A5077326806- Acute Myeloid Leukemia Research
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Neutropenia and Cancer Infections
- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Mesenchymal stem cell research
- Hematological disorders and diagnostics
- Cell Adhesion Molecules Research
- Blood Coagulation and Thrombosis Mechanisms
- Retinoids in leukemia and cellular processes
- Bone and Joint Diseases
- Platelet Disorders and Treatments
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Cancer Treatment and Pharmacology
- Kruppel-like factors research
- Signaling Pathways in Disease
- Childhood Cancer Survivors' Quality of Life
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Venous Thromboembolism Diagnosis and Management
Medical College of Wisconsin
2016-2025
Versiti Blood Center of Wisconsin
2018-2024
Palmetto Hematology Oncology
2020
University of Wisconsin–Madison
2002-2016
Cornell University
2009-2014
Froedtert Hospital
2014
NewYork–Presbyterian Hospital
2009-2013
New York Hospital Queens
2009-2012
Rockefeller University
2010-2011
Presbyterian Hospital
2009-2011
Abstract Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development heterogeneity of human NK yet be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct populations in bone marrow blood, including one population expressing higher levels immediate early genes indicative a homeostatic activation. Functionally matured with high expression CX3CR1 , HAVCR2 (TIM-3), ZEB2 represents terminally differentiated status unique...
Treatment options for older patients with acute myeloid leukemia (AML) and relapsed/refractory AML are limited, outcomes poor. Decitabine, a hypomethylating agent, is active in myelodysplastic syndrome (MDS) AML, but its optimal dose schedule unknown. We report the efficacy safety of repeated 10-day cycles decitabine 20 mg/m2 administered intravenously over 1 h 52 newly diagnosed 102 patients. Repeated produced complete response (CR) 40% many whom had adverse prognostic features. The median...
Azacitidine/venetoclax is an active regimen in patients with newly diagnosed AML. However, primary or secondary resistance to azacitidine/venetoclax area of unmet need and overexpression MCL-1 suggested be a potential mechanism. Pevonedistat inhibits through activation NOXA, pevonedistat/azacitidine has previously shown activity To assess the tolerability efficacy adding pevonedistat relapsed/refractory AML, we conducted phase I multicenter openlabel study 16 adults Patients were treated...
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Abstract Peripheral nerve function depends on a regulated process of axon and Schwann cell development. cells interact with peripheral neurons to sort ensheath individual axons. Ablation laminin γ1 in the nervous system (PNS) arrests development prior radial sorting nerves laminin‐deficient animals are disorganized hypomyelinated. In this study, sciatic mice were treated syngenic murine adipose‐derived stem (ADSCs). ADSCs expressed vitro vivo following transplant into mutant nerves....
The serine protease tissue-type plasminogen activator (t-PA) initiates the fibrinolytic cascade and plays a significant role in motor learning, memory, neuronal cell death induced by excitotoxin ischemia. In system, serpin PAI-1 negatively regulates enzymatic activity of both single-chain two-chain t-PA (sct-PA tct-PA). central nervous neuroserpin (NSP) is thought to regulate activity. We report that although sct-PA tct-PA rapidly form acyl-enzyme complexes with NSP vitro, interactions are...
JMJD1C, a member of the lysine demethylase 3 family, is aberrantly expressed in mixed lineage leukemia (MLL) gene-rearranged (MLLr) leukemias. We have shown previously that JMJD1C required for self-renewal acute myeloid (AML) stem cells (LSCs) but not normal hematopoietic cells. However, domains within promote LSC are unknown. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) negative-selection screening and...
Background Outcomes of acute promyelocytic leukemia (APL) have significantly improved with the availability targeted agents. It remains unclear whether population-level outcomes APL over time. Methods Using SEER database, we identified patients aged ≥20 years pathologically confirmed diagnosed in 2000 through 2014 and who were actively followed. Patients stratified by diagnosis period into 3 groups (2000-2004, 2005-2009, 2010-2014) to assess temporal trends overall survival (OS),...
The transcriptional activation and repression during NK cell ontology are poorly understood. Here, using single-cell RNA-sequencing, we reveal a novel role for T-bet in suppressing the immature gene signature murine development. Based on transcriptome, identified five distinct clusters define their relative developmental maturity bone marrow. Transcriptome-based machine-learning classifiers revealed that half of mTORC2-deficient cells belongs to least mature cluster. Mechanistically, loss...
Background We sought to define the clinical and ultrastructure effects of ixabepilone (Ix), a microtubule-stabilizing chemotherapy agent on cutaneous sensory nerves investigate potential mitochondrial toxicity mechanism. Methods Ten breast cancer patients receiving Ix underwent total neuropathy score (TNSc) assessment, distal leg skin biopsies at cycle (Cy) 3 (80–90 mg/m2), Cy5 (160–190 Cy7 (>200 mg/m2) were compared 5 controls. Skin blocks processed for EM ultrastructural morphometry Remak...
Exogenous heparin exposure is the major risk factor for heparin-induced thrombocytopenia and thrombosis (HITT). To date, only five cases of 'spontaneous' HITT have been reported in literature. We report case a 60-year-old man who developed severe (15 000/μl) bilateral deep venous thromboses 10 days after knee replacement. There was no evidence upon review patient's preoperative postoperative medication history. Heparin: platelet factor-4 (PF4) antibodies were positive as serotonin release...
Retinal vein occlusion (RVO) and retinal artery (RAO) cause significant visual impairment. The role of thrombophilia cardiovascular testing is uncertain, optimal treatment strategies have not been determined. We reviewed medical records 39 patients with RVO RAO (23 women 16 men). Thrombophilia evaluations were performed outcomes reviewed. In all, 24 (61.5%) had at least 1 thrombophilia. Elevated factor VIII levels found in (n = 5) but RAO. There are no other differences thrombophilias...
ABSTRACT The rapid renewal of the epithelial gut lining is fuelled by stem cells that reside at base intestinal crypts. signal transduction pathways and morphogens regulate cell self-renewal differentiation have been extensively characterised. In contrast, although extracellular matrix (ECM) components form an integral part niche, their direct influence on cellular composition less well understood. We set out to systematically compare effect two ECM classes, interstitial basement membrane,...
Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown be safe effective. However, its efficacy GVHD when given only allo-HCT is unknown. We conducted a phase II study evaluate safety atorvastatin-based MRD (n = 30) or unrelated (MUD) 39) allo-HCT, enrolled in 2 separate cohorts. (40 mg/day) was administered along with standard...
Abstract Laminin-γ1 is required for early embryonic development; however, the need laminin-γ1 synthesis in adulthood unknown. A global and inducible mouse model of deficiency was generated to address this question. Genetic ablation Lamc1 gene adult mice rapidly lethal. Despite deletion tamoxifen-induced mutant mice, there minimal change total cardiac, pulmonary, hepatic or renal laminin protein. In contrast, significantly depleted small intestines, which showed crypt hyperplasia dissociation...
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders for which allogeneic transplantation (HCT) is currently the sole curative treatment. Epigenetic lesions considered major pathogenetic determinant in many cancers, and MDS, epigenetic-based interventions have emerged as life-prolonging therapies. However, impact epigenomic aberrations on HCT outcomes among patients with MDS not well understood. We hypothesized that signatures before undergoing serve...