Roberta Martinelli, PhD
Instructor in Medicine
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, RN-245
Boston, MA 02215
Roberta Martinelli earned a degree in Chemistry and Pharmacology from the University of Trieste and a PhD in Molecular Immunology from Imperial College, London. She was then a Senior Scientist at SR Pharma before returning to academia as a Senior Research Associate with Professor John Greenwood at UCL, London. In 2009 Dr. Martinelli joined the Center For Excellence in Vascular Biology at Brigham’s and Women Hospital and in 2010 the Department of Medicine and CVBR at Beth Israel Deaconess Medical Center.
Research Interests: Endothelial barrier / Angiogenesis
Basic Research: Our group is investigating the mechanisms of endothelial barrier maintenance and recovery in health and disease in particular through the use of advanced high-resolution imaging techniques and atomic force microscopy. We are interested in:
1) Molecular determinants of leukocyte diapedesis route
The endothelium constitutes a physical barrier that is continuously breached by blood leukocytes during trans-endothelial migration. This occurs by leukocytes either passing directly through individual endothelial cells (i.e., a ‘transcellular’ route) or between them (i.e., a ‘paracellular’ route). Why two different routes exist, and what governs the specific subcellular loci that are breached, are open questions with important implications for overall barrier regulation. We propose that basic biomechanical properties of the endothelium are critical determinants of the migration pathways used to cross it. We are currently exploring these areas in settings of health and disease.
2) Biomechanical contribution of the endothelium and the extracellular matrix in the regulation of vascular permeability and angiogenesis.
While extensive studies have revealed a plethora of molecular players and signaling pathways that regulate vascular integrity, an integrated view of the cellular regulation of mechanisms for this process is still lacking. To overcome this hurdle, we are implementing coordinated investigation of cytoskeletal, biomechanical and signaling dynamics in novel models systems that introduce physiologic flow, matrix composition/stiffness and oxygen tension.
3) Bedside-to-Bench exploration of Sepsis toward a novel cell biologic understanding of pathogenesis.
Though a unique partnership with the Department of Emergency Medicine, we have developed new methods to assess aberrations in neutrophil behavior during sepsis and are using this approach to better understand the contribution of neutrophils to disease and in particular vascular dysfunction.
New and Noteworthy Publications:
Martinelli R, Zeiger AS, Whitfield M, Sciuto TE, Dvorak AM, Van Vliet KJ, Greenwood J, Carman CV. Probing the Biomechanical Contribution of the Endothelium to Lymphocyte Migration: Diapedesis by the Path of Least Resistance. Journal Cell Science, 2014, In press. This paper investigates how leukocytes feel the endothelium to find appropriate loci for transmigration and forwards the new concept of “tenertaxis” (Latin tener, soft, tenuous).
Zonneveld R, Martinelli R, Shapiro NI, Kuijpers TW, Plotz FB, Carman CV.Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults. Crit Care. 2014; 18(1):204. This paper review the current state of the art in sepsis biomarker research and forwards a new hypothesis to concomitantly monitor both soluble adhesion markers and circulating sheddases.
Martinelli R, Kamei M, Sage PT, Massol R, Varghese L, Sciuto T, Toporsian M, Dvorak AM, Kirchhausen T, Springer TA, Carman CV. Release of cellular tension signals self-restorative ventral lamellipodia to heal barrier micro-wounds. J Cell Biol. 2013 Apr 29; 201(3):449-65. This paper reveals the incredible self-restorative capacity of the endothelium and identifies novel actin-rich ventral lamellipodia responsible of healing endothelial micro-wounds in a ROS dependent way.
Martinelli R, Gegg M, Longbottom R, Adamson P, Turowski P, Greenwood J. ICAM-1-mediated endothelial nitric oxide synthase activation via calcium and AMP-activated protein kinase is required for transendothelial lymphocyte migration. Mol Biol Cell. 2009 Feb; 20(3):995-1005. This paper shows for the first time the role of ICAM-1 mediated eNos activation in the control of lymphocyte transendothelial migration.
Turowski P, Martinelli R, Crawford R, Wateridge D, Papageorgiou AP, Lampugnani MG, Gamp AC, Vestweber D, Adamson P, Dejana E, Greenwood J. Phosphorylation of vascular endothelial cadherin controls lymphocyte emigration. J Cell Sci. 2008 Jan 1; 121(Pt 1):29-37. This paper shows the role of specific VEC-phosphorylation sites in the control of lymphocyte transendothelial migration.