A5021352996- Prostate Cancer Treatment and Research
- Cell death mechanisms and regulation
- Estrogen and related hormone effects
- DNA Repair Mechanisms
- Advanced Proteomics Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Autophagy in Disease and Therapy
- MicroRNA in disease regulation
- Steroid Chemistry and Biochemistry
- Mass Spectrometry Techniques and Applications
- FOXO transcription factor regulation
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Polyomavirus and related diseases
- Trace Elements in Health
- Microtubule and mitosis dynamics
- Pancreatic and Hepatic Oncology Research
- Genetics, Aging, and Longevity in Model Organisms
- ATP Synthase and ATPases Research
New York University
2018-2023
Centre for Cancer Biology
2012-2016
University of South Australia
2014-2016
South Australia Pathology
2012-2013
The University of Adelaide
2012-2013
A hallmark of pancreatic tumors is their highly desmoplastic stroma composed fibroblasts, immune cells, and a dense network collagen fibers. Tumor-associated macrophages are one the most abundant cell populations in tumor stroma. Their protumorigenic function has been attributed predominantly to capacity promote evasion metastasis. Tumor-assoc iated also well known for role remodeling via production degradation, with latter being mediated by mannose receptor (MRC1)-dependent endocytosis...
Caspase-2, one of the most evolutionarily conserved caspase family, has been implicated in maintenance chromosomal stability and tumour suppression. Caspase-2 deficient (Casp2−/−) mice develop normally but show premature ageing-related traits when challenged by certain stressors, succumb to enhanced development aneuploidy. To test how caspase-2 protects against instability, we utilized an ex vivo system for aneuploidy where primary splenocytes from Casp2−/− were exposed anti-mitotic drugs...
Significance The cysteine protease caspase-2 has been implicated in the suppression of oncogene-mediated tumor formation. However, mechanisms underlying function as a suppressor are not well defined. In this study, we use well-characterized mouse lymphoma model and demonstrate critical role for maintaining genome stability tumorigenesis following loss essential DNA repair gene ataxia telangiectasia mutated ( Atm ). Our findings suggest that cooperates with ATM to suppress genomic...
Ageing is a complex biological process for which underlying biochemical changes are still largely unknown. We performed comparative profiling of the cellular proteome and metabolome to understand molecular basis ageing in Caspase-2-deficient (Casp2(-/-)) mice that model premature absence overt disease. Age-related were determined liver serum young (6-9 week) aged (18-24 month) wild-type Casp2(-/-) mice. identified perturbed metabolic pathways, decreased levels ribosomal respiratory proteins...
Aberrant cell death/survival has a critical role in the development of hepatocellular carcinoma (HCC). Caspase-2, death protease, limits oxidative stress and chromosomal instability. To study its reactive oxygen species (ROS) DNA damage-induced liver cancer, we assessed diethylnitrosamine (DEN)-mediated tumour caspase-2-deficient (Casp2−/−) mice. Following DEN injection young animals, was monitored for 10 months. We found that DEN-treated Casp2−/− mice have dramatically elevated burden...
Macropinocytosis is an actin-dependent mode of nonselective endocytosis that mediates the uptake extracellular fluid-phase cargoes. It now well recognized tumor cells exploit macropinocytosis to internalize macromolecules can be catabolized and used support cell growth proliferation under nutrient-limiting conditions. Therefore, identification molecular mechanisms control fundamental understanding metabolic adaptive landscape cells. Here, we report acetyl-CoA–producing enzyme, ATP citrate...
Caspase-2 has been implicated in various cellular functions, including cell death by apoptosis, oxidative stress response, maintenance of genomic stability and tumor suppression. The loss the caspase-2 gene (Casp2) enhances oncogene-mediated tumorigenesis induced E1A/Ras athymic nude mice, also Eμ-Myc lymphoma MMTV/c-neu mammary mouse models. To further investigate function tumorigenesis, we extended our studies TH-MYCN transgenic model neuroblastoma. Surprisingly, found that delayed...
Abstract Prostate cancers adapt to androgen receptor (AR) pathway inhibitors and progress castration resistance due ongoing AR expression function. To counter this, we developed a new approach modulate the inhibit castration-resistant prostate cancer (CRPC) using multivalent peptoid conjugates (MPC) that contain multiple copies of AR-targeting ligand ethisterone attached peptidomimetic scaffold. Here, investigated antitumor effects compound MPC309, trivalent display conjugated oligomer...
<p>Chemical structures and IC50 of the multivalent ethisterone-peptoid conjugate</p>
<p>Figure legends for the supplemental data</p>
<p>PK of MPC309 and effects on immune cells</p>
<p>Figure legends for the supplemental data</p>
<p>PK of MPC309 and effects on immune cells</p>
<p>Effects of MPC309 versus ethisterone on gene expression in LNCaP-abl cells</p>
<p>Comparison of MPC309 antiproliferative activity in DU145, PC3, LNCaP and 22Rv1 effects on AR-dependent gene expression</p>