More dementia research funded at QBI
Published on: 7 August 2017
About
Brain disorders are among the most serious health problems facing modern society. Many of these disorders become more common with advancing age, including Alzheimer’s disease, Parkinson’s disease, stroke, amyotrophic lateral sclerosis (ALS), and many others. The burden of these neurodegenerative diseases is growing inexorably as the population ages, with enormous economic and human costs.
Some neurodegenerative conditions, such as Huntington’s disease or familial ALS, have clear genetic causes. Others involve complex interactions of genetic and environmental influences that can affect the brain in many ways. Our work at the Neurula Lab spans the gamut from genetic studies of animal models to imaging studies of human clinical patients. We are working to understand the basic brain mechanisms that are affected by these diseases and to determine how the brain responds to therapeutic interventions. The answers to these fundamental questions will form the foundation for new clinical treatments. We also aim to identify the life-style factors that promote wellness and "successful aging." For those suffering from age-related memory or motor problems, our goal is to diagnose the disease, identify means for effectively treating it, and provide help to families and caregivers.
Research Areas
- Alzheimer's disease
- Immunology
- Neurodegenerative disease
- Ageing brain
Role of the immune system in neurodegeneration
Dr Medeiros discovered that Alzheimer's disease promotes defects in fundamental molecular events that limit and resolve inflammation, and demonstrated that such changes account for a substantial portion of the disease pathogenesis. Currently, his lab is undertaking the challenge of using and developing novel animal models in parallel with studies on affected human subjects to elucidate the underlying molecular mechanisms linking inflammation to β-amyloid, tau pathology and cognitive decline. Understanding these mechanisms will allow definition of the biological pathways involved in the onset and progression of Alzheimer’s disease, and identify potential therapeutic targets for the management of this devastating disorder.
Impact of comorbidities in brain ageing and disease
The Neurula Lab also studies the impact of comorbidities in neurodegeneration and Alzheimer’s disease. We seek to understand how concurrent diseases that commonly occur in the elderly may modulate neurodegeneration and age-related changes in the brain. We have been particularly interested in bacterial infections and diabetes as major regulators of biological processes, and are developing genetic and pharmacological agents to manipulate these pathways in Alzheimer’s disease.
Fisher A, Bezprozvanny I, Wu L, Ryskamp DA, Bar-Ner N, Natan N, Brandeis R, Elkon H, Nahum V, Gershonov E, LaFerla FM, Medeiros R (2016) AF710B, a novel M1/σ1 agonist with therapeutic efficacy in animal models of Alzheimer's disease. Neurodegener. Dis.16: 95-110.
Dunn HC, Ager RR, Baglietto-Vargas D, Cheng D, Kitazawa M, Cribbs DH, Medeiros R (2015) Restoration of lipoxin A4 signaling reduces Alzheimer's disease-like pathology in the 3xTg-AD mouse model. J. Alzheimer’s Dis. 43: 893-903.
Medeiros R, Castello NA, Cheng D, Kitazawa M, Baglietto-Vargas D, Green KN, Esbenshade TA, Bitner RS, Decker MW, LaFerla FM (2014) α7 nicotinic receptor agonist enhances cognition in aged 3xTg-AD mice with robust plaques and tangles. Am. J. Pathol. 184: 520-529.
Medeiros R, Kitazawa M, Passos GF, Baglietto-Vargas D, Cheng D, Cribbs DH, LaFerla FM (2013) Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduces Alzheimer disease-like pathology in mice. Am. J. Pathol. 182: 1780-1789.
Medeiros R, LaFerla FM (2013) Astrocytes: conductors of the Alzheimer disease neuroinflammatory symphony. Exp. Neurol. 239: 133-138.
Medeiros R, Chabrier MA, LaFerla FM (2013) Elucidating the triggers, progression, and effects of Alzheimer's disease. J. Alzheimer’s Dis..Suppl. 1: S195-S210.
Medeiros R, Kitazawa M, Chabrier MA, Cheng D, Baglietto-Vargas D, Kling A, Moeller A, Green KN, LaFerla FM (2012) Calpain inhibitor A-705253 mitigates Alzheimer's disease-like pathology and cognitive decline in Aged 3xTg-AD mice. Am. J. Pathol.181: 616-625.
Medeiros R, Kitazawa M, Caccamo A, Baglietto-Vargas D, Estrada-Hernandez T, Cribbs DH, Fisher A, LaFerla FM (2011) Loss of muscarinic M1 receptor exacerbates Alzheimer's disease-like pathology and cognitive decline. Am. J. Pathol.179: 980-991.
Medeiros R, Baglietto-Vargas D, LaFerla FM (2011) The role of tau in Alzheimer's disease and related Disorders. CNS Neurosci. Ther. 17: 514-524.
Medeiros R, Figueiredo CP, Pandolfo P, Duarte FS, Prediger RD, Passos GF, Calixto JB (2010) The role of TNF-α signaling pathway on COX-2 upregulation and cognitive decline induced by β-amyloid peptide. Behav. Brain Res. 209: 165-173.
Medeiros R, Prediger RD, Passos GF, Pandolfo P, Duarte FS, Franco JL, Dafre AL, Di Giunta G, Figueiredo CP, Takahashi RN, Campos MM, Calixto JB (2007) Connecting TNF-α signaling pathways to iNOS expression in a mouse model of Alzheimer's disease: relevance for the behavioral and synaptic deficits induced by β-amyloid protein. J. Neurosci. 27: 5394-5404.
Since 2008, Dr Medeiros has led the effort to identify the underlying mechanisms related with the development and progression of neurodegenerative diseases. His long-term goal is to advance knowledge of healthy, and diseased, brain function to a point where rational strategies can be developed for the prevention and cure of age-related neurological disorders. To pursue his research goals, Dr Medeiros maintains a research environment in which creative and innovative ideas can be nurtured and brought to fruition using a base of established as well as state-of-the-art approaches. His belief is that this environment will facilitate conceptual leaps in our understanding of the diseases that impact the human brain.
The following projects may be suitable for either Honours or PhD.
Project 1
Role of the immune system in neurodegeneration
Dr Medeiros discovered that Alzheimer's disease promotes defects in fundamental molecular events that limit and resolve inflammation, and demonstrated that such changes account for a substantial portion of the disease pathogenesis. Currently, the Neurula lab is undertaking the challenge of using and developing novel laboratory models in parallel with studies on affected human subjects to elucidate the underlying molecular mechanisms linking inflammation to β-amyloid, tau pathology and cognitive decline. Understanding these mechanisms will allow definition of the biological pathways involved in the onset and progression of Alzheimer’s disease, and identify potential therapeutic targets for the management of this devastating disorder.
Project 2
Impact of comorbidities in brain ageing and disease
The Neurula Lab also studies the impact of comorbidities in neurodegeneration and Alzheimer’s disease. We seek to understand how concurrent diseases that commonly occur in the elderly may modulate neurodegeneration and age-related changes in the brain. We have been particularly interested in infections, diabetes and traumatic brain injury as major regulators of biological processes, and are developing genetic and pharmacological agents to manipulate these pathways in Alzheimer’s disease.
Techniques you will learn in our group may include: Primary glial and neuronal cell cultures, intracranial delivery of viral vectors, western blot, immunohistochemistry (IHC), immunocytochemistry (ICC) and immunofluorescence (IF).
Impact of interleukin-18 on Alzheimer's disease
(2017–2019) NHMRC Project Grant
Investigating interleukin-37 as a treatment and biomarker for Alzheimer's disease
(2017–2019) NHMRC Project Grant