da Silva
Cleide G. da Silva, Ph.D.
Department of Surgery
Division of Vascular Surgery

Beth Israel Deaconess Medical Center
Harvard Medical School

330 Brookline Avenue, RN370-E
Boston, MA 02215
Office Phone: 617-667-0422
Office Fax: 617-667-0445


Cleide da Silva received her Bachelor’s Degree in Pharmacy in 1997 and her Specialist degree in Clinical Analysis in 1999 from the Federal University of Rio Grande do Sul, Porto Alegre, Brazil. She obtained her Masters (1999) and PhD (2003) in Biological Sciences – Biochemistry with emphasis on Neuroscience from the Federal University of Rio Grande do Sul, Porto Alegre, Brazil. She had her first Faculty appointment as Assistant Professor at the Pontificia Universidade Catolica do Rio Grande do Sul, College of Pharmacy, Porto Alegre, Brazil, where she taught Clinical Biochemistry and Clinical Immunology from 2000 to 2005. She then joined as a post-doctoral research fellow the laboratory of Dr. Elzbieta Kaczmarek in the Division of Gastroenterology and the Department of Medicine at the Beth Israel Deaconess Medical Center – Harvard Medical School – where she worked from 2005 until 2006 on purinergic signaling and vascular biology. She subsequently transferred as a post-doctoral fellow to the laboratory of Dr. Christiane Ferran, Division of Vascular and Endovascular Surgery, Department of Surgery, Beth Israel Deaconess Medical Center where she studied the role of the anti-inflammatory protein A20 in vascular remodeling and liver regeneration. After completing 2 years of post-doctoral fellowship in Dr. Ferran’s laboratory, Dr. da Silva was recruited in 2008 to join the Faculty of the Division of Vascular and Endovascular Surgery and was appointed as Instructor of Surgery at Harvard Medical School.

Research Interests: Neuroinflammation – Stroke – Endothelial Permeability – Vascular Biology


Basic Research - Combining expertise in the fields of neuroscience, vascular biology and inflammation, my research focuses on understanding the function(s) of anti-inflammatory protein A20 in the brain and exploring the potential of A20-based therapies to benefit neuroinflammatory and neurovascular diseases. Particularly, I am interested in studying the involvement of A20 in the pathophysiology of the brain damage that occurs following ischemic stroke, with emphasis on neuroinflammation and blood brain barrier disruption. Using a combination of cell culture techniques and mouse models of ischemic stroke, we have demonstrated that lower A20 expression causes spontaneous neuroinflammation and sensitizes A20 heterozygous mice to brain injury induced by ischemia/reperfusion. We have also shown that A20 combines potent anti-inflammatory functions in endothelium and glia, in addition to anti-apoptotic functions in endothelial cells, making it an ideal candidate to treat and/or contain the damage associated with neuroinflammatory and neurodegenerative diseases. Using the latest technological advances in gene therapy vectors, we are developing novel A20-based therapeutic tools to advance this goal.

New and Noteworthy Publications:

Guedes, Renata P; Csizmadia, Eva; Moll, Herwig P; Ma, Averil; Ferran, Christiane; da Silva, Cleide G.. A20 deficiency causes spontaneous neuroinflammation in mice. J Neuroinflammation. 2014 Jul 16;11:122. . This is the first characterization of spontaneous neuroinflammation caused by total or partial loss of A20, suggesting its key role in maintenance of nervous tissue homeostasis, particularly control of inflammation. These findings carry strong clinical relevance in that they question implication of identified A20 SNPs that lower A20 expression/function (phenocopying A20 HT mice) in the pathophysiology of neuroinflammatory diseases.

Da Silva, Cleide G; Studer, Peter; Skroch, Marco; Mahiou, Jerome; Minussi, Darlan C; Peterson, Clayton R; Wilson, Suzhuei W; Patel Virenda I; Ma, Averil; Csizmadia, Eva; Ferran, Christiane.. A20 promotes liver regeneration by decreasing SOCS3 expression to enhance IL-6/STAT3 proliferative signals. Hepatology. 2013 May;57(5):2014-25. PMCID: PMC3626749. . Data presented in this paper demonstrates that A20 enhances IL-6/STAT3 pro-proliferative signals in hepatocytes by down-regulating SOCS3, likely through a miR203-dependent manner. This finding together with previously stablished inhibitory effect of A20 on expression levels of the potent cell cycle brake p21 establishes its pro-proliferative properties in hepatocytes and prompts the pursuit of A20-based therapies to promote liver regeneration and repair.

Silva, Cleide G, Specht, Anna; Wegiel, Barbara; Ferran, Christiane; Kaczmarek, Elzbieta.. Mechanism of purinergic activation of endothelial nitric oxide synthase in endothelial cells. Circulation 2009; 119(6):871-879.. This study demonstrates that extracellular nucleotides ATP, UTP and ADP mediate eNOS phosphorylation via P2Yreceptor activation, in a calcium and protein kinase C delta dependent manner. This newly identified signaling pathway opens new therapeutic avenues for the treatment of endothelial dysfunction.

Silva, Cleide G; Jarzyna, Robert; Specht, Anna; Kaczmareck, Elzbieta.. Extracellular Nucleotides and Adenosine Independently Activate AMP-Activated Kinase in Endothelial Cell: Involvement of P2 Receptors and Adenosine Transporters. Circ. Res. 2006;98:e39-e47. . In this paper, we demonstrate, 2 distinct but converging pathways of AMPK activation in endothelial cells. One induced by extracellular nucleotides, linked to P2Y1, P2Y2, and/or P2Y4 receptors, dependent on Ca2+ and CaMKK. The second induced by adenosine uptake with the involvement of adenosine transporters, followed by the generation of (intracellular) AMP, and activation of AMPK, with LKB1 as a putative upstream kinase. In an in vivo situation, nucleotides are finally hydrolyzed to adenosine. Therefore, the 2 mechanisms of AMPK activation, nucleotide and adenosine dependent, can operate at the same time. Considering that local nucleotides and adenosine concentrations under pathophysiological conditions can be substantially increased, this pathway could play an important role in restoring the energy balance by AMPK activation that modulates glucose uptake and fatty acid metabolism.

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