A5003182946- Synthesis and biological activity
- Quinazolinone synthesis and applications
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Genomics, phytochemicals, and oxidative stress
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Pharmacological Effects of Natural Compounds
- NF-κB Signaling Pathways
- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Synthesis and Biological Evaluation
- Chemokine receptors and signaling
- Retinoids in leukemia and cellular processes
- Curcumin's Biomedical Applications
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Phagocytosis and Immune Regulation
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Hemoglobinopathies and Related Disorders
- Melanoma and MAPK Pathways
- Chronic Lymphocytic Leukemia Research
Center for Discovery
2020-2025
Hackensack Meridian Health
2022-2025
Hackensack University Medical Center
2020-2024
Georgetown University
2022-2024
Memorial Sloan Kettering Cancer Center
2010-2024
Brigham and Women's Hospital
2005-2014
Florida College
2005-2014
Cornell University
2014
University of Florida
2005-2014
Harvard University
2014
Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that proto-oncogene LRF plays an essential role versus cell-fate decision. We demonstrate is key for instructing early progenitors mice develop lineage by repressing cell-instructive signals produced signal protein, Notch. propose a new model commitment, acts as master regulator of cell's determination lineage.
Paradoxical to its importance for generating a diverse T cell repertoire, thymic function progressively declines throughout life. This process has been at least partially attributed the effects of sex steroids, and their removal promotes enhanced thymopoiesis recovery from immune injury. We show that one mechanism by which steroids influence is through direct inhibition in cortical epithelial cells (cTECs) Delta-like 4 (Dll4), Notch ligand crucial commitment differentiation progenitors...
Preventing unfavorable GVHD without inducing broad suppression of the immune system presents a major challenge allogeneic hematopoietic stem cell transplantation (allo-HSCT). We developed novel strategy to ameliorate while preserving graft-versus-tumor (GVT) activity by small molecule-based inhibition NF-κB family member c-Rel. Underlying mechanisms included reduced alloactivation, defective gut homing, and impaired negative feedback on interleukin (IL)-2 production, resulting in optimal...
NF-κB plays a variety of roles in oncogenesis and immunity that may be beneficial for therapeutic targeting, but strategies to selectively inhibit exert antitumor activity have been elusive. Here, we describe IT-901, bioactive naphthalenethiobarbiturate derivative potently inhibits the subunit c-Rel. IT-901 suppressed graft-versus-host disease while preserving graft-versus-lymphoma during allogeneic transplantation. Further preclinical assessment treatment human B-cell lymphoma revealed...
IT-901 is a novel and selective NF-κB inhibitor with promising activity in pre-clinical models. Here we show that treatment of chronic lymphocytic leukemia cells (CLL) effectively interrupts transcriptional activity. CLL exposed to the drug display elevated mitochondrial reactive oxygen species, which damage mitochondria, limit oxidative phosphorylation ATP production, activate intrinsic apoptosis. Inhibition signaling stromal myeloid cells, both tumor-supportive elements, fails induce...
Abstract Aberrant expression of high-mannose glycans (Man9) and phosphatidylserine (PS) lipids on tumor cells represents a promising immunotherapeutic target for cancer. Previously, we demonstrated that Man9xPS targeting T cell engager molecule significantly improved control survival in acute myeloid leukemia (AML) mouse models. Building these findings, now report the development CAR therapy designed to enhance specificity overcome challenges seen with protein-antigen escape mutational...
Summary Growth factor‐independent 1B ( GFI1B ) is a transcription factor essential for the development and differentiation of erythroid megakaryocytic lineages. We evaluated expression in erythroleukaemia leukaemia, as well patients with other subtypes acute myeloid leukaemia (AML), lymphoblastic (ALL), chronic (CML), myelodysplastic syndrome (MDS), severe aplastic anaemia (SAA), myelofibrosis metaplasia (MMM) healthy volunteers. was increased at least threefold P < 0·01 compared...
Previous studies demonstrated selective inhibition of the BCR-ABL (breakpoint cluster region-Abelson murine leukemia oncogene) tyrosine kinase by RNA interference in leukemic cells. In this study, we evaluated effect small interfering (siRNA) and GFI1B siRNA silencing on chronic myeloid (CML) cells blast crises. The gene was mapped to chromosome 9 is, therefore, located downstream translocation CML Co-transfection dramatically decreased cell viability significantly induced apoptosis...
Alloreactive T cells are crucial for graft-versus-host disease (GVHD) pathophysiology, and modulating their trafficking patterns has been efficacious in ameliorating experimental disease. We report this paper that P-selectin, a glycoprotein found on resting inflamed endothelium, is important donor alloreactive into GVHD target organs, such as the intestines skin. Compared with wild-type (WT) recipients of allogeneic bone marrow transplantation, P-selectin(-/-) exhibit decreased mortality...
Restoring T cell competence is a significant clinical challenge in patients whose thymic function severely compromised due to age or cytoreductive conditioning. Here, we demonstrate mice that mesenteric LNs (MLNs) support extrathymic development euthymic and athymic recipients of bone marrow transplantation (BMT). Furthermore, aged murine BMT recipients, the contribution MLNs generation cells was maintained, while thymus significantly impaired. Thymic impairment resulted proportional...