A5070728825- Protein Degradation and Inhibitors
- Renal cell carcinoma treatment
- Renal and related cancers
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Coral and Marine Ecosystems Studies
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Marine Biology and Ecology Research
- Marine and coastal plant biology
- Virus-based gene therapy research
- Genetic Mapping and Diversity in Plants and Animals
- Melanoma and MAPK Pathways
- Click Chemistry and Applications
- Meat and Animal Product Quality
- Marine Ecology and Invasive Species
- Genetic diversity and population structure
- GABA and Rice Research
- Biofuel production and bioconversion
- Monoclonal and Polyclonal Antibodies Research
- Cephalopods and Marine Biology
- Marine Invertebrate Physiology and Ecology
- Bladder and Urothelial Cancer Treatments
- Plant nutrient uptake and metabolism
University of Utah
2014-2023
Huntsman Cancer Institute
2014-2023
Royal Holloway University of London
2004
Newcastle University
2002
Scottish Association For Marine Science
1997
Swansea University
1994-1997
University of Wales
1994-1997
Australian Institute of Marine Science
1994-1995
Endosperm is an absorptive structure that supports embryo development or seedling germination in angiosperms. The endosperm of cereals a main source food, feed, and industrial raw materials worldwide. However, the genetic networks regulate cell differentiation remain largely unclear. As first step toward characterizing these networks, we profiled mRNAs five major types differentiating four maternal compartments maize (Zea mays) kernel. Comparisons mRNA populations revealed diverged gene...
Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate effect activated AKT1 expression non-metastatic BRAF(V600E)/Cdkn2a(Null) mouse melanomas vivo. Expression resulted highly metastatic with lung and brain 67% 17% our mice, respectively. Silencing PTEN cooperated AKT1, resulting decreased tumor latency development nearly 80% tumor-bearing mice. These data demonstrate that activation...
Significance In flowering plants, double fertilization gives rise to an embryo and the endosperm, absorptive storage structure that supports embryogenesis seedling germination. cereal grains, endosperm comprises a large proportion of mature seed, contains amounts carbohydrates proteins, is important source food, feed, industrial raw materials. This study provides comprehensive profile genes expressed in early developing maize. We also show how series temporal programs gene expression...
Many species of echinoderms, in all five extant classes, contain subcuticular bacterial symbionts (SCB). The role these extracellular and the nature relationship remain unclear. We have sequenced 16S rRNA genes from to determine their phylogenetic affinities. Symbionts an ophiuroid, Ophiactis balli, appear closely related bacteria within alpha group class Proteobacteria, including intracellular endosymbionts pathogens. SCB are clearly separate origin other documented major groups marine...
Potential anti-inflammatory and anticarcinogenic effects of aspirin (ASA) may be suitable for melanoma chemoprevention, but defining biomarkers in relevant target tissues is prerequisite to performing randomized controlled chemoprevention trials. We conducted open-label studies with ASA 53 human subjects melanocytic nevi at increased risk melanoma. In a pilot study, 12 received single dose (325 mg) ASA; metabolites salicylate, salicylurate, gentisic acid were detected plasma after 4–8 h,...
Abstract Aberrant activation of the PI3K–AKT pathway is common in many cancers, including melanoma, and AKT1, 2 3 (AKT1–3) are bona fide oncoprotein kinases with well-validated downstream effectors. However, efforts to pharmacologically inhibit AKT have proven be largely ineffective. In this study, we observed paradoxical effects following either pharmacologic or genetic inhibition AKT1–3 melanoma cells. Although pharmacological was without effect, silencing all three paralogs significantly...
