Publications by authors named "Maria Trissal"

14 Publications

  • Page 1 of 1

Cytokine Storm Unmasks Immunodeficiency in a Child With Severe COVID-19.

Clin Pediatr (Phila) 2021 05 6;60(4-5):205-209. Epub 2021 Mar 6.

Boston Children's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1177/0009922821999469DOI Listing
May 2021

Toddler With New Onset Diabetes and Atypical Hemolytic-Uremic Syndrome in the Setting of COVID-19.

Pediatrics 2021 02 9;147(2). Epub 2020 Oct 9.

Boston Children's Hospital, Boston, Massachusetts; and.

This is a novel case of a 16-month-old boy with a history of prematurity with intrauterine growth restriction, severe failure to thrive, microcephaly, pachygyria, agenesis of the corpus callosum, and postnatal embolic stroke, who presented with new-onset diabetes mellitus with diabetic ketoacidosis in the setting of severe acute respiratory syndrome coronavirus 2 infection, with a course complicated by atypical hemolytic syndrome (aHUS). This patient demonstrated remarkable insulin resistance in the period before aHUS diagnosis, which resolved with the first dose of eculizumab therapy. There is increasing evidence that COVID-19 is associated with thrombotic disorders and that microangiopathic processes and complement-mediated inflammation may be implicated. In this case report, we describe a pediatric patient with COVID-19 and a new complement-mediated microangiopathic thrombotic disease. Because whole-exome sequencing and extensive workup returned without a clear etiology for aHUS, this is likely a COVID-19 triggered case of aHUS versus an idiopathic case that was unmasked by the infection.
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http://dx.doi.org/10.1542/peds.2020-016774DOI Listing
February 2021

Single-Cell RNA-Seq Reveals Cellular Hierarchies and Impaired Developmental Trajectories in Pediatric Ependymoma.

Cancer Cell 2020 07;38(1):44-59.e9

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Ependymoma is a heterogeneous entity of central nervous system tumors with well-established molecular groups. Here, we apply single-cell RNA sequencing to analyze ependymomas across molecular groups and anatomic locations to investigate their intratumoral heterogeneity and developmental origins. Ependymomas are composed of a cellular hierarchy initiating from undifferentiated populations, which undergo impaired differentiation toward three lineages of neuronal-glial fate specification. While prognostically favorable groups of ependymoma predominantly harbor differentiated cells, aggressive groups are enriched for undifferentiated cell populations. The delineated transcriptomic signatures correlate with patient survival and define molecular dependencies for targeted treatment approaches. Taken together, our analyses reveal a developmental hierarchy underlying ependymomas relevant to biological and clinical behavior.
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http://dx.doi.org/10.1016/j.ccell.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479515PMC
July 2020

COVID-19 presenting with autoimmune hemolytic anemia in the setting of underlying immune dysregulation.

Pediatr Blood Cancer 2020 09 3;67(9):e28382. Epub 2020 Jun 3.

Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1002/pbc.28382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674227PMC
September 2020

MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells.

Immunity 2019 09 8;51(3):479-490.e6. Epub 2019 Aug 8.

Department of Medicine, Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address:

Natural killer (NK) cells are cytotoxic type 1 innate lymphoid cells (ILCs) that defend against viruses and mediate anti-tumor responses, yet mechanisms controlling their development and function remain incompletely understood. We hypothesized that the abundantly expressed microRNA-142 (miR-142) is a critical regulator of type 1 ILC biology. Interleukin-15 (IL-15) signaling induced miR-142 expression, whereas global and ILC-specific miR-142-deficient mice exhibited a cell-intrinsic loss of NK cells. Death of NK cells resulted from diminished IL-15 receptor signaling within miR-142-deficient mice, likely via reduced suppressor of cytokine signaling-1 (Socs1) regulation by miR-142-5p. ILCs persisting in Mir142 mice demonstrated increased expression of the miR-142-3p target αV integrin, which supported their survival. Global miR-142-deficient mice exhibited an expansion of ILC1-like cells concurrent with increased transforming growth factor-β (TGF-β) signaling. Further, miR-142-deficient mice had reduced NK-cell-dependent function and increased susceptibility to murine cytomegalovirus (MCMV) infection. Thus, miR-142 critically integrates environmental cues for proper type 1 ILC homeostasis and defense against viral infection.
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http://dx.doi.org/10.1016/j.immuni.2019.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750984PMC
September 2019

Loss-of-Function Mutations Derepress ASH1L to Increase Gene Expression and Promote Leukemogenesis.

