UHealth - University of Miami Health System

Roberta Brambilla

General Information

Roberta   Brambilla

Contact

  • Fax: 305-243-3914
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Languages

  • English
  • Italian

Roles

  • Research Assistant Professor

Research Interests

For over 10 years the main focus of my research has been understanding the role of neuroinflammation in the pathophysiology of neurodegenerative disorders (e.g., multiple sclerosis, spinal cord injury, neuropathic pain), with a specific interest in the contribution of glial cells. I have been pursuing these investigations using both in vitro and in vivo models. In collaboration with Dr. John Bethea, I participated in developing and characterizing a novel transgenic mouse (GFAP-IkBa-dominant negative mice) where the transcription factor NF-kB, a master regulator of inflammation, is inactivated specifically in astrocytes. With this model we produced the first in vivo evidence that selective inhibition of the astrocyte-driven inflammatory response leads to significant functional recovery after spinal cord injury, experimental autoimmune encephalomyelitis (a model of multiples sclerosis), and neuropathic pain.

Currently, my lab is focused on two specific areas of interest:

 

1) Investigating the role of tumor necrosis factor (TNF), both membrane-bound and soluble forms, in the processes of neuroinflammation, demyelination and remyelination in experimental autoimmune encephalomyelitis and spinal cord injury. We are especially interested in TNF signaling via TNFR2, the receptor that has been associated with neuroprotective and anti-inflammatory properties in the central nervous system. We have been studying TNFR2 function in vivo using pharmacological and genetic approaches, including cell-specific TNFR2 conditional knockout mice with ablation of TNFR2 in various central nervous system ad immune-cell populations that we developed in the lab.


2) Investigating whether mitochondrial dysfunction in oligodendrocytes plays a role in the pathophysiology of multiple sclerosis. Despite the general consensus on the autoimmune component of multiple sclerosis, its etiology remains unknown. Our hypothesis is that, at least in some forms of multiple sclerosis, a primary dysfunction of the central nervous system is the initial trigger of the disease, then followed by the destructive autoimmune response. Using a mouse model generated in our lab where we can induce timed mitochondrial DNA deletions specifically in myelinating oligodendrocytes to study whether primary oligodendropathy may represent the insult initiating the cascade of pathological events in MS.

Education

2000 Ph.D.
University of Milan
1995 M.Sci.
University of Milan
1993 B.S.
University of Milan

Publications

  • Brambilla R.*, Morton P.D., Ashbaugh J.J., Karmally S., Lambertsen K., and Bethea J.R. (2014) Astrocytes play a key role in EAE pathophysiology by orchestrating in the CNS the inflammatory response of resident and peripheral immune cells and by suppressing remyelination. GLIA, 62:452-457.
  • Dellarole A., Morton P., Brambilla R., Walters W., Summers S., Bernardes D., Grilli M., Bethea J.R. (2014) Neuropathic pain-induced depressive-like behavior and hippocampal neurogenesis and plasticity are dependent on TNFR1 signaling. Brain Behav. Immun., 41:65-81.
  • Jopek Ashbaugh J., Brambilla R., Karmally S.A., Cabello C., Malek T.R., and Bethea J.R. (2013) IL7Ra contributes to EAE through altered T cell responses and non-hematopoietic cell lineages. J. Immunol., 190:4525-34.
  • Brambilla R., Couch Y., and Lambertsen K. (2013) The Effect of Stroke on Immune Function. Mol Cell Neurosci, 53:26-33.
  • Brambilla R.*, Dvoriantchikova G., Barakat D., Ivanov D., Bethea J.R., and Shestopalov V.I. (2012) Transgenic inhibition of astroglial NF-kappaB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis. J. Neuroinflammation, 9:213.
  • Brambilla R.*, Jopek Ashbaugh J., Magliozzi R., Dellarole A., Karmally S., Szymkowski D.E., and Bethea J.R. (2011) Inhibition of soluble tumor necrosis factor is therapeutic in experimental autoimmune encephalomyelitis and promotes axon preservation and remyelination. Brain, 134:2736-2754.
  • Fu E.S., Zhang Y.P., Sagen J., Candiotti K.A., Morton P.D., Liebl D.J., Bethea J.R., and Brambilla R. (2010) Transgenic inhibition of glial NF-kappa B reduces pain behavior and inflammation after peripheral nerve injury. Pain, 148:509-518.
  • Brambilla R.*, Hurtado A., Persaud T., Esham K., Pearse D.D., Oudega M., and Bethea J.R. (2009) Transgenic inhibition of astroglial NF-kappaB leads to increased axonal sparing and sprouting following spinal cord injury. J. Neurochem., 110:765-78
  • Brambilla R.*, Persaud T., Hu X., Karmally K., Shestopalov V.I., Dvoriantchikova G., Ivanov D., Nathanson L., Barnum S.R., and Bethea J.R. (2009) Transgenic inhibition of astroglial NF-kappaB improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J. Immunol., 182:2628-40.
  • Bracchi-Ricard V., Brambilla R., Levenson J., Hu W.-H., Bramwell A., Sweatt J.D., Green E.J., and Bethea J.R. (2008) Astroglial nuclear factor-kappaB regulates learning and memory and synaptic plasticity in female mice. J. Neurochem., 104:611-23
  • Brambilla R.*, Bracchi-Ricard V., Hu W.-H., Frydel B., Bramwell A., Karmally S., Green E.J., and Bethea J.R. (2005) Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J. Exp. Med., 202:145-56
  • Fumagalli M., Brambilla R.*, D’Ambrosi N., Volonte’ C., Matteoli M., Verderio C., and Abbracchio M.P. (2003) Nucleotide-mediated calcium signalling in rat cortical astrocytes: role of P2X and P2Y receptors. Glia, 43:218-230.
  • Brambilla R., Neary J.T., Cattabeni F., Cottini L., D'Ippolito G., Schiller P.C. and Abbracchio M.P. (2002) Induction of COX-2 by P2Y receptors in rat cortical astrocytes is dependent on ERK1/2 but independent of calcium signaling. J. Neurochem. 83: 1285-1296