<p>Supplementary Figure S2 shows the classification of MTG001 and MTG004. Immunoblotting MTG004 PDX-derived cell lines showed similar levels P-AKT (Ser473), total AKT, P-ERK (Thr202/Tyr204), ERK1/2, P-Ribosomal S6 Kinase (Ser235/236), Kinase. GAPDH was used as a loading control. The cells exhibited higher PTEN. Analysis RNA sequencing data demonstrated that both express wildtype PTEN.</p>
<p>Supplementary Figure S1 shows that pharmacological inhibition of AKT has little effect on melanoma cells. Cell confluency assay under inhibition. A375, HT144, SK-MEL28, WM793, MTG001, and MTG004 cells were largely resistant to inhibitors MK2206 (2.5 µM) GDC0068 (1µM) while SK-MEL 28 MTG001 sensitive PI3Kα by GDC0941 (P < 0.001). Error bars indicate standard error the mean triplicate wells.</p>
<p>Supplementary Figure S2 shows the classification of MTG001 and MTG004. Immunoblotting MTG004 PDX-derived cell lines showed similar levels P-AKT (Ser473), total AKT, P-ERK (Thr202/Tyr204), ERK1/2, P-Ribosomal S6 Kinase (Ser235/236), Kinase. GAPDH was used as a loading control. The cells exhibited higher PTEN. Analysis RNA sequencing data demonstrated that both express wildtype PTEN.</p>
<p>Supplementary Figure S4 demonstrates that siAKT1-3 is specific for human AKT. A, The cell confluency assay of YUMM1.1 mouse melanoma cells under genetic inhibition demonstrated no effect on death with siAKT1, siAKT2, siAKT3, or any combination. Error bars indicate standard error the mean triplicate wells. B, Immunoblotting treated siCtrl vs siAKT1-3. No knockdown P-AKT (Ser473) P-PRAS40 (T246) indicated specificity siRNAs AKT.</p>
<p>Supplementary Figure S7 shows chemical structures of all pharmacological agents utilized in study, including MK2206, GSK2141795, GDC-0941, BYL719, RapaLink-1, GSK650394, GDC-0068, GDC-0084, and INY-03-041.</p>
<p>Supplementary Figure S3 shows confirmation of AKT expression and knockdown in additional cell lines. A, Immunoblotting analysis WM793 HT144 cells treated with each siRNA alone or combination showed effective individual paralogs using antibodies against total AKT1, AKT2, AKT3. B, Expression paralog MTG001 MTG004 RT-PCR.</p>
<p>Supplementary Figure S7 shows chemical structures of all pharmacological agents utilized in study, including MK2206, GSK2141795, GDC-0941, BYL719, RapaLink-1, GSK650394, GDC-0068, GDC-0084, and INY-03-041.</p>
<p>Supplementary Figure S6 shows that INY-03-041 leads to a substantial effect on melanoma cell proliferation but it is not as potent siAKT1-3. A, Cell confluency assay of MTG001 and MTG004 lines treated with DMSO control, GDC0068 (1µM), GDC0941 Lenalidomide or siAKT1-3 (50nM). Treatment led decreased (P < 0.0001 in each line), did lead death, similar MTG004. Lenalidomide, recruiter the E3 ubiquitin ligase Cereblon, conjugated form INY-03-041, was used negative control for...
<p>Supplementary Figure S1 shows that pharmacological inhibition of AKT has little effect on melanoma cells. Cell confluency assay under inhibition. A375, HT144, SK-MEL28, WM793, MTG001, and MTG004 cells were largely resistant to inhibitors MK2206 (2.5 µM) GDC0068 (1µM) while SK-MEL 28 MTG001 sensitive PI3Kα by GDC0941 (P < 0.001). Error bars indicate standard error the mean triplicate wells.</p>
<div>Abstract<p>Aberrant activation of the PI3K–AKT pathway is common in many cancers, including melanoma, and AKT1, 2 3 (AKT1–3) are <i>bona fide</i> oncoprotein kinases with well-validated downstream effectors. However, efforts to pharmacologically inhibit AKT have proven be largely ineffective. In this study, we observed paradoxical effects following either pharmacologic or genetic inhibition AKT1–3 melanoma cells. Although pharmacological was without effect,...
<p>Supplementary Figure S3 shows confirmation of AKT expression and knockdown in additional cell lines. A, Immunoblotting analysis WM793 HT144 cells treated with each siRNA alone or combination showed effective individual paralogs using antibodies against total AKT1, AKT2, AKT3. B, Expression paralog MTG001 MTG004 RT-PCR.</p>
<p>Supplemental Figure 5 shows that caspase 3 and 8 inhibition protects melanoma cells from siAKT1-3-mediated apoptosis. A, Cell confluency assay upon treatment with siAKT1-3 versus co-treatment inhibitors. Co-treatment of A375 MTG004 Z-VAD-FMK, Z-DEVD-FMK, Z-IETD-FMK inhibitors protected against cell death. B, Incuycte® Cytotox Red comparing siCtrl, siAKT1-3, siCtrl + each inhibitor, C, Caspase 3/7 The percentage dead stained red reagents increased only in the group, indicating...
<p>Supplementary Figure S6 shows that INY-03-041 leads to a substantial effect on melanoma cell proliferation but it is not as potent siAKT1-3. A, Cell confluency assay of MTG001 and MTG004 lines treated with DMSO control, GDC0068 (1µM), GDC0941 Lenalidomide or siAKT1-3 (50nM). Treatment led decreased (P < 0.0001 in each line), did lead death, similar MTG004. Lenalidomide, recruiter the E3 ubiquitin ligase Cereblon, conjugated form INY-03-041, was used negative control for...
<p>Supplemental Figure 5 shows that caspase 3 and 8 inhibition protects melanoma cells from siAKT1-3-mediated apoptosis. A, Cell confluency assay upon treatment with siAKT1-3 versus co-treatment inhibitors. Co-treatment of A375 MTG004 Z-VAD-FMK, Z-DEVD-FMK, Z-IETD-FMK inhibitors protected against cell death. B, Incuycte® Cytotox Red comparing siCtrl, siAKT1-3, siCtrl + each inhibitor, C, Caspase 3/7 The percentage dead stained red reagents increased only in the group, indicating...