Cancer Res 2018 07 3;78(13):3510-3521. Epub 2018 May 3.

Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.

Point mutations in the seed sequence of miR-142-3p are present in a subset of acute myelogenous leukemia (AML) and in several subtypes of B-cell lymphoma. Here, we show that mutations associated with AML result both in loss of miR-142-3p function and in decreased miR-142-5p expression. loss altered the hematopoietic differentiation of multipotent hematopoietic progenitors, enhancing their myeloid potential while suppressing their lymphoid potential. During hematopoietic maturation, loss of increased ASH1L protein expression and consequently resulted in the aberrant maintenance of gene expression in myeloid-committed hematopoietic progenitors. loss also enhanced the disease-initiating activity of -mutant hematopoietic cells in mice. Together these data suggest a novel model in which miR-142, through repression of ASH1L activity, plays a key role in suppressing expression during normal myeloid differentiation. AML-associated loss-of-function mutations of disrupt this negative signaling pathway, resulting in sustained expression in myeloid progenitors/myeloblasts and ultimately contributing to leukemic transformation. These findings provide mechanistic insights into the role of miRNAs in leukemogenesis and hematopoietic stem cell function. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-3592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030481PMC
July 2018

Expression profiling of snoRNAs in normal hematopoiesis and AML.

Blood Adv 2018 01;2(2):151-163

Division of Oncology.

Small nucleolar RNAs (snoRNAs) are noncoding RNAs that contribute to ribosome biogenesis and RNA splicing by modifying ribosomal RNA and spliceosome RNAs, respectively. We optimized a next-generation sequencing approach and a custom analysis pipeline to identify and quantify expression of snoRNAs in acute myeloid leukemia (AML) and normal hematopoietic cell populations. We show that snoRNAs are expressed in a lineage- and development-specific fashion during hematopoiesis. The most striking examples involve snoRNAs located in 2 imprinted loci, which are highly expressed in hematopoietic progenitors and downregulated during myeloid differentiation. Although most snoRNAs are expressed at similar levels in AML cells compared with CD34, a subset of snoRNAs showed consistent differential expression, with the great majority of these being decreased in the AML samples. Analysis of host gene expression, splicing patterns, and whole-genome sequence data for mutational events did not identify transcriptional patterns or genetic alterations that account for these expression differences. These data provide a comprehensive analysis of the snoRNA transcriptome in normal and leukemic cells and should be helpful in the design of studies to define the contribution of snoRNAs to normal and malignant hematopoiesis.
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http://dx.doi.org/10.1182/bloodadvances.2017006668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787869PMC
January 2018

Comprehensive discovery of noncoding RNAs in acute myeloid leukemia cell transcriptomes.

Exp Hematol 2017 11 28;55:19-33. Epub 2017 Jul 28.

The McDonnell Genome Institute, Washington University, St. Louis, MO; Department of Medicine, Washington University, St. Louis, MO; Siteman Cancer Center, Washington University, St. Louis, MO; Department of Biomedical Engineering, Washington University, St. Louis, MO. Electronic address:

To detect diverse and novel RNA species comprehensively, we compared deep small RNA and RNA sequencing (RNA-seq) methods applied to a primary acute myeloid leukemia (AML) sample. We were able to discover previously unannotated small RNAs using deep sequencing of a library method using broader insert size selection. We analyzed the long noncoding RNA (lncRNA) landscape in AML by comparing deep sequencing from multiple RNA-seq library construction methods for the sample that we studied and then integrating RNA-seq data from 179 AML cases. This identified lncRNAs that are completely novel, differentially expressed, and associated with specific AML subtypes. Our study revealed the complexity of the noncoding RNA transcriptome through a combined strategy of strand-specific small RNA and total RNA-seq. This dataset will serve as an invaluable resource for future RNA-based analyses.
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http://dx.doi.org/10.1016/j.exphem.2017.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5772960PMC
November 2017

MicroRNA-223 regulates granulopoiesis but is not required for HSC maintenance in mice.

