A5087651973- Cancer, Hypoxia, and Metabolism
- Enzyme function and inhibition
- Ubiquitin and proteasome pathways
- Quinazolinone synthesis and applications
- Cancer Mechanisms and Therapy
- Mitochondrial Function and Pathology
- Hippo pathway signaling and YAP/TAZ
- Pancreatic function and diabetes
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Genetics, Aging, and Longevity in Model Organisms
- Plant biochemistry and biosynthesis
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Metabolism, Diabetes, and Cancer
- Wnt/β-catenin signaling in development and cancer
- Chemical Synthesis and Analysis
- Cancer, Lipids, and Metabolism
- Liver physiology and pathology
- RNA modifications and cancer
- Gene expression and cancer classification
- Food Quality and Safety Studies
- Microbial Natural Products and Biosynthesis
- Chronic Lymphocytic Leukemia Research
Children's Hospital of Pittsburgh
2016-2025
Southwest Forestry University
2023-2025
University of Pittsburgh Medical Center
2015-2022
Weatherford College
2022
University of Pittsburgh
2015
Children's Oncology Group
2015
Jiangsu Ocean University
2007
Shanghai Ocean University
2005-2006
Abstract Compounds that selectively prevent or disrupt the association between c-Myc oncoprotein and its obligate heterodimeric partner Max (Myc-Max compounds) have been identified previously by high-throughput screening of chemical libraries. Although these agents specifically inhibit growth c-Myc–expressing cells, their clinical applicability is limited low potency. We describe here several modifications one original compounds, 10058-F4, which result in significant improvements efficacy....
The rational design of inhibitors the bHLH-ZIP oncoprotein c-Myc is hampered by a lack structure in its monomeric state. We describe herein novel, low-molecular-weight, synthetic α-helix mimetics that recognize helical transcriptionally active coiled-coil association with obligate partner Max. These compounds perturb heterodimer's binding to canonical E-box DNA sequence without causing protein–protein dissociation, heralding new mechanistic class "direct" inhibitors. In addition...
MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction maintenance. Although Myc+/- mice are healthier longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe chronic consequences body-wide inactivation initiated postnatally. "MycKO" acquire numerous features premature aging, including altered body composition habitus, metabolic dysfunction, hepatic steatosis, gene...
// Huabo Wang 1 , Peter Teriete 2 Angela Hu Dhanya Raveendra-Panickar Kelsey Pendelton John S. Lazo 3 Julie Eiseman 4,5 Toril Holien 6 Kristine Misund Ganna Oliynyk 7 Marie Arsenian-Henriksson Nicholas D. P. Cosford Anders Sundan and Edward V. Prochownik 1,5,8 Section of Hematology/Oncology, Children’s Hospital Pittsburgh UPMC, The University Medical Center, Pittsburgh, PA, USA Cell Death Survival Networks Research Program, Sanford Burnham Prebys Discovery Institute, La Jolla, CA,...
Wintersweet (Chimonanthus praecox) is known for its flowering in winter and rich floral aroma, it’s the whole flower yellow or inner petals are red. In this study, we choose wintersweet genotypes HLT040 HLT015 (belonging to C. praecox 'Luteus' group 'Grandiflorus' group, respectively) as re-search materials, studied co-regulatory mechanism of color fragrance through metabolomics transcriptomics. This study found that there were more flavonoids HLT015, anthocyanins...
Wintersweet (Chimonanthus praecox) is known for its flowering in winter and rich floral aroma; the whole flower yellow inner petals are red. In this study, we chose wintersweet genotypes HLT040 HLT015 as research materials, studied co-regulatory mechanism of color fragrance through metabolomics transcriptomics. This study found that there were more flavonoids HLT015, anthocyanins (cyanidin-3-O-rutinoside cyanidin-3-O-glucoside) only present but contained monoterpenes FVBPs (phenylpropanoid...
// Huabo Wang 1 , Jay Chauhan 2 Angela Hu Kelsey Pendleton Jeremy L. Yap Philip E. Sabato 3 Jace W. Jones Mariarita Perri 4 Jianshi Yu Erika Cione Maureen A. Kane 2,5 Steven Fletcher and Edward V. Prochownik 1,6,7 Section of Hematology/Oncology, Children's Hospital Pittsburgh UPMC Department Pharmaceutical Sciences, University Maryland School Pharmacy, Baltimore, MD, USA PharmD Program, Pharmaco-Biology, Calabria, Rende (CS), Italy 5 Marlene Stewart Greenebaum Cancer Center, 6 Microbiology...
