A5046066554- Autophagy in Disease and Therapy
- Cancer Genomics and Diagnostics
- Ferroptosis and cancer prognosis
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- Endoplasmic Reticulum Stress and Disease
- Cell death mechanisms and regulation
- Phagocytosis and Immune Regulation
- Synthesis and biological activity
- Cancer Mechanisms and Therapy
- Inflammasome and immune disorders
- RNA modifications and cancer
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Synthesis and Characterization of Heterocyclic Compounds
- interferon and immune responses
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Protein Degradation and Inhibitors
- Sphingolipid Metabolism and Signaling
- Environmental Impact and Sustainability
Stanford University
2020-2025
University of California, San Francisco
2025
University of Chicago
2019-2023
Abstract The impact of clonal heterogeneity on disease behavior or drug response in acute myeloid leukemia remains poorly understood. Using a cohort 2,829 patients, we identify features clonality associated with clinical and sensitivities. High variant allele frequency for 7 mutations (including NRAS TET2 ) associate dismal prognosis; elevated GATA2 correlates better outcomes. Clinical such as white blood cell count blast percentage correlate the subclonal abundance TP53 IDH1 . Furthermore,...
Small molecules that induce non-apoptotic cell death are of fundamental mechanistic interest and may be useful to treat certain cancers. Here, we report tegavivint, a drug candidate undergoing human clinical trials, can activate unique mechanism in sarcomas other cancer cells. This lethal is distinct from ferroptosis, necroptosis pyroptosis requires the lipid metabolic enzyme trans -2,3-enoyl-CoA reductase (TECR). TECR canonically involved synthesis very long chain fatty acids but appears...
Therapy resistance is a significant cause of death in patients treated with targeted cancer therapy diverse oncogene-driven cancers. A better understanding mechanisms can lay the foundation for improving existing and developing new therapies. recent elegant study published Nature Chemical Biology sheds light on mechanism. The authors define novel role ARAF, member RAF protein family (A-, B-, C-RAF), that distinct from its previously understood as RAS effector MEK kinase MAPK pathway. They...
Mammalian cells can die by apoptosis or one of several non-apoptotic mechanisms, such as ferroptosis. Here, we present a protocol to distinguish ferroptosis from other cell death mechanisms in cultured cells. We describe steps for seeding cells, administering mechanism-specific inducers and inhibitors, measuring viability. then detail the use molecular markers verify death. This be used identify 2D 3D cultures. For complete details on execution this protocol, please refer Ko, et al. (2019),
Diffuse large B-cell lymphoma (DLBCL) remains a formidable diagnosis in need of new treatment paradigms. In this work, we elucidated an opportunity for therapeutic synergy DLBCL by reactivating tumor protein p53 with stapled peptide, ATSP-7041, thereby priming cells apoptosis and enhancing their sensitivity to BCL-2 family modulation BH3-mimetic, ABT-263 (navitoclax). While combination was highly effective at activating vitro, it toxic vivo, resulting prohibitively narrow window. We,...
// Abbas Hadji 1 , Greta K. Schmitt Mathew R. Schnorenberg 2 Lauren Roach Connie M. Hickey Logan B. Leak Matthew V. Tirrell and James L. LaBelle Department of Pediatrics, Section Hematology/Oncology/Stem Cell Transplantation Committee on Cancer Biology, University Chicago, IL 60637, USA Pritzker School Molecular Engineering, Correspondence to: LaBelle, email: jlabelle@peds.bsd.uchicago.edu Keywords: MCL-1; BIM; BH3 mimetic; stapled peptides; apoptosis Received: February 08, 2019 Accepted:...
Apoptosis is the most well-studied form of cell death, but there exist other death pathways that also have roles in normal physiology and disease. It unclear what forms remain to be discovered how these could inform our understanding molecular biology. Caspase-independent lethal 56 (CIL56) a compound kills cells via novel mechanism. We conducted genome-wide CRISPR screen identify regulators this pathway. From screen, we identified trans-2-enoyl-CoA reductase (TECR) as key regulator...