A5042449515- Acute Myeloid Leukemia Research
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Metabolism, Diabetes, and Cancer
- HIV/AIDS drug development and treatment
- Cancer-related cognitive impairment studies
- Protein Degradation and Inhibitors
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer survivorship and care
- Pancreatic function and diabetes
- Cancer Risks and Factors
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- RNA Research and Splicing
- Hematopoietic Stem Cell Transplantation
- Autophagy in Disease and Therapy
- Chromatin Remodeling and Cancer
- Mitochondrial Function and Pathology
- Plant biochemistry and biosynthesis
- Cancer Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
- Complement system in diseases
- Liver physiology and pathology
- PARP inhibition in cancer therapy
- Plant and Fungal Interactions Research
University of Pennsylvania
2018-2025
Philadelphia University
2023
Hospital of the University of Pennsylvania
2018-2021
Inserm
2014-2020
Centre National de la Recherche Scientifique
2020
Centre de Recherche en Cancérologie de Toulouse
2013-2020
Johns Hopkins University
2016-2018
Johns Hopkins Medicine
2016-2018
Université Toulouse III - Paul Sabatier
2013
High-grade gliomas, glioblastomas (GB), are refractory to conventional treatment combining surgery, chemotherapy, mainly temozolomide, and radiotherapy. This highlights an urgent need develop novel therapies increase the efficacy of radio/chemotherapy for these very aggressive malignant brain tumors. Recently, tumor metabolism became interesting potential therapeutic target in various cancers. Accordingly, drugs targeting cell with appropriate chemotherapeutic agents or radiotherapy has...
Abstract Autophagy has been associated with oncogenesis one of its emerging key functions being contribution to the metabolism tumors. Therefore, deciphering mechanisms how autophagy supports tumor cell is essential. Here, we demonstrate that inhibition induces an accumulation lipid droplets (LD) due a decrease in fatty acid β-oxidation, leads reduction oxidative phosphorylation (OxPHOS) acute myeloid leukemia (AML), but not normal cells. Thus, autophagic process participates catabolism...
Abstract Intensive chemotherapy with cytarabine and anthracycline (7&3) remains the standard therapy for patients medically fit induction, but assessment of fitness controversial. Venetoclax hypomethylating agent (ven/HMA) combination has improved outcomes in unfit no prospective study assessed ven/HMA versus 7&3 as initial older, patients. Given studies expectation use outside trial criteria, we evaluated retrospective among newly diagnosed A nationwide electronic health record...
Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts splicing of mitochondrial mRNAs, impairs complex I function, robustly increases mitophagy. also identified a surveillance mechanism by which dysfunction modifies mitophagy activator PINK1 to remove poison intron, increasing stability abundance mRNA protein. SRSF2P95H-induced...
Mutations and deletions in TP53 are associated with adverse outcomes patients myeloid malignancies developing improved therapies for TP53-mutant leukemias is of urgent need. Here we identify mutations TET2 as the most common co-occurring mutation mutant acute leukemia (AML) patients. In mice, combined hematopoietic-specific deletion resulted enhanced self-renewal compared to either gene alone. Tp53/Tet2 double knockout mice developed serially transplantable AML. Both AML TET2/TP53...
Abstract Xenotransplantation of acute myeloid leukemia (AML) cells is an established model for preclinical development and understanding AML biology. xenotransplantation has been well characterized in highly immunocompromised NSG mice, but time to engraftment this strain often prolonged some types engraft poorly. In particular, we have found that TP53 mutant splicing factor poorly mice. Alternative mouse models are NSG-SGM3 (SGM3) NOG-EXL which combine severe immunodeficiency with transgenic...
Glioblastomas (GBM) are very aggressive and malignant brain tumors, with frequent relapses despite an appropriate treatment combining surgery, chemotherapy radiotherapy. In GBM, hypoxia is a characteristic feature activation of Hypoxia Inducible Factors (HIF-1α HIF-2α) has been associated resistance to anti-cancer therapeutics. Int6, also named eIF3e, the “e” subunit translation initiation factor eIF3, was identified as novel regulator HIF-2α. Eukaryotic factors (eIFs) key regulating total...
// Joshua Casaos 1 , Sakibul Huq Tarik Lott Raphael Felder John Choi Noah Gorelick Michael Peters Yuanxuan Xia Russell Maxwell Tianna Zhao Chenchen Ji Thomas Simon 2 Julie Sesen 1, 3 Sarah J. Scotland Richard E. Kast 4 Jeffrey Rubens 5 Eric Raabe Charles G. Eberhart M. Jackson Henry Brem Betty Tyler * and Nicolas Skuli 3, Hunterian Neurosurgical Research Laboratory, Neurosurgery Department, Johns Hopkins School of Medicine, University, Baltimore, MD 21231, USA Center for Vascular...
Abstract Acute myeloid leukemia (AML) with mutations in the tumor suppressor gene, TP53 ( mut AML), is fatal a median survival of only 6 months. RNA sequencing on purified AML patient samples show has higher expression mevalonate pathway genes. We retrospectively identified benefit patients who received chemotherapy concurrently statin, which inhibits pathway. Mechanistically, resistance to standard chemotherapy, cytarabine (AraC), correlates increased activity and mitochondria stress...
Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic