A5039924892- Hematopoietic Stem Cell Transplantation
- Pluripotent Stem Cells Research
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Zebrafish Biomedical Research Applications
- Cancer Genomics and Diagnostics
- Hippo pathway signaling and YAP/TAZ
- FOXO transcription factor regulation
- Wnt/β-catenin signaling in development and cancer
- Acute Myeloid Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Systemic Lupus Erythematosus Research
- Immune responses and vaccinations
- Caveolin-1 and cellular processes
- Hematological disorders and diagnostics
- Mesenchymal stem cell research
- Erythrocyte Function and Pathophysiology
- MicroRNA in disease regulation
- Genetics and Physical Performance
- Acute Lymphoblastic Leukemia research
- Immune cells in cancer
- Genetics, Bioinformatics, and Biomedical Research
Icahn School of Medicine at Mount Sinai
2013-2020
Graduate School USA
2016-2020
Board of the Swiss Federal Institutes of Technology
2019
ETH Zurich
2019
The Graduate Center, CUNY
2016-2018
Stem Cell Institute
2016
Sanford Burnham Prebys Medical Discovery Institute
2012
Significance Li–Fraumeni syndrome is a rare disorder caused by germline TP53 mutations, predisposing patients to early-onset cancers, including osteosarcoma (OS). Here we demonstrate that strong expression of SFRP2, reported WNT antagonist, in OS patient samples correlates with poor survival and SFRP2 overexpression suppresses normal osteoblast differentiation, promotes features, facilitates angiogenesis via autocrine paracrine mechanisms an induced pluripotent stem cell disease model. We...
Hematopoietic stem cells (HSCs) exist in a dormant state and progressively lose regenerative potency as they undergo successive divisions. Why this functional decline occurs how information is encoded unclear. To better understand stored, we performed RNA sequencing on HSC populations differing only their divisional history. Comparative analysis revealed that genes upregulated with divisions are enriched for lineage regulated by cell-cycle-associated transcription factors, suggesting...
Transcription factor (TF)-based reprogramming of somatic tissues holds great promise for regenerative medicine. Previously, we demonstrated that the TFs GATA2, GFI1B, and FOS convert mouse human fibroblasts to hemogenic endothelial-like precursors generate hematopoietic stem progenitor (HSPC)-like cells over time. This conversion is lacking in robustness both yield biological function. Herein, show inclusion GFI1 cocktail significantly expands HSPC-like population. AFT024 coculture imparts...
Multiple cell types that share a common origin cooperate to form supportive niche for stem cells give rise blood and the of immune system.
Abstract Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigated an oncogenic role of secreted frizzled-related protein 2 (sFRP2) in P53 mutation-associated OS development. Interestingly, found that sFRP2 expression patient samples correlates survival. Systems-level analyses identified increases...
This protocol details the induction of a hemogenic program in mouse embryonic fibroblasts (MEFs) via overexpression transcription factors (TFs). We first designed reporter screen using MEFs from human CD34-tTA/TetO-H2BGFP (34/H2BGFP) double transgenic mice. CD34+ cells these mice label H2B histones with GFP, and cease labeling upon addition doxycycline (DOX). MEFS were transduced candidate TFs then observed for emergence GFP+ that would indicate acquisition hematopoietic or endothelial cell...
This protocol details the induction of a hemogenic program in mouse embryonic fibroblasts (MEFs) via overexpression transcription factors (TFs).We first designed reporter screen using MEFs from human CD34-tTA/TetO-H2BGFP (34/H2BGFP) double transgenic mice.CD34 + cells these mice label H2B histones with GFP, and cease labeling upon addition doxycycline (DOX).MEFS were transduced candidate TFs then observed for emergence GFP that would indicate acquisition hematopoietic or endothelial cell...
Abstract Osteosarcoma (OS), despite being a serious pediatric cancer with the lowest survival rate, is not well studied due to its rare occurrence. For this reason, studying OS in patient-specific manner more challenging. In an attempt establish method study manner, we previously generated Li-Fraumeni syndrome (LFS---a germline P53 mutation disease) patient specific iPSCs, and demonstrated that LFS-iPSC derived mesenchymal stem cells (MSCs) osteoblasts (OBs) can recapitulate tumorigenic...