A5037979147- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- Advanced Breast Cancer Therapies
- Histone Deacetylase Inhibitors Research
- Cancer Immunotherapy and Biomarkers
- Chronic Myeloid Leukemia Treatments
- Neuroendocrine Tumor Research Advances
- Ubiquitin and proteasome pathways
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Multiple Myeloma Research and Treatments
- RNA modifications and cancer
- Cancer Research and Treatments
- DNA and Nucleic Acid Chemistry
- Immune cells in cancer
- Advanced biosensing and bioanalysis techniques
University of Utah
2011-2025
Io Therapeutics (United States)
2024
Tolero Pharmaceuticals (United States)
2012-2021
Sumitomo Dainippon Pharma (United States)
2020-2021
The University of Texas MD Anderson Cancer Center
2012-2019
Huntsman Cancer Institute
2010-2018
Brigham Young University
1995-2014
SuperGen (United States)
2007-2013
Astex Pharmaceuticals
2012-2013
China Medical University
2013
The nuclease hypersensitivity element III 1 upstream of the P1 promoter c- MYC controls 85–90% transcriptional activation this gene. We have demonstrated that purine-rich strand DNA in region can form two different intramolecular G-quadruplex structures, only one which seems to be biologically relevant. This relevant structure is kinetically favored chair-form G-quadruplex, destabilized when mutated with a single G → A transition, resulting 3-fold increase basal activity promoter. cationic...
Epithelial-mesenchymal transition (EMT) has been associated with metastatic spread and EGF receptor (EGFR) inhibitor resistance. We developed validated a robust 76-gene EMT signature using gene expression profiles from four platforms non-small cell lung carcinoma (NSCLC) lines patients treated in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) study.We conducted an integrated expression, proteomic, drug response analysis tumors NSCLC. A was...
YY1 is a mammalian zinc-finger transcription factor with unusual structural and functional features. It has been implicated as positive negative regulatory that binds to the CCATNTT consensus DNA element located in promoters of many cellular viral genes. A cDNA encodes YY1-binding protein possesses sequence homology yeast transcriptional RPD3 identified. Gal4 binding domain–mammalian fusion strongly represses from promoter containing sites. Association between requires glycine-rich region on...
<i>Neu</i> (c-<i>erbB2</i>) is a proto-oncogene product that encodes an epidermal growth factor-like receptor tyrosine kinase. Amplification of wild-type c-<i>Neu</i>and mutational activation (<i>Neu T</i>) have been implicated in oncogenic transformation cultured fibroblasts and mammary tumorigenesis <i>in vivo</i>. Here, we examine the relationship between Neu kinase activity caveolin-1 protein expression vitro</i> vivo.</i> Recent studies suggested caveolins may function as negative...
Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on H3 is attractive therapeutic target multiple malignancies. Here we report a structure-based virtual screen of compound library containing ∼2 million small molecular entities. Computational docking scoring followed by biochemical screening led to the identification novel N'-(1-phenylethylidene)-benzohydrazide series LSD1 inhibitors with hits showing IC50s 200-400 nM...
Abstract Methylation of CpG islands in promoter regions is often associated with gene silencing and aberrant DNA methylation occurs most cancers, leading to the some tumor suppressor genes. Reversal this abnormal hypermethylation by inhibitors effective reactivating methylation-silenced genes both vitro vivo. Several have been well studied; potent among them 5-aza-2′-deoxycytidine (5-Aza-CdR), which can induce myelosuppression patients. S110 a dinucleotide consisting 5-Aza-CdR followed...
The farnesyltransferase inhibitor L-744,832 selectively blocks the transformed phenotype of cultured cells expressing a mutated H-ras gene and induces dramatic regression mammary salivary carcinomas in mouse tumor virus (MMTV)-v-Ha-ras transgenic mice. To better understand how inhibitors might be used treatment human tumors, we have further explored mechanisms by which variety models. We assessed whether apoptosis or alterations cell cycle distribution found that MMTV-v-Ha-ras mice could...
The serine/threonine family of Pim kinases function as oncogenes and have been implicated in prostate cancer progression, particularly hormone-refractory disease, a result their antiapoptotic function. In this study, we used pharmacologic inhibitor targeting the members, SGI-1776, to determine whether modulation kinase activity could alter cell survival modulate chemotherapy resistance. Extensive biochemical characterization SGI-1776 confirmed its specificity for three isoforms family....
The receptor tyrosine kinase AXL has emerged in recent years as an potential oncology target due to its over expression several types of cancers coupled with ability promote tumor growth and metastasis. In order identify small molecule inhibitors AXL, we built a homology model catalytic domain virtually screen scaffolds displaying affinity for AXL. Further computational structure-based design resulted the synthesis series 2,4,5-trisubstitued pyrimidines which demonstrated potent inhibition...
The proto-oncogene proviral integration site for moloney murine leukemia virus (PIM) kinases (PIM-1, PIM-2, and PIM-3) are serine/threonine that involved in a number of signaling pathways important to cancer cells. PIM act downstream effector functions as inhibitors apoptosis positive regulators G1-S phase progression through the cell cycle. upregulated multiple indications, including lymphoma, leukemia, myeloma, prostate, gastric, head neck cancers. Overexpression one or more family members...
Inflammatory breast cancer (IBC) is the most lethal form of cancer, but basis for its aggressive properties are not fully understood. In this study, we report that high tumoral expression TIG1 (RARRES1), a functionally undefined membrane protein, confers shorter survival in patients with IBC. depletion decreased IBC cell proliferation, migration, and invasion vitro inhibited tumor growth cells vivo. We identified receptor tyrosine kinase, Axl, as TIG1-binding protein. interaction stablilized...
More effective treatment options for elderly acute myeloid leukemia (AML) patients are needed as only 25-50% of respond to standard-of-care therapies, response duration is typically short, and disease progression inevitable even with some novel therapies ongoing clinical trials. Anti-apoptotic BCL-2 family inhibitors, such venetoclax, promising AML. Nonetheless, resistance emerging. We demonstrate that venetoclax combined cyclin-dependent kinase (CDK) inhibitor alvocidib potently synergistic...
B-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL survival. Here, we explored the possibility of using high-affinity inhibitor as single agent or combination with Bruton's (BTK) inhibitors for future clinical trial to treat patients CLL.Expression/activation status other members TAM (e.g., Tyro3, Axl, and MER) family RTKs B cells was evaluated....
Cytometry by time-of-flight (CyTOF) simultaneously measures multiple cellular proteins at the single-cell level and is used to assess intertumor intratumor heterogeneity. This approach may be investigate variability of individual tumor responses treatments. Herein, we stratified lung subpopulations based on AXL signaling as a potential targeting strategy. Integrative transcriptome analyses were how TP-0903, an kinase inhibitor, influences redundant oncogenic pathways in metastatic cancer...