Background & AimsThe c-Myc (Myc) Basic helix-loop-helix leucine zipper (bHLH-ZIP) transcription factor is deregulated in most cancers. In association with Max, Myc controls target genes that supervise metabolism, ribosome biogenesis, translation, and proliferation. This network crosstalks the Mlx network, which consists of Myc-like proteins MondoA ChREBP, Max-like Mlx. Together, this extended regulates both common distinct gene targets. Here, we studied consequence and/or ablation liver,...
Abstract c‐Myc is a basic helix‐loop‐helix‐leucine zipper (bHLH‐ZIP) transcription factor that responsible for the of wide range target genes involved in many cancer‐related cellular processes. Over‐expression has been observed in, and directly contributes to, variety human cancers including those hematopoietic system, lung, prostate colon. To become transcriptionally active, must first dimerize with Myc‐associated X (Max) via its own bHLH‐ZIP domain. A proven strategy towards inhibition...
// Huabo Wang 1 , Lokendra Sharma Jie Lu Paul Finch Steven Fletcher 2,3 and Edward V. Prochownik 1,4,5 Division of Hematology/Oncology, Children’s Hospital Pittsburgh University Medical Center, PA, USA 2 Department Pharmaceutical Sciences, The Maryland School Pharmacy, Baltimore, MD, 3 Greenebaum Cancer Baltimore 4 Microbiology Molecular Genetics, Pittsburgh, 5 Institute, Correspondence to: Prochownik, email: Keywords : 10058-F4, 10074-G5, JQ1, artemisinin, glycolysis Received March...
Rapidly proliferating cells increase glycolysis at the expense of oxidative phosphorylation (oxphos) to generate sufficient levels glycolytic intermediates for use as anabolic substrates. The pyruvate dehydrogenase complex (PDC) is a critical mitochondrial enzyme that catalyzes pyruvate's conversion acetyl coenzyme A (AcCoA), thereby connecting these two pathways in response energetic, enzymatic, and metabolic cues. Here we utilized mouse model hepatocyte-specific PDC inactivation determine...
Ribosomopathies comprise a heterogeneous group of hematologic and developmental disorders, often characterized by bone marrow failure, skeletal other abnormalities cancer predisposition. They are associated with mutations and/or haplo-insufficiencies ribosomal proteins (RPs) inefficient RNA (rRNA) processing. The resulting stress induces the canonical p19ARF/Mdm2/p53 tumor suppressor pathway leading to proliferative arrest apoptosis. It has been proposed that this is then inactivated during...
The c-Myc (Myc) oncoprotein and AMP-activated protein kinase (AMPK) regulate glycolysis oxidative phosphorylation (Oxphos) although often for different purposes. Because Myc over-expression depletes ATP with the resultant activation of AMPK, we explored potential co-dependency cross-talk between these proteins by comparing consequences acute induction in ampk+/+ (WT) ampk-/- (KO) murine embryo fibroblasts (MEFs). KO MEFs showed a higher basal rate than WT an appropriate increase response to...
Hepatoblastoma (HB), the most common pediatric liver cancer, often bears β-catenin mutations and deregulates Hippo tumor suppressor pathway. Murine HBs can be generated by co-expressing mutants constitutively active effector YAPS127A. Some other cancers also express of NFE2L2/NRF2 (NFE2L2), a transcription factor that tempers oxidative electrophilic stress. In doing so, NFE2L2 either suppresses or facilitates tumorigenesis.We evaluated NFE2L2's role in HB pathogenesis all combinations mutant...
In two different mouse liver cancer models, we recently showed that a switch from oxidative phosphorylation (Oxphos) to glycolysis (the Warburg effect) is invariably accompanied by marked decline in fatty acid oxidation (FAO) and reciprocal increase the activity of pyruvate dehydrogenase (PDH), which links TCA cycle. We now show short-term implementation either medium-chain (MC) or long-chain (LC) high fat diets (HFDs) nearly doubled survival mice with c-Myc oncoprotein-driven hepatocellular...