A5035050411- Hematopoietic Stem Cell Transplantation
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Growth Hormone and Insulin-like Growth Factors
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Childhood Cancer Survivors' Quality of Life
- Chronic Myeloid Leukemia Treatments
- Polyomavirus and related diseases
- Epigenetics and DNA Methylation
- Renal and related cancers
- Acute Myeloid Leukemia Research
- Cancer-related molecular mechanisms research
- Blood Coagulation and Thrombosis Mechanisms
- RNA Interference and Gene Delivery
- Lymphoma Diagnosis and Treatment
- Complement system in diseases
- Cancer Immunotherapy and Biomarkers
- FOXO transcription factor regulation
- Adipose Tissue and Metabolism
- Cytokine Signaling Pathways and Interactions
- Neutropenia and Cancer Infections
- Signaling Pathways in Disease
- Renal Transplantation Outcomes and Treatments
Atrium Medical Cente
2025
Levine Children's Hospital
2019-2024
Johns Hopkins University
2012-2021
Johns Hopkins Medicine
2012-2021
Sidney Kimmel Comprehensive Cancer Center
2012-2016
Johns Hopkins Hospital
2016
University of Maryland, Baltimore
2013
California Institute for Regenerative Medicine
2013
Stanford University
2013
University of Michigan
2000-2009
The rigorous characterization of distinct induced pluripotent stem cells (iPSC) derived from multiple reprogramming technologies, somatic sources, and donors is required to understand potential sources variability downstream potential. To achieve this goal, the Progenitor Cell Biology Consortium performed comprehensive experimental genomic analyses 58 iPSC ten laboratories generated using a variety genes, vectors, cells. Associated global molecular studies identified functionally informative...
Abstract Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication of hematopoietic stem cell transplantation (HSCT). A single-center prospective screening study has shown that the incidence TA-TMA much higher than prior retrospective studies did not systematically screen. These data have been replicated in multicenter study. Our objective was to determine and risk factors for compare outcomes pediatric HSCT patients with without TA-TMA. Patients were prospectively...
The generation of vascular progenitors (VPs) from human induced pluripotent stem cells (hiPSCs) has great potential for treating disorders such as ischemic retinopathies. However, long-term in vivo engraftment hiPSC-derived VPs into the retina not yet been reported. This goal may be limited by low differentiation yield, greater senescence, and poor proliferation cells. To evaluate hiPSCs retinopathies, we generated a repertoire viral-integrated nonintegrated fibroblast cord blood...
The derivation and maintenance of human pluripotent stem cells (hPSCs) in stable naïve states has a wide impact developmental biology. However, hPSCs are unstable classical mouse embryonic cell (ESC) WNT MEK/ERK signal inhibition (2i) culture. We show that broad repertoire conventional hESC transgene-independent induced (hiPSC) lines could be reverted to preimplantation inner mass (ICM)-like with only WNT, MEK/ERK, tankyrase (LIF-3i). LIF-3i-reverted retained normal karyotypes genomic...
Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There great success using HLA-matched related donors these patients; however, the use of alternative has been associated with increased graft failure, graft-versus-host disease (GVHD), transplant-related mortality (TRM). HSCT post-transplantation cyclophosphamide (PT/Cy) GVHD prophylaxis performed...
Lower-intensity conditioning regimens for haploidentical blood or marrow transplantation (BMT) are safe and efficacious adult patients with hematologic malignancies. We report data pediatric/young high-risk malignancies (n = 40) treated nonmyeloablative BMT post-transplantation cyclophosphamide from 2003 to 2015. Patients received a preparative regimen of fludarabine, cyclophosphamide, total body irradiation. Post-transplantation immunosuppression consisted mycophenolate mofetil, tacrolimus....
Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) posttransplant cyclophosphamide (PTCy). To our knowledge, we report from the first multicenter trial pediatric and young acute leukemias myelodysplastic syndrome (MDS) in Pediatric Transplantation Cellular Therapy Consortium. Nine centers performed transplants 32 having or MDS, myeloablative conditioning (MAC), haploBMT PTCy,...
High-dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single-agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes pediatric young adult have not been reported. Between the years 2007 2013, 29 ages ≤21 of age treated at our institution high-risk underwent myeloablative T cell-replete BMT. Eleven received post-transplantation (PTCy) as GVHD...
Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem (hiPSC) occurs in only rare fractions (~0.001%-0.5%) donor transfected with non-integrating reprogramming factors. Pluripotency induction developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature augmented progenitor remains obscure, and its potential has not been fully explored for improving extremely slow pace...
