrow of a relapsed/refractory AML patient display normal karyotypes and myeloid differentiation potential.

Yamasaki, Amanda E / King, Nicholas E / Matsui, Hiroko / Jepsen, Kristen / Panopoulos, Athanasia D

Stem cell research

2019 Volume 41, Page(s) 101587

Abstract: Using iPSCs to study cancer has been complicated by the fact that many cancer cells are difficult to reprogram, which has been attributed to the genomic abnormalities present. Acute Myeloid Leukemia (AML) is a complex disease that presents with various ... ...

Abstract	Using iPSCs to study cancer has been complicated by the fact that many cancer cells are difficult to reprogram, which has been attributed to the genomic abnormalities present. Acute Myeloid Leukemia (AML) is a complex disease that presents with various types of genomic aberrations that affect prognosis. Here we reprogrammed CD34+ cells from an AML patient containing a rare der(7)t(7;13) translocation associated with poor prognosis, who had relapsed and was refractory to current treatments. The generated AML-iPSCs displayed normal karyotypes and myeloid differentiation potential. These findings have implications for modeling and treating AML disease.
MeSH term(s)	Aged ; Bone Marrow/pathology ; Cell Differentiation ; Drug Resistance, Neoplasm ; Humans ; Induced Pluripotent Stem Cells/pathology ; Karyotype ; Leukemia, Myeloid, Acute/pathology ; Male ; Myeloid Cells/pathology ; Neoplasm Recurrence, Local/pathology ; Tumor Cells, Cultured
Language	English
Publishing date	2019-10-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1876-7753
ISSN (online)	1876-7753
DOI	10.1016/j.scr.2019.101587
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Article: Understanding the genetics behind complex human disease with large-scale iPSC collections

Yamasaki, Amanda E / Belmonte, Juan Carlos Izpisua / Panopoulos, Athanasia D

Genome biology. 2017 Dec., v. 18, no. 1

2017

Abstract	Three recent studies analyzing large-scale collections of human induced pluripotent stem cell lines provide valuable insight into how genetic regulatory variation affects cellular and molecular traits.
Keywords	cell lines ; genetic variation ; human diseases ; stem cells
Language	English
Dates of publication	2017-12
Size	p. 135.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/s13059-017-1276-1
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Article ; Online: Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and 'emergency' hematopoiesis.

Panopoulos, Athanasia D / Watowich, Stephanie S

Cytokine

2008 Volume 42, Issue 3, Page(s) 277–288

Abstract: Neutrophils are phagocytes whose principal function is to maintain anti-bacterial immunity. Neutrophils ingest and kill invading bacteria, releasing cytotoxic, chemotactic and inflammatory mediators at sites of infection. This serves to control the ... ...

Abstract	Neutrophils are phagocytes whose principal function is to maintain anti-bacterial immunity. Neutrophils ingest and kill invading bacteria, releasing cytotoxic, chemotactic and inflammatory mediators at sites of infection. This serves to control the immediate host immune response and attract other cells, such as macrophages and dendritic cells, which are important for establishing long-term adaptive immunity. Neutrophils thus contribute to both the initiation and the maintenance of inflammation at sites of infection. Aberrant neutrophil activity is deleterious; suppressed responses can cause extreme susceptibility to infection while overactivation can lead to excessive inflammation and tissue damage. This review will focus on neutrophil regulation by granulocyte colony-stimulating factor (G-CSF), the principal cytokine controlling neutrophil development and function. The review will emphasize the molecular aspects of G-CSF-driven granulopoiesis in steady state (healthy) conditions and during demand-driven or 'emergency' conditions elicited by infection or clinical administration of G-CSF. Understanding the molecular control of granulopoiesis will aid in the development of new approaches designed to treat disorders of neutrophil production and function.
MeSH term(s)	Animals ; Bacterial Infections/complications ; Bacterial Infections/immunology ; Bacterial Infections/physiopathology ; Cell Proliferation ; Gene Expression Regulation ; Granulocyte Colony-Stimulating Factor/pharmacology ; Granulocyte Colony-Stimulating Factor/physiology ; Humans ; Interleukin-17/physiology ; Mice ; Myelopoiesis/physiology ; Neutropenia/etiology ; Neutropenia/immunology ; Neutropenia/physiopathology ; Neutrophil Activation/physiology ; Receptors, Granulocyte Colony-Stimulating Factor/physiology ; Signal Transduction
Chemical Substances	Interleukin-17 ; Receptors, Granulocyte Colony-Stimulating Factor ; Granulocyte Colony-Stimulating Factor (143011-72-7)
Language	English
Publishing date	2008-04-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1018055-2
ISSN	1096-0023 ; 1043-4666
ISSN (online)	1096-0023
ISSN	1043-4666
DOI	10.1016/j.cyto.2008.03.002
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Article ; Online: Induced pluripotent stem cells in clinical hematology: potentials, progress, and remaining obstacles.

Panopoulos, Athanasia D / Belmonte, Juan C I

Current opinion in hematology

2012 Volume 19, Issue 4, Page(s) 256–260

Abstract: Purpose of review: With the advent of reprogramming came the possibility of generating patient-specific clinical therapies. The purpose of this review is to discuss the recent key developments and remaining limitations in the stem cell and hematopoietic ...

Abstract	Purpose of review: With the advent of reprogramming came the possibility of generating patient-specific clinical therapies. The purpose of this review is to discuss the recent key developments and remaining limitations in the stem cell and hematopoietic fields toward the goal of translating induced pluripotent stem cell (iPSC) technologies into the hematology clinic. Recent findings: Recent progress in the hematopoietic and reprogramming fields has included identification of hematopoietic stem cells (HSCs) capable of long-term engraftment at the single-cell level, improvements in ex-vivo expansion of HSCs, transdifferentiation of somatic cells into hematopoietic progenitors, and the 'correction' of several disease-specific iPSCs using various gene-targeting strategies. Summary: In light of recent advances, it is the hope that the hurdle of obtaining fully functional HSCs in a laboratory setting will be overcome through either in-vitro differentiation of pluripotent stem cells, ex-vivo expansion of HSCs obtained in vivo, or transdifferentiation from other somatic sources. Equally important will be for the reprogramming field to better understand the causes and consequences of the recently reported genetic/epigenetic variations present in iPSCs, especially within the context of gene-targeted strategies for correcting disease. The progress in the reprogramming and hematopoietic fields provides a strong foundation for future work toward the possible treatment of numerous hematological disorders using iPSC technologies.
MeSH term(s)	Cell Culture Techniques/methods ; Cell Differentiation ; Hematology/methods ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/cytology ; Humans ; Induced Pluripotent Stem Cells/cytology
Language	English
Publishing date	2012-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1153887-9
ISSN	1531-7048 ; 1065-6251
ISSN (online)	1531-7048
ISSN	1065-6251
DOI	10.1097/MOH.0b013e328353c78f
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