A5001138042- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Acute Myeloid Leukemia Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Brain Metastases and Treatment
- interferon and immune responses
- NF-κB Signaling Pathways
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Tendon Structure and Treatment
- Bacteriophages and microbial interactions
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Chronic Myeloid Leukemia Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- CRISPR and Genetic Engineering
- Kruppel-like factors research
- Sports injuries and prevention
- Drug-Induced Adverse Reactions
- Enzyme Structure and Function
- Developmental Biology and Gene Regulation
University of Maryland, Baltimore
2017-2024
Global Virus Network
2023-2024
Columbia University Irving Medical Center
2015-2022
VA Maryland Health Care System
2021-2022
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2018
Center for Neuroscience and Regenerative Medicine
2018
Cancer Genetics (United States)
2015
Institut thématique Génétique, génomique et bioinformatique
2015
Columbia University
2012-2014
A balance between quiescence and proliferation is critical for proper maintenance of the hematopoietic stem cell (HSC) pool. Although a lot known about hematopoiesis, molecular mechanisms that control HSC remain largely unknown. The ubiquitin-editing enzyme A20 functions as central regulator inflammation adaptive immunity. Here, we show deficiency in system causes anemia, lymphopenia, postnatal lethality. Lack HSCs results diminished pool size, impaired radioprotection, defective...
Constitutive activation of the canonical NF-κB pathway has been associated with a variety human pathologies. However, molecular mechanisms through which affects hematopoiesis remain elusive. Here, we demonstrate that deregulated signals in hematopoietic stem cells (HSCs) cause complete depletion HSC pool, pancytopenia, bone marrow failure, and premature death. IKK2 HSCs leads to impaired quiescence loss function. Gene set enrichment analysis (GSEA) identified an induction "erythroid...
Identifying physiological roles of specific signaling pathways that regulate Hematopoietic Stem Cell (HSC) functions may lead to new treatment strategies and therapeutic interventions for hematologic disorders. Here, we provide genetic evidence constitutive activation NF-kB in hematopoietic stem cells (HSCs) results reduced pool size, repopulation capacities quiescence HSCs. Global transcriptional profiling bioinformatics studies identified loss 'stemness' 'quiescence' signatures HSCs with...
Exaggerated inflammation and cytokine storm are hallmark features of influenza A virus (IAV)-induced respiratory diseases. While previous studies unequivocally demonstrated the pathophysiological consequences (multiorgan failure) IAV-associated storm, it remains unknown if IAV-induced systemic impacts fitness differentiation immune cells from hematopoietic stem (HSCs). Our data on lethal IAV-infected C57BL/6 wildtype mice after 10 days infection indicated reduced monocyte- lymphocyte- counts...
Inflammatory signals have been shown to play a critical role in controlling the maintenance and functions of hematopoietic stem cells (HSCs). While significance inflammation hematopoiesis has begun unfold, molecular mechanisms players that govern this mode HSC regulation remain largely unknown. The E3 ubiquitin ligase A20 considered as central gatekeeper inflammation. Here, we specifically depleted multi-potent progenitors (MPPs) studied its impact on hematopoiesis. Our data suggest lack...
Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary remain incompletely understood. In particular, the impact TBI on differentiation and maintenance dendritic cells (DCs), which are regarded as most professional antigen presenting immune system, remains completely unknown. Here, we report that DC-differentiation, functions altered day 3 7 after TBI.Long bones, spleen, peripheral lymph nodes (pLNs), mesenteric (mLNs), liver, lungs, skin blood were collected from...
Well-controlled repair mechanisms are involved in the maintenance of genomic stability, and their failure can precipitate DNA abnormalities elevate tumor risk. In addition, microenvironment, enriched with factors inducing oxidative stress affecting cell cycle checkpoints, intensifies damage when pathways falter. Recent research has unveiled associations between certain bacteria, including Mycoplasmas , various cancers, causative mechanism(s) under active investigation. We previously showed...
Abstract Background Chemotherapy is a primary treatment for cancer, but its efficacy often limited by cancer-associated bacteria (CAB) that impair tumor suppressor functions. Our previous research found Mycoplasma fermentans DnaK, chaperone protein, impairs p53 activities, which are essential most anti-cancer chemotherapeutic responses. Methods To investigate the role of DnaK in chemotherapy, we treated cancer cell lines with M. and then commonly used p53-dependent drugs (cisplatin 5FU). We...
Deregulated notch signaling has been associated with human pathobiology. However, functions of pathways in hematopoiesis remain incompletely understood. Here, we ablated canonical pathways, through genetic deletion Rbpj, hematopoietic stem cells (HSCs). Our data identified that loss results normal adult HSC pool, at steady state conditions. maintenance and response to radiation-, chemotherapy-, cytokine- induced stress were compromised the absence notch. Rbpj deficient HSCs exhibit decreased...