Abstract Introduction: The survival rate of patients with Ewing sarcoma (ES) has seen slow improvement over the past several decades and remains dismal for those recurrent or metastatic disease. Initial clinical trials in relapsed/refractory ES single agent targeted therapies, combinations agents, have not yet improved patient outcomes. To overcome this barrier, Molecular Targeted Therapeutics Laboratory developed by silico design “first class” small molecule multikinase inhibitors (MKIs)...
Abstract Here, we report that the functionality of vascular progenitors (VP) generated from normal and disease-primed conventional human induced pluripotent stem cells (hiPSC) can be significantly improved by reversion to a tankyrase inhibitor-regulated naïve epiblast-like state. Naïve diabetic (N-DVP) differentiated patient-specific hiPSC (N-DhiPSC) possessed higher functionality, maintained greater genomic stability, harbored decreased lineage-primed gene expression, were more efficient in...
In examination of mechanisms regulating metabolic responses to growth hormone (GH), microarray analysis identified 561 probe sets showing time-dependent patterns expression in GH-treated 3T3-F442A adipocytes. Biological functions significantly over-represented among GH-regulated genes include regulators transcription at early times, and lipid biosynthesis, cholesterol mediators immune later times (48 h). One novel GH-induced gene encodes activating factor 3 (ATF3). Atf3 mRNA promoter...
The regulation of c-fos transcription by GH involves multiple factors, including CCAAT/enhancer binding protein (C/EBP) beta. Knockdown C/EBPbeta RNA interference prevents stimulation endogenous mRNA GH, indicating a key role for in GH-stimulated transcription. rapidly increases the occupancy both and p300 on promoter 3T3-F442A preadipocytes as indicated chromatin immunoprecipitation. transient presence anti-C/EBPbeta immunoprecipitate coincide with increase suggesting that nuclear complex...
Previous work showed that the adapter protein SH2B 1beta (SH2B1) (SH2-B) binds to activated form of nerve growth factor (NGF) receptor TrkA and is critical for both NGF-dependent neurite outgrowth maintenance. To identify SH2B1beta-regulated genes outgrowth, we performed microarray analysis control PC12 cells stably overexpressing SH2B1beta (PC12-SH2B1beta) or dominant-negative SH2B1beta(R555E) [PC12-SH2B1beta(R555E)]. NGF-induced expression Plaur Mmp10 was greatly enhanced in PC12-SH2B1beta...
For insight into transcriptional mechanisms mediating physiological responses to GH, data mining was performed on a profile of GH-regulated genes induced or inhibited at different times in highly responsive 3T3-F442A adipocytes. Gene set enrichment analysis indicated that are enriched pathways including phosphoinositide and insulin signaling suggested suppressor cytokine 2 (SOCS2) 3' kinase regulatory subunit p85alpha (Pik3r1) important targets. Model-based Chinese restaurant clustering...
Regulation of age-related changes in gene expression underlies many diseases. We previously discovered the first puberty-onset switch, stability element (ASE)/age-related increase (AIE)-mediated genetic mechanism for regulation. Here, we report that this mysterious amelioration abnormal bleeding seen hemophilia B Leyden. Transgenic mice robustly mimicking Leyden phenotype were constructed. Analysis these animals indicated ASE plays a central role disease. Human factor IX was reproducibly...
Abstract To date, there has been a lack of pediatric experience regarding the efficacy and tolerability immune checkpoint inhibitors after haploidentical hematopoietic stem cell transplant (HSCT). We present case 22‐year‐old female with multiple‐relapsed Hodgkin lymphoma (HL) who presented new relapse (post‐haplo) HSCT. Anti‐PD‐1 therapy nivolumab resulted in significant objective disease response clinical improvement without notable side effects, including absence graft‐versus‐host (GVHD)....
Little is known about the risk of post-COVID-19 multisystem inflammatory syndrome in children (MIS-C) setting childhood cancer.
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Mesenchymal to Epithelial Transition (MET) plasticity is critical cancer progression, and we recently showed that the OVOL transcription factors (TFs) are regulators of MET. Results work also posed hypothesis OVOLs impact MET in a range cancers. We now test this by developing model, Induced (OI-MET), sub-model (OI-MET-TF), characterize differential gene expression common prostate (PC) breast (BC). In OI-MET identified 739 genes differentially expressed both PC BC models. For set, found...