Roberta Brambilla, Ph.D.
Associate Professor, Department of Neurological Surgery
Neuroinflammation and neuro-immune interactions in neurological disease
The main focus of my research is understanding the role of neuroinflammation in the pathophysiology of neurological disorders (e.g., multiple sclerosis, spinal cord injury, stroke), with a specific interest in the contribution of glial cells. We investigate astrocytes and microglia for their involvement in the neuroinflammatory response to injury, and oligodendrocytes and oligodendrocyte precursor cells for their role in axon myelination, metabolic support of neurons and myelin repair. We are also interested in the interaction between the immune system and the central nervous system (CNS), and how innate and adaptive immune responses driven by macrophages, T cells and B cells infiltrating into the CNS during disease influence neurological outcomes. Currently, our primary lines of research are centered on:
1) Understanding how tumor necrosis factor (TNF), both membrane-bound (tmTNF) and soluble (solTNF), as well as its receptors TNFR1 and TNFR2 participate in the processes of demyelination/remyelination and neuroinflammation. We demonstrated that tmTNF has a protective function in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), and this effect is mediated by the activation of TNFR2 in glial cells (Brambilla et al., Brain 2011; Madsen et al., J Neurosci, 2016; Gao et al., Cell Rep, 2017). This work supports the idea that TNFR2 can be exploited as a target for therapy, not only in MS but in other neurological disorders associated with inflammation and myelin damage. On this basis, our current work aims at: a) addressing the molecular mechanisms of TNFR2 protective functions in the CNS in various models of injury and disease (MS, spinal cord injury, traumatic brain injury, stroke); b) identifying selective TNFR2 agonists for the therapy of neurological disease.
2) Investigating whether mitochondrial dysfunction in oligodendrocytes plays a role in the pathophysiology of MS. Despite the general consensus on the autoimmune component of MS, its etiology remains unknown. An emerging view is that, at least in some forms of MS, a primary dysfunction within the CNS might be the initial trigger of the disease, then followed by the destructive autoimmune response. Our hypothesis is that mitochondrial dysfunction in oligodendrocytes is one of the causes of oligodendrocyte cell death and demyelination, leading to disease initiation. To investigate this hypothesis we use a transgenic mouse model generated in our lab where mitochondrial DNA (mtDNA) depletion can be timely and reversibly induced in myelinating oligodendrocytes (PLP:mtPstI mice, Madsen et al., 2017), leading to oligodendrocyte cell death and an MS-like phenotype. We are also addressing oligodendroglial mitochondrial function/dysfunction in CNS tissues from primary progressive MS patients with various approaches.
Roberta Brambilla, Ph.D.
- The Miami Project to Cure Paralysis
1095 NW 14th Terrace (R-48)
Miami, FL 33136
- (305) 243-7131
- (305) 243-3914
Society for Neuroscience
International Society for Neuroimmunology
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