A5008141260- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Acute Lymphoblastic Leukemia research
- Chronic Myeloid Leukemia Treatments
- Protein Tyrosine Phosphatases
- Genetics and Neurodevelopmental Disorders
- Hemoglobinopathies and Related Disorders
- Chromosomal and Genetic Variations
- Dermatology and Skin Diseases
- Biochemical and Molecular Research
- Microtubule and mitosis dynamics
- Connective Tissue Growth Factor Research
- HIV/AIDS drug development and treatment
- IL-33, ST2, and ILC Pathways
- Microbial Natural Products and Biosynthesis
- Biomarkers in Disease Mechanisms
- Animal Behavior and Welfare Studies
- RNA Interference and Gene Delivery
University of Michigan
2014-2023
Michigan Medicine
2021
University of Chicago
2005-2007
University of Illinois Chicago
2002-2006
University of California, San Diego
2006
Children's Hospital of Philadelphia
2006
May Institute
2005-2006
CYR61 (CCN1) is a member of the CCN family secreted matricellular proteins that includes connective tissue growth factor (CCN2), NOV (CCN3), WISP-1 (CCN4), WISP-2 (CCN5), and WISP-3 (CCN6). First identified as product factor-inducible immediate-early gene, an extracellular matrix-associated angiogenic inducer functions ligand integrin receptors to promote cell adhesion, migration, proliferation. Aberrant expression Cyr61 associated with breast cancer, wound healing, vascular diseases such...
Chromosomal translocations involving the mixed lineage leukemia (MLL) gene lead to development of acute leukemias. Constitutive HOX activation by MLL fusion proteins is required for MLL-mediated leukemogenesis; however, underlying mechanisms remain elusive. Here, we show that chromobox homolog 8 (CBX8), a Polycomb Group protein interacts with MLL-AF9 and TIP60, MLL-AF9-induced transcriptional leukemogenesis. Conversely, both CBX8 ablation specific disruption interaction point mutations in...
Abstract Overexpression of EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. has been mainly studied as the catalytic component Polycomb Repressive Complex 2 (PRC2) that mediates gene repression by trimethylating histone H3 at lysine 27 (H3K27me3). However, how drives metastasis despite low H3K27me3 levels observed ER- is unknown. Here we show human invasive carcinomas and distant metastases, cytoplasmic phosphorylated T367 significantly associated with disease...
Significance Acute myeloid leukemia (AML) is a highly heterogeneous form of cancer that results from the uncontrolled proliferation primitive immune cells. Homeobox A9 (HOXA9) an evolutionarily conserved transcription factor overexpressed in large percentage AML cases and associated with poor prognosis. Here, we show CCAAT/enhancer binding protein alpha (C/EBPα), involved cell development commonly mutated AML, critical collaborator required for HOXA9-mediated leukemic transformation. We also...
Thrombocytosis is associated with inflammation, and certain inflammatory cytokines, including IFN-γ, stimulate megakaryocyte platelet production. However, the roles of IFN-γ its downstream effector STAT1 in development are poorly understood. We previously reported that expression was significantly downregulated Gata1-knockdown murine megakaryocytes, which also have impaired terminal maturation. Here, we show ectopic STAT1, or target IRF-1, rescued multiple defects Gata1-deficient...
Abstract ASH1L histone methyltransferase plays a crucial role in the pathogenesis of different diseases, including acute leukemia. While represents an attractive drug target, developing inhibitors is challenging, as catalytic SET domain adapts inactive conformation with autoinhibitory loop blocking access to active site. Here, by applying fragment-based screening followed medicinal chemistry and structure-based design, we developed first-in-class small molecule domain. The crystal structures...
Epigenetic regulators play a critical role in normal and malignant hematopoiesis. Deregulation, including epigenetic deregulation, of the HOXA gene cluster drives transformation about 50% acute myeloid leukemia. We recently showed that Histone 3 Lysine 9 methyltransferase SETDB1 negatively regulates expression pro-leukemic genes Hoxa9 its cofactor Meis1 through deposition promoter H3K9 trimethylation MLL-AF9 leukemia cells. Here, we investigated biological impact altered changes methylation...
// James Ropa 1, 2 , Nirmalya Saha 1 Zhiling Chen Justin Serio Wei Dattatreya Mellacheruvu Lili Zhao 3 Venkatesha Basrur Alexey I. Nesvizhskii and Andrew G. Muntean Department of Pathology The University Michigan Medical School, Ann Arbor, Michigan, USA Computational Medicine Bioinformatics, Biostatistics, School Public Health, Correspondence to: Muntean, email: andrewmu@umich.edu Keywords: polymerase associated factor complex; H3K9 methyltransferase; protein-protein interaction;...
MLL rearrangements occur in myeloid and lymphoid leukemias are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute leukemia (AML) mice using various proteins (MLL-FPs) observed significantly different survival outcomes. To better understand differences between these leukemias, we examined genome wide expression profiles of leukemic cells transformed MLL-FPs. RNA-sequencing pathway analysis identified c-Myc transcriptional program...