A5010328012- Acute Lymphoblastic Leukemia research
- Genetics and Neurodevelopmental Disorders
- Transgenic Plants and Applications
- Pharmaceutical studies and practices
- Autism Spectrum Disorder Research
- Hemoglobinopathies and Related Disorders
- Advanced Differential Geometry Research
- Iron Metabolism and Disorders
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Ophthalmology and Eye Disorders
- Prenatal Screening and Diagnostics
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Hemispheric Asymmetry in Neuroscience
- Cancer-related gene regulation
- Childhood Cancer Survivors' Quality of Life
- RNA modifications and cancer
- Wnt/β-catenin signaling in development and cancer
- Ubiquitin and proteasome pathways
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
- BRCA gene mutations in cancer
- Blood donation and transfusion practices
Muhimbili University of Health and Allied Sciences
2023-2025
Boston Children's Hospital
2016-2023
Harvard University
2018-2023
Center for Human Genetics
2019
KU Leuven
2019
VIB-KU Leuven Center for Cancer Biology
2019
Boston Children's Museum
2016
Doheny Eye Institute
2004
Abstract Colorectal cancer is driven by mutations that activate canonical WNT/β-catenin signaling, but inhibiting WNT has significant on-target toxicity, and there are no approved therapies targeting dominant oncogenic drivers. We recently found activating a β-catenin–independent branch of signaling inhibits GSK3-dependent protein degradation induces asparaginase sensitivity in drug-resistant leukemias. To test predictions from our model, we turned to colorectal because these cancers can...
Despite progress in healthcare services for individuals living with sickle cell disease (SCD) Africa, substantial gaps remain advanced treatments SCD. To help address this burden, Tanzania has established one of the largest single-centre SCD programmes world and developed an therapy programme focused on patient engagement advocacy, clinical activities involving exchange blood transfusion (ExBT) haematopoietic stem transplant (HSCT), gene (GT) preparedness, enabling partnerships. This report...
The tendency of mitochondria to undergo or resist BCL2-controlled apoptosis (so-called mitochondrial priming) is a powerful predictor response cytotoxic chemotherapy. Fully exploiting this finding will require unraveling the molecular genetics underlying phenotypic variability in priming. Here, we report that resistance T cell acute lymphoblastic leukemia (T-ALL) mediated by inactivation polycomb repressive complex 2 (PRC2). In T-ALL clinical specimens, loss-of-function mutations PRC2 core...
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Resistance to asparaginase is a common clinical problem, whose biologic basis poorly understood. We hypothesized, from the concept of synthetic lethality, that gain-of-fitness alterations in drug-resistant cells had conferred survival advantage could be exploited therapeutically. Using genome-wide CRISPR/Cas9 screen T-ALL, we found negative regulators Wnt signaling were selectively depleted upon treatment with asparaginase. pathway activation induced profound sensitivity distinct...
SUMMARY Resistance to asparaginase, an antileukemic enzyme that depletes asparagine, is a common clinical problem. Using genome-wide CRISPR/Cas9 screen, we found synthetic lethal interaction between Wnt pathway activation and asparaginase in acute leukemias resistant this enzyme. induced sensitivity distinct treatment-resistant subtypes of leukemia, including T-lymphoblastic, hypodiploid B-lymphoblastic, myeloid leukemias, but not normal hematopoietic progenitors. Sensitization was mediated...
<div>Abstract<p>Colorectal cancer is driven by mutations that activate canonical WNT/β-catenin signaling, but inhibiting WNT has significant on-target toxicity, and there are no approved therapies targeting dominant oncogenic drivers. We recently found activating a β-catenin–independent branch of signaling inhibits GSK3-dependent protein degradation induces asparaginase sensitivity in drug-resistant leukemias. To test predictions from our model, we turned to colorectal because...
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Abstract Background: Fetal haemoglobin (HbF) remains a major sickle cell disease modifier. The mechanism of HbF synthesis has been studied for several decades with the intention increasing interventions (SCD), including drugs. However, complex is influenced by multiple genetic factors interacting environmental factors. In order to capture useful information, especially limited resources, one carefully design study. This includes choosing relevant participants, correct phenotyping, choice...
<div>Abstract<p>Colorectal cancer is driven by mutations that activate canonical WNT/β-catenin signaling, but inhibiting WNT has significant on-target toxicity, and there are no approved therapies targeting dominant oncogenic drivers. We recently found activating a β-catenin–independent branch of signaling inhibits GSK3-dependent protein degradation induces asparaginase sensitivity in drug-resistant leukemias. To test predictions from our model, we turned to colorectal because...
Abstract The tendency of mitochondria to undergo or resist BCL2-controlled apoptosis (so-called mitochondrial priming) is a powerful predictor the outcome cytotoxic chemotherapy for cancer. To fully exploit this finding, it will be important understand molecular genetic contexts responsible relative priming chemotherapy-sensitive versus resistant cell populations. Here we report that resistance in T-cell acute lymphoblastic leukemia (T-ALL) mediated by inactivation polycomb repressive...
Background: Intensification of asparaginase‐based therapy has improved outcomes for several subtypes acute leukemia, but the development treatment resistance a poor prognosis, and effective therapeutic options are lacking many these patients. Aims: We hypothesized, from concept synthetic lethality, that asparaginase‐resistant leukemia cells harbor gain‐of‐fitness alterations could be exploited therapeutically. Methods: To identify molecular pathways promote leukemic cell fitness upon with...