Dr Adam Walker


Research Fellow, Director of Laboratory of Immunopsychiatry, Neuroscience Research Australia Senior Lecturer, UNSW, School of Medicine

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Dr Adam Walker completed his PhD in psychology at the University of Newcastle in 2011. He spent a year at the University of Illinois as a postdoctoral researcher in the lab of integrative immunophysiology, followed by three years in Houston, Texas as a postdoctoral researcher at the MD Anderson Cancer Center. Here, Adam explored the neuroimmunology of cancer-related symptoms. He returned to Australia in 2015 and joined Monash University as a National Breast Cancer Foundation research fellow, investigating the mechanisms underlying cognitive and psychiatric side-effects of cancer and its treatment. Now at NeuRA, Adam’s research focuses on mechanisms of inflammation-induced depression and schizophrenia and cancer-associated cognitive impairment.


Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells.

Peterson AL, Walker AK, Sloan EK, Creek DJ

Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect-an increase in glycolytic activity at the expense of oxidative phosphorylation-and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions.

β2-Adrenoceptors on tumor cells play a critical role in stress-enhanced metastasis in a mouse model of breast cancer.

Chang A, Le CP, Walker AK, Creed SJ, Pon CK, Albold S, Carroll D, Halls ML, Lane JR, Riedel B, Ferrari D, Sloan EK

Chronic stress accelerates metastasis – the main cause of death in cancer patients – through the activation of β-adrenoceptors (βARs). We have previously shown that β2AR signaling in MDA-MB-231(HM) breast cancer cells, facilitates invadopodia formation and invasion in vitro. However, in the tumor microenvironment where many stromal cells also express βAR, the role of β2AR signaling in tumor cells in metastasis is unclear. Therefore, to investigate the contribution of β2AR signaling in tumor cells to metastasis in vivo, we used RNA interference to generate MDA-MB-231(HM) breast cancer cells that are deficient in β2AR. β2AR knockdown in tumor cells reduced the proportion of cells with a mesenchymal-like morphology and, as expected, reduced tumor cell invasion in vitro. Conversely, overexpression of β2AR in low metastatic MCF-7 breast cancer cells induced an invasive phenotype. Importantly, we found that knockdown of β2AR in tumor cells significantly reduced the impact of stress on metastasis in vivo. These findings highlight a crucial role for β2AR tumor cell signaling in the adverse effects of stress on metastasis, and indicate that it may be necessary to block β2AR on tumor cells to fully control metastatic progression.

Sickness behavior induced by cisplatin chemotherapy and radiotherapy in a murine head and neck cancer model is associated with altered mitochondrial gene expression.

Vichaya EG, Molkentine JM, Vermeer DW, Walker AK, Feng R, Holder G, Luu K, Mason RM, Saligan L, Heijnen CJ, Kavelaars A, Mason KA, Lee JH, Dantzer R

The present study was undertaken to explore the possible mechanisms of the behavioral alterations that develop in response to cancer and to cancer therapy. For this purpose we used a syngeneic heterotopic mouse model of human papilloma virus (HPV)-related head and neck cancer in which cancer therapy is curative. Mice implanted or not with HPV+ tumor cells were exposed to sham treatment or a regimen of cisplatin and radiotherapy (chemoradiation). Sickness was measured by body weight loss and reduced food intake. Motivation was measured by burrowing, a highly prevalent species specific behavior. Tumor-bearing mice showed a gradual decrease in burrowing over time and increased brain and liver inflammatory cytokine mRNA expression by 28 days post tumor implantation. Chemoradiation administered to healthy mice resulted in a mild decrease in burrowing, body weight, and food intake. Chemoradiation in tumor-bearing mice decreased tumor growth and abrogated liver and brain inflammation, but failed to attenuate burrowing deficits. PCR array analysis of selected hypoxia and mitochondrial genes revealed that both the tumor and chemoradiation altered the expression of genes involved in mitochondrial energy metabolism within the liver and brain and increased expression of genes related to HIF-1α signaling within the brain. The most prominent changes in brain mitochondrial genes were noted in tumor-bearing mice treated with chemoradiation. These findings indicate that targeting mitochondrial dysfunction following cancer and cancer therapy may be a strategy for prevention of cancer-related symptoms.

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