PLoS One 2015 20;10(3):e0119304. Epub 2015 Mar 20.

Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America.

MIR233 is genetically or epigenetically silenced in a subset of acute myeloid leukemia (AML). MIR223 is normally expressed throughout myeloid differentiation and highly expressed in hematopoietic stem cells (HSCs). However, the contribution of MIR223 loss to leukemic transformation and HSC function is largely unknown. Herein, we characterize HSC function and myeloid differentiation in Mir223 deficient mice. We show that Mir223 loss results in a modest expansion of myeloid progenitors, but is not sufficient to induce a myeloproliferative disorder. Loss of Mir223 had no discernible effect on HSC quiescence, long-term repopulating activity, or self-renewal capacity. These results suggest that MIR223 loss is likely not an initiating event in AML but may cooperate with other AML associated oncogenes to induce leukemogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119304PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368818PMC
February 2016

Acquired copy number alterations of miRNA genes in acute myeloid leukemia are uncommon.

Blood 2013 Oct 5;122(15):e44-51. Epub 2013 Sep 5.

Jane Anne Nohl Division of Hematology, Department of Medicine, University of Southern California, Los Angeles, CA;

Altered microRNA (miRNA) expression is frequently observed in acute myelogenous leukemia (AML) and has been implicated in leukemic transformation. Whether somatic copy number alterations (CNAs) are a frequent cause of altered miRNA gene expression is largely unknown. Herein, we used comparative genomic hybridization with a custom high-resolution miRNA-centric array and/or whole-genome sequence data to identify somatic CNAs involving miRNA genes in 113 cases of AML, including 50 cases of de novo AML, 18 cases of relapsed AML, 15 cases of secondary AML following myelodysplastic syndrome, and 30 cases of therapy-related AML. We identified a total of 48 somatic miRNA gene-containing CNAs that were not identified by routine cytogenetics in 20 patients (18%). All these CNAs also included one or more protein coding genes. We identified a single case with a hemizygous deletion of MIR223, resulting in the complete loss of miR-223 expression. Three other cases of AML were identified with very low to absent miR-223 expression, an miRNA gene known to play a key role in myelopoiesis. However, in these cases, no somatic genetic alteration of MIR223 was identified, suggesting epigenetic silencing. These data show that somatic CNAs specifically targeting miRNA genes are uncommon in AML.
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http://dx.doi.org/10.1182/blood-2013-03-488007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795465PMC
October 2013

Complete characterization of the microRNAome in a patient with acute myeloid leukemia.

Blood 2010 Dec 28;116(24):5316-26. Epub 2010 Sep 28.

Deparment of Medicine, Washington University School of Medicine, St Louis, MO, USA.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and have been implicated in the pathogenesis of cancer. In this study, we applied next generation sequencing techniques to comprehensively assess miRNA expression, identify genetic variants of miRNA genes, and screen for alterations in miRNA binding sites in a patient with acute myeloid leukemia. RNA sequencing of leukemic myeloblasts or CD34(+) cells pooled from healthy donors showed that 472 miRNAs were expressed, including 7 novel miRNAs, some of which displayed differential expression. Sequencing of all known miRNA genes revealed several novel germline polymorphisms but no acquired mutations in the leukemia genome. Analysis of the sequence of the 3'-untranslated regions (UTRs) of all coding genes identified a single somatic mutation in the 3'-UTR of TNFAIP2, a known target of the PML-RARα oncogene. This mutation resulted in translational repression of a reporter gene in a Dicer-dependent fashion. This study represents the first complete characterization of the "miRNAome" in a primary human cancer and suggests that generation of miRNA binding sites in the UTR regions of genes is another potential mechanism by which somatic mutations can affect gene expression.
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http://dx.doi.org/10.1182/blood-2010-05-285395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012545PMC
December 2010

Identification of novel pancreatic adenocarcinoma cell-surface targets by gene expression profiling and tissue microarray.

