A5076989555- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- Immune cells in cancer
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Earthquake Detection and Analysis
- Erythrocyte Function and Pathophysiology
- Chemokine receptors and signaling
- Polyamine Metabolism and Applications
- Sirtuins and Resveratrol in Medicine
- Autophagy in Disease and Therapy
- Cancer Research and Treatments
- Developmental Biology and Gene Regulation
- Histone Deacetylase Inhibitors Research
- Childhood Cancer Survivors' Quality of Life
- Ion Channels and Receptors
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chemical Synthesis and Analysis
- Cancer, Hypoxia, and Metabolism
- Biopolymer Synthesis and Applications
Princess Margaret Cancer Centre
2020-2025
University Health Network
2020-2025
University of Toronto
2021-2025
Institute of Geosphere Dynamics
2023-2024
Russian Academy of Sciences
2024
New York University
2012-2023
NYU Langone Health
2021
National Cancer Institute
2011-2020
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2019-2020
University Hospital of Bern
2019
The bone marrow (BM) microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC) pool (Morrison Spradling, 2008Morrison S.J. Spradling A.C. Stem niches: mechanisms that promote maintenance throughout life.Cell. 2008; 132: 598-611Abstract Full Text PDF PubMed Scopus (1441) Google Scholar). We have previously demonstrated endothelial support proper regeneration system following myeloablation (Butler et...
Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient trigger HIF1α damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses functional studies reveal retinoic acid-related orphan receptor γt
Abstract The αβ T cell receptor (TCR) repertoire on mature cells is selected in the thymus, but basis for thymic selection of MHC-restricted TCRs from a randomly generated pre-selection not known. Here we perform comparative sequence analyses and post-selection TCR multiple MHC-sufficient MHC-deficient mouse strains, find that MHC-independent are primarily distinguished by features their non-germline CDR3 regions, with many sequences compatible MHC-binding. Thymic largely unconstrained,...
Outcomes for patients with acute myeloid leukemia (AML) remain poor due to the inability of current therapeutic regimens fully eradicate disease-initiating stem cells (LSC). Previous studies have demonstrated that oxidative phosphorylation (OXPHOS) is an essential process targetable in LSC. Sirtuin 3 (SIRT3), a mitochondrial deacetylase multi-faceted role metabolic regulation, has been shown regulate OXPHOS cancer models; however, it not yet studied context Thus, we sought identify if SIRT3...
T-lineage acute lymphoblastic leukemia (ALL) is an aggressive cancer comprising diverse subtypes that are challenging to stratify using conventional immunophenotyping. To gain insights into subset-specific therapeutic vulnerabilities, we performed integrative multiomics analysis of bone marrow samples from newly diagnosed T cell ALL, early precursor and T/myeloid mixed phenotype leukemia. Leveraging cellular indexing transcriptomes epitopes in conjunction with receptor sequencing, identified...
Multiple myeloma (MM) is a plasma cell malignancy characterized by the presence of multiple foci in skeleton. These distinct tumor represent cycles growth and dissemination that seed new clusters drive disease progression. By using an intratibial Vk*MYC murine model, we found CD169+ radiation-resistant tissue-resident macrophages (MPs) were critical for early Depletion these MPs had no effect on proliferation, but it did reduce egress from bone marrow (BM) its spread to other bones. as...
Despite improvements in outcomes for children with B- and T-cell acute lymphoblastic leukemia (B-ALL T-ALL), patients resistant or relapsed disease fare poorly. Previous studies have demonstrated the essential role of cyclin D3 T-ALL initiation progression that targeting CDK4/6-cyclin D complex can suppress proliferation, leading to efficient cell death animal models. Studies other malignancies, suggest schedule is important when combining CDK4/6 inhibitors (CDKi) cytotoxic agents. Based on...
Acute myeloid leukemia (AML) is a devastating disease initiated and maintained by rare subset of cells called stem (LSCs). LSCs are responsible for driving relapse, making the development new therapeutic strategies to target urgently needed. The use mass spectrometry–based metabolomics profiling has enabled discovery unique targetable metabolic properties in LSCs. However, we do not have comprehensive understanding metabolite differences between their normal counterparts, hematopoietic...
T cell acute lymphoblastic leukemia (T-ALL) is commonly associated with activating mutations in the NOTCH1 pathway. Recent reports have shown a link between signaling and intracellular Ca2+ homeostasis T-ALL. Here, we investigate role of store-operated entry (SOCE) mediated by channel ORAI1 its activators STIM1 STIM2 Deletion leukemic cells abolishes SOCE significantly prolongs survival mice NOTCH1-dependent model The advantage unrelated to burden but SOCE-dependent ability malignant...
Abstract Immature thymocytes that are positively selected based upon their response to self-peptide-MHC complexes develop into mature T cells not overtly reactive those same complexes. Developmental tuning is the active process through which TCR-associated signaling pathways of single-positive attenuated respond appropriately peptide-MHC molecules will be encountered in periphery. In this study, we explore mechanisms regulate CD4+ MHC class II thymic medulla. Experiments with murine BM...
Abstract During normal T cell development in the thymus, αβ TCRs signal immature thymocytes to differentiate into mature cells by binding peptide–MHC ligands together with CD4/CD8 coreceptors. Conversely, MHC and coreceptor-deficient mice, thymus generates expressing MHC-independent that recognize native conformational epitopes rather than linear antigenic-peptides presented MHC. To date, no structural information of is available, their recognition non-MHC ligand remains unknown. our...