A5027603944- RNA modifications and cancer
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Tissue Engineering and Regenerative Medicine
- Hemoglobinopathies and Related Disorders
- Erythrocyte Function and Pathophysiology
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Neuroscience and Neural Engineering
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Pancreatic and Hepatic Oncology Research
- Immunodeficiency and Autoimmune Disorders
- Lysosomal Storage Disorders Research
- Acute Myeloid Leukemia Research
- Adipose Tissue and Metabolism
- Hematopoietic Stem Cell Transplantation
- Single-cell and spatial transcriptomics
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
ProterixBio (United States)
2023-2024
Boston Children's Hospital
2013-2023
Dana-Farber Cancer Institute
2015-2023
Harvard University
2011-2023
Broad Institute
2015-2023
Massachusetts Institute of Technology
2016-2022
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2016-2021
University of Verona
2012-2014
Albert Einstein College of Medicine
2011-2012
Brigham and Women's Hospital
2011-2012
Two opposite views of cardiac growth are currently held; one the heart as a static organ characterized by large number cardiomyocytes that present at birth and live long organism, other highly plastic in which myocyte compartment is restored several times during course life.The average age cardiomyocytes, vascular endothelial cells (ECs), fibroblasts their turnover rates were measured retrospective (14)C dating 19 normal hearts 2 to 78 years 17 explanted failing 22 70 age. We report human...
Age and coronary artery disease may negatively affect the function of human cardiac stem cells (hCSCs) their potential therapeutic efficacy for autologous cell transplantation in failing heart.
Two categories of cardiac stem cells (CSCs) with predominantly myogenic (mCSC) and vasculogenic (vCSC) properties have been characterized in the human heart. However, it is unknown whether functionally competent CSCs both classes are present myocardium patients affected by end-stage failure, these can be harvested from relatively small myocardial samples.To establish a clinically relevant number mCSCs vCSCs isolated expanded endomyocardial biopsies undergoing transplantation or left...
Significance Methods for identifying causal variants underlying human diseases have been greatly enhanced by whole-exome sequencing; however, this approach overlooks mutations that occur within noncoding regulatory regions. Moreover, the mechanisms how such result in disease are poorly understood. In study, we interrogated binding sites of blood cell transcription factor GATA1 elements mutated cases red disorders creating small-targeted deletions model lines. These cause a major reduction...
Abstract The molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge this process. Here, we studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence HSCs vivo. By generating faithful model primary coupling functional studies with integrative single-cell genomic analyses, uncover key transcriptional...
Understanding the mechanisms that regulate trafficking of human cardiac stem cells (hCSCs) may lead to development new therapeutic approaches for failing heart.We tested whether motility hCSCs in immunosuppressed infarcted animals is controlled by guidance system involves interaction Eph receptors with ephrin ligands.Within niches, cardiomyocytes expressed preferentially A1 ligand, whereas possessed EphA2 receptor. Treatment resulted rapid internalization A1-EphA2 complex, posttranslational...
The Wiskott Aldrich syndrome (WAS) is due to mutations of the WAS gene encoding for cytoskeletal protein (WASp), leading abnormal downstream signaling from T cell and B antigen receptors (TCR, BCR). We hypothesized that impaired through TCR BCR in would subsequently lead aberrations immune repertoire patients. Using next generation sequencing, receptor beta (TRB) immunoglobulin heavy chain (IGH) repertoires 8 patients with 6 controls were sequenced. Clonal expansions identified within memory...
Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically "cold" tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human MSS CRC is not clear. We used transcriptome profiling, in silico analysis, immunohistochemistry, western blot, RT-qPCR immunofluorescence staining to characterize novel biomarkers. effects of selective antagonists were tested vitro assays long term viability analysis kinase active forms...
Key mechanisms of fetal hemoglobin (HbF) regulation and switching have been elucidated through studies human genetic variation, including mutations in the HBG1/2 promoters, deletions β-globin locus, variation impacting BCL11A. While this has led to substantial insights, there not a unified understanding how these distinct genetically-nominated elements, as well other key transcription factors such ZBTB7A, collectively interact regulate HbF. A limitation inability model specific changes...