A5006168813- Acute Myeloid Leukemia Research
- Immune cells in cancer
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Hematopoietic Stem Cell Transplantation
- Chronic Myeloid Leukemia Treatments
- Inflammation biomarkers and pathways
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- Retinoids in leukemia and cellular processes
- Single-cell and spatial transcriptomics
- Histone Deacetylase Inhibitors Research
- Lymphoma Diagnosis and Treatment
- Cancer-related gene regulation
- Aquaculture disease management and microbiota
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Acute Lymphoblastic Leukemia research
- Mesenchymal stem cell research
- Neutropenia and Cancer Infections
- Cancer Immunotherapy and Biomarkers
The Ohio State University
2007-2025
The Ohio State University Wexner Medical Center
2006-2024
Comprehensive Blood & Cancer Center
2024
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2022-2023
Harvard University
2014-2017
Dana-Farber Cancer Institute
2015-2017
Boston Children's Hospital
2015-2017
Harvard Stem Cell Institute
2017
Howard Hughes Medical Institute
2017
Boston Children's Museum
2016
Blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome–positive (Ph1-positive) acute lymphocytic (ALL) are 2 fatal BCR/ABL-driven leukemias against which Abl kinase inhibitors fail to induce a long-term response. We recently reported that functional loss of protein phosphatase 2A (PP2A) activity is important for CML blastic transformation. assessed the therapeutic potential PP2A activator FTY720 (2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol hydrochloride), an...
A significant challenge to overcome in pancreatic ductal adenocarcinoma (PDAC) is the profound systemic immunosuppression that renders this disease non-responsive immunotherapy. Our supporting data provide evidence CD200, a regulator of myeloid cell activity, expressed PDAC microenvironment. Additionally, myeloid-derived suppressor cells (MDSC) isolated from patients with express elevated levels CD200 receptor (CD200R). Thus, we hypothesize expression microenvironment limits responses...
Abstract Richter’s Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) implicated in lymphomagenesis, but its role CLL or RT unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 patients with to RT. Furthermore, mice B-specific overexpression hPRMT5 develop B-lymphoid expansion increased risk death, Eµ-PRMT5/TCL1 double...
Mutations and deletions in TP53 are associated with adverse outcomes patients myeloid malignancies developing improved therapies for TP53-mutant leukemias is of urgent need. Here we identify mutations TET2 as the most common co-occurring mutation mutant acute leukemia (AML) patients. In mice, combined hematopoietic-specific deletion resulted enhanced self-renewal compared to either gene alone. Tp53/Tet2 double knockout mice developed serially transplantable AML. Both AML TET2/TP53...
IL-15 is required for NK cell development and homeostasis in vivo. Because presented trans via its high-affinity IL-15Ralpha-chain to cells expressing the IL-15Rbetagamma complex, we postulated that certain IL-15-bearing must be homeostasis. Using IL-15(WT/WT) IL-15(-/-) mice, bone marrow chimeras with normal cellularity, a selective depletion of CD11c(hi) dendritic (DCs), demonstrate ablation resting DC population results highly significant decrease absolute number mature cells. In...
The microenvironment is an important regulator of hematopoietic stem and progenitor cell (HSPC) biology. Recent advances marking fluorescent HSPCs have allowed exquisite visualization in the caudal tissue (CHT) developing zebrafish. Here, we show that chemokine cxcl8 its receptor, cxcr1, are expressed by zebrafish endothelial cells, identify cxcl8/cxcr1 signaling as a positive HSPC colonization. Single-cell tracking experiments demonstrated this result increases HSPC–endothelial “cuddling,”...
Monokines (i.e., interleukin [IL]-12, -18, and -15) induce natural killer (NK) cells to produce interferon-γ (IFN-γ), which is a critical factor for immune surveillance of cancer monocyte clearance infection. We show that SET, potent inhibitor protein phosphatase type 2A (PP2A) activity, highly expressed in human CD56bright NK cells, more IFN-γ than CD56dim cells. SET was up-regulated upon monokine stimulation primary Furthermore, ectopic overexpression significantly enhanced gene expression...
An increased incidence of cardiovascular complications has been documented in recipients allogeneic hematopoietic stem cell transplantation (HSCT). Despite this, little is known about the risk factors for hyperlipidemia or role lipid-lowering therapy early after transplantation. We performed a retrospective analysis all patients who underwent HSCT at Dana-Farber Cancer Institute from 1998 to 2008 and survived more than 100 days. The hypercholesterolemia hypertriglyceridemia first 2 years was...
Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor attributed, in part, to limited and ineffective treatments for patients metastatic disease, highlighting need identify molecular drivers pancreatic target more effective treatment. CD200 glycoprotein that interacts the receptor CD200R elicits immunosuppressive response. Overexpression has been associated differential outcomes, depending on tumor type. In context cancer, we have previously reported...
Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have poor treatment outcomes when treated traditional chemoimmunotherapy. Superior been observed the 2 CAR-T cell products approved by US FDA; tisagenlecleucel (CTL109) and axicabtagene ciloleucel (Axi-cel) 12 months overall survival rates of 49% 59% respectively. The major acute toxicities these therapies are cytokine release syndrome (CRS) neurotoxicity. incidence grade 3 or higher neutropenia, anemia, thrombocytopenia...
Altered hematopoietic stem cell (HSC) fate underlies primary blood disorders but microenvironmental factors controlling this are poorly understood. Genetically barcoded genome editing of synthetic target arrays for lineage tracing (GESTALT) zebrafish were used to screen expressed by the sinusoidal vascular niche that alter phylogenetic distribution HSC pool under native conditions. Dysregulated expression protein kinase C delta (PKC-δ, encoded prkcda) increases number clones up 80% and...
Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma, and patients who relapse on targeted therapies have poor prognosis. Protein arginine methyltransferase 5 (PRMT5), enzyme essential for transformation, drives multiple oncogenic pathways overexpressed in MCL. Despite the antitumor activity of PRMT5 inhibition (PRT-382/PRT-808), drug resistance was observed a patient-derived xenograft (PDX) MCL model. Decreased survival mice engrafted with these inhibitor-resistant cells...
There have been substantial advances in understanding the events that regulate gene expression at cellular and molecular level; however, there has limited progress integrating this information to understand how biological systems function vivo. For example, anti-inflammatory cytokine IL-10 is thought down-regulate effects of pro-inflammatory IFN-gamma on monocyte activation following LPS stimulation. However, often-postulated reciprocal regulation by not studied Here we demonstrate least two...
Background: Immune-compromised individuals are at increased risk for developing aggressive Epstein-Barr virus (EBV)–associated lymphoproliferative disorders after primary EBV infection or reactivation of a preexisting latent infection. We evaluated the effect depsipeptide, histone deacetylase inhibitor, on EBV-positive lymphoblastoid cell lines (LCLs) and Burkitt lymphoma in mouse model explored its mechanism action vitro. Methods: studied EBV-transformed LCLs, which express III (Lat-III)...