Roberto Pola, MD, PhD. Assistant Professor Center of Cancer Systems Biology Caritas St.Elizabeth's Medical Center Tufts University School of Medicine 736 Cambridge Street Boston, MA 02135   Tel: 617.562.7275 Mail: Roberto.Pola [at] tufts.edu

Education and Training:
Dr. Pola received his MD in 1996 from the Catholic University School of Medicine of Rome, Italy, and his PhD in Molecular Biology in 2001 from the same School. He completed clinical training with a residency in geriatrics at the A. Gemelli University Hospital in Rome, Italy, where he was also the head of the Laboratory of Vascular Biology and Genetics. He worked as a postdoctoral fellow at St. Elizabeth's Medical center in the laboratory of the late Jeffrey Isner and served as a Visiting Assistant Professor in the Department of Anatomy and Cell Biology at Tufts University School of Medicine just prior to his current appointment at St. Elizabeth's. He is currently an Associate Investigator at the Center of Cardiovascular Research and an Assistant Professor of Medicine at Tufts University School of Medicine. He also has an adjunct appointment at the Center of Cancer Systems Biology of Tufts University School of Medicine and the Department of Medicine of the Catholic University School of Medicine of Rome, Italy. Dr. Pola has published more than 80 papers in peer-reviewed scientific journals. He receives grants from the NIH, the Italian Ministry of University and Research, and various foundations.

Research Interests:

Molecular and cellular mechanisms of angiogenesis and vasculogenesis
• stem cells and tissue regeneration
• genetics of cardiovascular diseases

One of the major topics of Dr. Pola's research is the investigation of the angiogenic abilities of the morphogen Sonic hedgehog (Shh) in adult tissues. The basic hypothesis is that signaling pathways that are important during the embryonic development of the cardiovascular system may be post-natally re-activated in pathologic and physiologic conditions that are associated with tissue regeneration. Dr. Pola provided the first demonstration that the Shh signaling pathway is physiologically relevant in response to ischemia in the adult, and that Shh is an indirect angiogenic agent able to upregulate different families of growth factors, such as VEGF, angiopoietin-1, and angiopoietin-2, thus stimulating both angiogenesis and arteriogenesis. Dr. Pola has also provided evidence that Shh recombinant protein may be used to induce therapeutic angiogenesis in experimental models of limb ischemia and diabetic peripheral neuropathy. More recently, he has used a plasmid encoding human Shh to induce revascularization of the ischemic myocardium and enhance heart function. These positive effects appear to be mediated also by stimulation of vasculogenesis, as indicated by the ability of Shh to upregulate SDF-1α and increase the number of bone marrow-derived endothelial progenitor cells in the ischemic myocardium. Dr. Pola is also conducting studies to identify the relationship existing between hypoxia and the activation of the Shh signaling pathway.

Dr. Pola has an extensive experience in mouse, rat, rabbit, and pig models of heart and limb ischemia, as well as in models to study the contribution of stem cell to neovascularization, such as the bone marrow transplantation model in mice. Dr. Pola has also developed animal models of skin, skeletal muscle, peripheral nerve, and inner ear injury and is studying the effects of Shh and other angiogenic molecules in these settings. In particular, recent data from Dr. Pola’s laboratory suggest that, in addition to stimulate angiogenesis and vasculogenesis, Shh might also have direct myogenic properties. Indeed, in the injured skeletal muscle, activated satellite cells respond to Shh stimulation in vivo.

Dr. Pola also investigates the role of inflammatory gene polymorphisms in cardiovascular diseases. He has generated a large database containing demographic, clinical, and genetic information on patients affected by peripheral artery occlusive disease, stroke, and vascular dementia. Dr. Pola has shown that pro-inflammatory genetic profiles, determined by the synergistic interactions between single nucleotide polymorphisms, increase the risk for ischemic stroke in the elderly. Dr. Pola is now testing a multigenic model of stroke risk in a prospective cohort study of subjects affected by diabetes. He is also collaborating with international biotech companies to identify genetic markers for peripheral artery occlusive disease, abdominal aortic aneurysm, and myocardial infarction.