Abstract Inflammation and inflammatory cytokines have been shown to exert both positive negative effects on hematopoietic stem cells (HSCs) hematopoiesis. While the significance of inflammation driven hematopoiesis has begun unfold, molecular players that regulate this phenomenon remain largely unknown. In present study, we identified A20 as a critical regulator controlled cell fate decisions HSCs. deficiency in HSCs leads increased differentiation myeloid myeloproliferation. Analysis...
The human microbiota affects critical cellular functions, although the responsible mechanism(s) is still poorly understood. In this regard, we previously showed that Mycoplasma fermentans DnaK, an HSP70 chaperone protein, hampers activity of important proteins for DNA integrity. Here, describe a novel DnaK knock-in mouse model generated in our laboratory to study effect M. expression vivo. By using array-based comparative genomic hybridization assay, demonstrate exposure was associated with...
Hematopoietic stem cells (HSCs) are capable of both self-renewing throughout the lifetime an organism and differentiating into all lineages blood system. A proper balance between quiescence proliferation is critical for self-renewal functions HSCs. The choice HSCs to remain quiescent or enter has been tightly regulated by a variety cell intrinsic extrinsic pathways. Identifying molecular players that control HSC may lead new treatment strategies therapeutic interventions hematologic...
Dendritic cells (DCs) play pivotal roles in initiating and shaping both innate adaptive immune responses. The spatiotemporal expression of transcription factor networks activation specific signal transduction pathways determine the specification, distribution differentiation DC subsets. Even though pioneering studies have established indispensable for catalytic subunits (p110δ p110γ) cells, functions regulatory subunits, particularly Class I PI3K, within hematopoietic system remain...
Fibroadipogenic progenitor (FAP) cells are implicated as a major source of fatty infiltration (FI) in murine rotator cuff (RC) injury, but FAP cell response after RC tear rabbit model is unknown. This study determined whether changes count an predate muscle degeneration clinically relevant model. We hypothesized increases correlate temporally with degeneration. New Zealand white rabbits (n = 26) were evaluated at 1, 2, 4, and 6 weeks unilateral full-thickness tenotomy supraspinatus...
Abstract Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary remain incompletely understood. In particular, the impact TBI on differentiation and maintenance dendritic cells (DCs), remains completely unknown. Here, we report that DC- differentiation, functions are altered at both early late phases TBI. Our studies identify that; 1. frequencies absolute numbers DCs in spleen BM acute TBI; 2. surface expression key molecules involved antigen presentation were...
Abstract Chronic inflammation has been strongly associated with tumor progression, but the underlying mechanisms remain elusive. Our previous studies have achieved important new insights into key regulatory mechanism in immune system mediated by ubiquitin ligase, Itch, whose deficiency results inflammatory disorders and pulmonary (Venuprasad K et al. Nat. Immunol. 2008, Venuprasad K. J.Clin. Invest. 2004). We demonstrate that E3 ligase Itch deubiquitinase Cyld formed a complex via...
Abstract Basophils are one of the major players in pathophysiology allergy related immune disorders. In spite their key roles autoimmune and inflammatory disorders humans, molecular mechanisms that control basophils remain largely unknown. Therefore we have been involved elucidating biochemical through which development functions controlled system. this study, utilized Itch deficient mouse as a model system for understanding biology Basophils. is an E3 ubiquitin ligase belongs to HECT...
In the recent years, it has become increasingly evident that hematopoietic stem cells (HSCs) are directly involved in recognition of both acute and chronic infections. HSCs sense immune insults by cell intrinsic, through pattern receptors (PRRs), extrinsic, mediated mainly pro-inflammatory cytokines, mechanisms. However, prolonged exposure to inflammatory conditions results defective differentiation cells. Even though earlier studies suggested a tight control on signals is essential for...
Abstract Hematopoiesis is a complex process that regulated at multiple levels and through both intrinsic extrinsic regulators. Trim28 multidomain protein functions as transcription factor E3 ubiquitin ligase. Recent studies have established the pivotal roles of in variety pathophysiologic processes including inflammation, autoimmune disorders, viral pathogenesis, cancer, tumor microenvironment epithelial-to- mesenchymal transition. However, importance early hematopoiesis, particularly...
Abstract Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary remain incompletely understood. In particular, the impact TBI on differentiation and maintenance dendritic cells (DCs), remains completely unknown. Here, we report that DC- differentiation, functions are altered at both early late phases TBI. Our studies identify that; 1. frequencies absolute numbers DCs in spleen BM acute TBI; 2. surface expression key molecules involved antigen presentation were...
Abstract Pathophysiological consequences of traumatic brain injury (TBI) mediated secondary remain incompletely understood. In particular, the impact TBI on differentiation and maintenance dendritic cells (DCs), remains completely unknown. Here, we report that DC-differentiation, functions are altered at both early late phases TBI. Our studies identify that; 1. frequencies absolute numbers DCs in spleen BM acute TBI; 2. surface expression key molecules involved antigen presentation were...