A5002765913- PI3K/AKT/mTOR signaling in cancer
- Hops Chemistry and Applications
- Cancer Mechanisms and Therapy
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related gene regulation
- Neuroblastoma Research and Treatments
- Cancer-related molecular mechanisms research
- DNA Repair Mechanisms
- Neuroendocrine Tumor Research Advances
- Bacterial Genetics and Biotechnology
- Liver physiology and pathology
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Kruppel-like factors research
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Microtubule and mitosis dynamics
- Connective Tissue Growth Factor Research
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Garlic and Onion Studies
BioVentures (United States)
2023-2024
The University of Texas MD Anderson Cancer Center
2020-2023
The University of Texas Health Science Center at Houston
2020
Medical College of Wisconsin
2014-2019
Medical College of Wisconsin Cancer Center
2015
Madison Group (United States)
2014
University of Wisconsin–Madison
2004-2012
University of Wisconsin Carbone Cancer Center
2012
Abstract RAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog define separable replication stability roles informed by its three-dimensional structure, assembly, unappreciated polymerization motif. Mapping of cancer...
Despite improvement in therapeutic strategies, median survival advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects various cancers types vitro. XN treatment healthy mice and humans yielded favorable pharmacokinetics bioavailability. we determined study the of understand mechanism its action HCC. The on panel HCC...
Pancreatic cancer remains a lethal disease with limited treatment options. At the time of diagnosis, approximately 80% these patients present unresectable tumors caused by either locally advanced lesions or progressive metastatic growth. Therefore, development novel strategies and new therapeutics is needed. Xanthohumol (XN) has emerged as potential compound that inhibits various types cancer, but molecular mechanism underlying effects XN unclear. In study, we have assessed efficacy on...
Mitochondrial DNA (mtDNA) instability activates cGAS-dependent innate immune signaling by unknown mechanisms. Here, we find that Fanconi anemia suppressor genes are acting in the mitochondria to protect mtDNA replication forks from instability. Specifically, patient cells show a loss of nascent through MRE11 nuclease degradation. In contrast fork stability, which requires pathway activation FANCD2-FANCI monoubiquitination and upstream FANC core complex genes, mitochondrial protection does...
Neuroblastoma (NB) is a devastating disease. Despite recent advances in the treatment of NB, about 60% high-risk NB will have relapse and therefore long-term event free survival very minimal. We reported that targeting glycogen synthase kinase-3 (GSK-3) may be potential strategy to treat NB. Consequently, investigating LY2090314, clinically relevant GSK-3 inhibitor, on cellular proliferation beneficial for treatment.The effect LY2090314 was compared with previously studied Tideglusib....
Objective: Neuroblastoma is a common neuroendocrine (NE) tumor that presents in early childhood, with high incidence of malignancy and recurrence. The glycogen synthase kinase-3 (GSK-3) pathway potential therapeutic target, as this has been shown to be crucial the management other NE tumors. However, it not known which isoform necessary for growth inhibition. In study, we investigated effect GSK-3 inhibitor AR-A014418 on different isoforms neuroblastoma. Methods: NGP SH-5Y-SY cells were...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Mito-carboxy proxyl (Mito-CP), a lipophilic cationic nitroxide, accumulates in mitochondria because large negative transmembrane potential. Studies have shown that these agents act by disrupting energy-producing mechanism, inducing mitochondrial-mediated apoptosis, and also enhancing action other chemotherapeutic cancer cells. We hypothesized combination Mito-CP glycolysis inhibitor, 2-deoxyglucose...
Cholangiocarcinoma (CCA) is an aggressive disease with limited effective treatment options. The PI3K/Akt/mTOR pathway represents attractive therapeutic target due to its frequent dysregulation in CCA. MK2206, allosteric Akt inhibitor, has been shown reduce cellular proliferation other cancers. We hypothesized that MK2206 mediated inhibition of would impact CCA viability.Post (0-2 μM), viability was assessed two human cell lines-CCLP-1 and SG231-using MTT assay. Lysates from the treated cells...