Selected Publications:

• Schratzberger P., Walter D.H., Rittig K., et al. (2001) Reversal of experimental diabetic neuropathy by VEGF gene transfer. J Clin Invest 107: 1083-1092
• Pola R., Ling L., Silver M., et al. (2001) Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors. Nature Medicine 7: 706-711
• Pola R., Flex A., Gaetani E., et al. (2003) Synergistic effect of –174 G/C polymorphism of the IL-6 gene promoter and 469 E/K polymorphism of the ICAM-1 gene in Italian patients with history of ischemic stroke. Stroke 34: 881-885
• Pola R., Ling L.E., Aprahamian T.R., et al. (2003) Postnatal recapitulation of embryonic hedgehog pathway in response to skeletal muscle ischemia. Circulation 108: 479-485
• Pola R., Gaetani E., Flex A., et al. (2003) Peripheral nerve ischemia: apoliprotein-E deficiency results in impaired functional recovery and reduction of associated intraneural angiogenic response. Exp Neurol 184: 264-273
• Pola R., Gaetani E., Flex A., et al. (2004) Comparative analysis of the in vivo angiogenic properties of stable prostacyclin analogs: a possible role for peroxisome proliferator-activated receptors. J Mol Cell Cardiol 36: 363-370
• Danese S., Scaldaferri F., Papa A., et al. (2004) CD40L-positive platelets induce CD40L expression de novo in endothelial cells: adding a loop to microvascular inflammation. Arterioscler Thromb Vasc Biol 24: e162
• Flex A., Gaetani E., Papaleo P., et al. (2004) Proinflammatory genetic profiles in subjects with history of ischemic stroke. Stroke 35: 2270-2275
• Kusano K.F., Allendoerfer K.L., Munger W., et al. (2004) Sonic hedgehog induces arteriogenesis in diabetic vasa nervorum and restores function in diabetic neuropathy. Arterioscler Thromb Vasc Biol 24: 2102-2107
• Pola R., Aprahamian T.R., Bosch-Marcé M., et al. (2004) Age-dependent VEGF expression and intraneural vascularization during regeneration of peripheral nerves. Neurobiol Aging 25: 1361-1368
• Kusano K.F., Pola R., Toshinori M., et al. (2005) Sonic hedgehog myocardial gene therapy: Tissue repair through transient reconstitution of embryonic signaling. Nature Medicine 11: 1197-1204
• Danese S., Sans M., de la Motte C., et al. (2006) Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 130: 2060-2073
• Flex A., Gaetani E., Angelini F., et al. (2007) Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia. J Intern Med 262: 124-130
• Helgadottir A., Thorleifsson G., Magnusson K.P., et al. (2008) The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nature Genetics 40: 217-224
• Biscetti F., Gaetani E., Flex A., et al. (2008) Selective activation of peroxisome proliferator-activated receptor (PPAR)a and PPARg induces neoangiogenesis through a vascular endothelial growth factor-dependent mechanism. Diabetes 57: 1394-1404
• Biscetti F., Gaetani E., Flex A., et al. (2008) Peroxisome Proliferator-Activated Receptor Alpha is crucial for iloprost-induced in vivo angiogenesis and Vascular Endothelial Growth Factor upregulation. J Vasc Res 46: 103-108
• Biscetti F., Pola R. (2008) Endothelial progenitor cells and angiogenesis join the PPARty. Circulation Res103: 7-9
• Thorgeirsson T.E., Geller F., Sulem P., et al. (2008) A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. Nature 452: 638-642
• Straface G., Aprahamian T., Flex A., et al. (2008) Sonic Hedgehog Regulates Angiogenesis and Myogenesis During Post-Natal Skeletal Muscle Regeneration. J Cell Mol Med Jul 26 [ePub ahead of print]