A5055805166- Acute Myeloid Leukemia Research
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- SARS-CoV-2 and COVID-19 Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Platelet Disorders and Treatments
- COVID-19 Clinical Research Studies
- Protein Degradation and Inhibitors
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Cancer Genomics and Diagnostics
- Autophagy in Disease and Therapy
- Acute Lymphoblastic Leukemia research
- COVID-19 and healthcare impacts
- Multiple Myeloma Research and Treatments
- Cancer-related Molecular Pathways
- Single-cell and spatial transcriptomics
- Renal and related cancers
- T-cell and Retrovirus Studies
- Genomics and Chromatin Dynamics
- Injury Epidemiology and Prevention
- TGF-β signaling in diseases
- Disaster Response and Management
Albert Einstein College of Medicine
2017-2024
Montefiore Medical Center
2019-2024
The tumor suppressor p53 is often inactivated via its interaction with endogenous inhibitors mouse double minute 4 homolog (MDM4 or MDMX) 2 (MDM2), which are frequently overexpressed in patients acute myeloid leukemia (AML) and other cancers. Pharmacological disruption of both these interactions has long been sought after as an attractive strategy to fully restore p53-dependent activity cancers wild-type p53. Selective targeting this pathway thus far limited MDM2-only small-molecule...
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that not eliminated by conventional therapies. Transcriptomic analysis of progenitor populations in MDS AML demonstrated overexpression STAT3 was validated an independent cohort. predictive a shorter survival worse clinical features large High expression signature CD34+ similar to known preleukemic gene signatures. Functionally, inhibition clinical, antisense oligonucleotide,...
Background: Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. Many healthcare regulatory agencies recommend administering ‘booster’ doses of vaccines beyond the standard two-dose series, for this group patients. Therefore, studying efficacy these additional vaccine against SARS-CoV-2 variants concern is utmost importance in immunocompromised patient population Methods: We conducted a prospective single arm clinical trial enrolling cancer that...
Abstract Cytosine hypermethylation in and around DNA-binding sites of master transcription factors, including PU.1, occurs aging hematopoietic stem cells following acquired loss-of-function mutations DNA methyl-cytosine dioxygenase ten–eleven translocation-2 (TET2), albeit functional relevance has been unclear. We show that Tet2-deficient mouse progenitor undergo malignant transformation upon compromised gene regulation through heterozygous deletion an upstream regulatory region (UREΔ/WT)...
Therapy-related acute myeloid leukemia and myelodysplastic syndromes (t-AML/t-MDS) are secondary hematologic malignancies associated with poor prognosis, warranting insights into their predisposing conditions cells of origin. We identified patients myeloma who developed t-AML/t-MDS analyzed stem progenitor collected years before the onset disease. demonstrate that aberrant high CD123 expression can be detected long overt leukemia. Rigorous sorting, followed by targeted sequencing, resulted...
<title>Abstract</title> Malignancies can become reliant on glutamine as an alternative energy source and a facilitator of aberrant DNA methylation, thus implicating glutaminase (GLS) potential therapeutic target. We demonstrate preclinical synergy telaglenastat (CB-839), selective GLS inhibitor, when combined with azacytidine (AZA), <italic>in vitro</italic> vivo</italic>, followed by phase Ib/II study the combination in patients advanced MDS. Treatment telaglenastat/AZA led to ORR 70%...
Bone marrow resident and rarely dividing haematopoietic stem cells (HSC) harbour an extensive self-renewal capacity to sustain life-long blood formation; 1–5 albeit their function declines during ageing. 6, 7 Various molecular mechanisms confer cell identity, ensure long-term maintenance are known be deregulated in aged cells. 8, 9 How these programs coordinated, particularly division, what triggers ageing-associated dysfunction has been unknown. Here, we demonstrate that HSC, containing the...
Abstract Cancer patients show increased morbidity with COVID-19 and need effective immunization strategies. We demonstrate that a 3 rd dose of vaccine leads to seroconversion in 57% were seronegative after primary vaccination. The immune response is durable as assessed by anti-S antibody titers, T-cell activity neutralization against wild-type SARS-CoV2 BA1.1.529 at 6 months follow up. A subset severely immunocompromised hematologic malignancy unable mount adequate the treated 4 th...
Thrombocytopenia, prevalent in the majority of patients with myeloid malignancies, such as myelodysplastic syndrome (MDS) or acute leukemia (AML), is an independent adverse prognostic factor. Azacitidine (AZA), a mainstay therapeutic agent for stem cell transplant–ineligible MDS/AML, often transiently induces further aggravates disease-associated thrombocytopenia by unknown mechanism. Here, we uncover critical role type-I interferon (IFN-I) signaling activation suppressing megakaryopoiesis...
<div>Abstract<p>Cytosine hypermethylation in and around DNA-binding sites of master transcription factors, including PU.1, occurs aging hematopoietic stem cells following acquired loss-of-function mutations DNA methyl-cytosine dioxygenase ten–eleven translocation-2 (TET2), albeit functional relevance has been unclear. We show that <i>Tet2</i>-deficient mouse progenitor undergo malignant transformation upon compromised gene regulation through heterozygous deletion an...
Supplementary Figure from PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i>-Deficient Hematopoiesis Malignant Transformation
Supplementary Data from PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i>-Deficient Hematopoiesis Malignant Transformation
Supplementary Data from PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i>-Deficient Hematopoiesis Malignant Transformation
<div>Abstract<p>Cytosine hypermethylation in and around DNA-binding sites of master transcription factors, including PU.1, occurs aging hematopoietic stem cells following acquired loss-of-function mutations DNA methyl-cytosine dioxygenase ten–eleven translocation-2 (TET2), albeit functional relevance has been unclear. We show that <i>Tet2</i>-deficient mouse progenitor undergo malignant transformation upon compromised gene regulation through heterozygous deletion an...
Supplementary Figure from PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i>-Deficient Hematopoiesis Malignant Transformation
Supplementary Data from PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i>-Deficient Hematopoiesis Malignant Transformation
Supplementary Data from PU.1-Dependent Enhancer Inhibition Separates <i>Tet2</i>-Deficient Hematopoiesis Malignant Transformation