Cholangiocarcinoma remains the second most prevalent hepatic neoplasm in United States with a 5-year survival rate of less than 10%. Currently, no systemic therapy has demonstrated efficacy. Therefore, an urgent need for identification molecularly targeted compound(s) remains. The Notch signaling pathway been shown to be dysregulated cholangiocarcinoma, exhibiting hyperactivity while also possibly mediating chemotherapeutic resistance. We analyzed effects xanthohumol, prenylated chalcone, on...
Abstract The TEAD transcription factors in association with the YAP/TAZ co-activators drive expression of pro-proliferative and pro-oncogenic genes that underlies transformed phenotype many carcinomas. In addition, YAP-TEAD transcriptional activity is emerging as a major resistance mechanism for diverse precision oncology drugs, most extensive data to drugs targeting MAPK pathway. There strong interest generating inhibitors YAP/TEAD palmitic acid site having demonstrated encouraging...
High-risk neuroblastoma (NB) is lethal childhood cancer. Published data including ours have reported the anti-proliferative effect of Xanthohumol (XN), a prenylated chalcone, in various cancer types suggesting that XN could be useful small molecule compound against The TNF-Related Apoptosis-Inducing Ligand (TRAIL) an endogenous ligand expressed immune cells. TRAIL mediates apoptosis through binding transmembrane receptors, death receptor 4 (DR4) and/or 5 (DR5). Cancer cells are frequently...
Carcinoids are neuroendocrine malignancies characterized by their overproduction of various bioactive hormones that lead to the carcinoid syndrome. We have shown previously AKT serves as a key regulator growth and phenotypic expression tumor markers in carcinoids genetic depletion expression. However, no small-molecule inhibitor kinase activity has been developed until recently. MK-2206, novel allosteric AKT, is currently undergoing clinical trials for treatment solid tumors. In this study,...
One proposed mechanism of replication inhibition in iteron-containing plasmids (ICPs) is "handcuffing," which the coupling origins via iteron-bound initiator (Rep) protein turns off origin function. In minimal R6K replicons, copy number control requires interaction plasmid-encoded pi with seven 22-bp iterons gamma replication. Like other related Rep proteins, exists as both monomers and dimers. However, ability dimers to bind distinguishes from most ICPs, where only have been observed...
The use of alternative therapeutic approaches in advanced carcinogenesis is a growing investigative base. One such cancer, primary liver one the most commonly occurring cancers worldwide and often presents late stage disease consequently preventing traditional curative modalities. As result, hepatocellular carcinoma (HCC), representing majority third common cause cancer-related deaths globally. Survival rates are linked to presentation as well concomitant cirrhosis limiting 5-year survival...
Discerning the interactions between initiator protein and origin of replication should provide insights into mechanism DNA initiation. In γ plasmid R6K, Rep protein, π, is distinctive in that it can bind seven 22-bp iterons two forms; π monomers activate replication, whereas dimers act as inhibitors. this work, we used wild type variants with altered monomer/dimer ratios to study iteron/π interactions. High resolution contact mapping was conducted using multiple techniques (missing base...
Abstract The Hippo pathway is an important regulator of cell proliferation and one the last major oncogenic pathways not yet extensively targeted in precision oncology. executed by YAP1/TAZ (WWTR1) co-activators TEAD family transcription factors, which consists four paralogs (TEAD1-4) with both redundant unique functions. transcriptional targets TEADs include genes playing tumor-promoting roles, including pro-proliferative, immunosuppressive, anti-apoptotic genes. A growing body research...
In previous work, we characterized the bases in an iteron of plasmid R6K that are important for binding pi protein monomers and dimers. Here investigate following six amino acids pi, encoded by pir, hypothesized to be DNA contact: Ser71, Try74, Gly131, Gly211, Arg225, Arg254.
Abstract The Hippo pathway, a critical cell proliferation regulator, remains an underexplored oncogenic pathway in precision oncology. It is executed through YAP1/TAZ co-activators and the TEAD transcription factor family (TEAD1-4), driving expression of tumor-promoting genes. Palmitic acid site inhibitors have shown strong pre-clinical clinical activity, but identification genetic markers vulnerability patient selection remain urgent open question. Sporos undertook broad bioinformatic...