Biochem Pharmacol 2010 Sep 25;80(5):748-54. Epub 2010 May 25.

H. Lee Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, United States.

Pancreatic cancer has a high mortality rate, which is generally related to the initial diagnosis coming at late stage disease combined with a lack of effective treatment options. Novel agents that selectively detect pancreatic cancer have potential for use in the molecular imaging of cancer, allowing for non-invasive determination of tumor therapeutic response and molecular characterization of the disease. Such agents may also be used for the targeted delivery of therapy to tumor cells while decreasing systemic effects. Using complementary assays of mRNA expression profiling to determine elevated expression in pancreatic cancer tissues relative to normal pancreas tissues, and validation of protein expression by immunohistochemistry on tissue microarray, we have identified cell-surface targets with potential for imaging and therapeutic agent development. Expression profiles of 2177 cell-surface genes for 28 pancreatic tumor specimens and 4 normal pancreas tissue samples were evaluated. Expression in normal tissues was evaluated using array data from 103 samples representing 28 organ sites as well as mining published data. One-hundred seventy unique targets were highly expressed in 2 or more of the pancreatic tumor specimens and were not expressed in the normal pancreas samples. Two targets (TLR2 and ABCC3) were further validated for protein expression by tissue microarray (TMA) based immunohistochemistry. These validated targets have potential for the development of diagnostic imaging and therapeutic agents for pancreatic cancer.
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http://dx.doi.org/10.1016/j.bcp.2010.05.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2914681PMC
September 2010

Solid-phase synthetic strategy and bioevaluation of a labeled delta-opioid receptor ligand Dmt-Tic-Lys for in vivo imaging.

Org Lett 2009 Jun;11(12):2479-82

Department of Chemistry, BIO5 Institute, The University of Arizona, Tucson, Arizona 85721, USA.

A general solid-phase synthetic strategy is developed to prepare fluorescent and/or lanthanide-labeled derivatives of the delta-opioid receptor (deltaOR) ligand H-Dmt-Tic-Lys(R)-OH. The high delta-OR affinity (K(i) = 3 nM) and desirable in vivo characteristics of the Cy5 derivative 1 suggest its usefulness for structure-function studies and receptor localization and as a high-contrast noninvasive molecular marker for live imaging ex vivo or in vivo.
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http://dx.doi.org/10.1021/ol900200kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756606PMC
June 2009

Gene expression profiling-based identification of cell-surface targets for developing multimeric ligands in pancreatic cancer.

Mol Cancer Ther 2008 Sep 2;7(9):3071-80. Epub 2008 Sep 2.

Translational Genomics Research Institute, 445 North Fifth Street, Phoenix, AZ 85004, USA.

Multimeric ligands are ligands that contain multiple binding domains that simultaneously target multiple cell-surface proteins. Due to cooperative binding, multimeric ligands can have high avidity for cells (tumor) expressing all targeting proteins and only show minimal binding to cells (normal tissues) expressing none or only some of the targets. Identifying combinations of targets that concurrently express in tumor cells but not in normal cells is a challenging task. Here, we describe a novel approach for identifying such combinations using genome-wide gene expression profiling followed by immunohistochemistry. We first generated a database of mRNA gene expression profiles for 28 pancreatic cancer specimens and 103 normal tissue samples representing 28 unique tissue/cell types using DNA microarrays. The expression data for genes that encode proteins with cell-surface epitopes were then extracted from the database and analyzed using a novel multivariate rule-based computational approach to identify gene combinations that are expressed at an efficient binding level in tumors but not in normal tissues. These combinations were further ranked according to the proportion of tumor samples that expressed the sets at efficient levels. Protein expression of the genes contained in the top ranked combinations was confirmed using immunohistochemistry on a pancreatic tumor tissue and normal tissue microarrays. Coexpression of targets was further validated by their combined expression in pancreatic cancer cell lines using immunocytochemistry. These validated gene combinations thus encompass a list of cell-surface targets that can be used to develop multimeric ligands for the imaging and treatment of pancreatic cancer.
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http://dx.doi.org/10.1158/1535-7163.MCT-08-0402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567866PMC
September 2008