Gender	Male
E-mail	francesco.ramirez@mssm.edu
Education and Training	D.Sc., Universita degli Studi di Palermo
	Postdoctoral Training, Columbia University

Dr. Ramirez is the Dr. Amy and James Elster Chair of Molecular Biology (Connective Tissue Diseases) and Professor of Pharmacology and Systems Therapeutics, and of Medicine-Cardiology.

Trained as a molecular geneticist and developmental biologist, Dr. Ramirez' research interest is the study of congenital and acquired disorders of the connective tissue to delineate the role of the extracellular matrix in embryonic development, postnatal growth and adult homeostasis, and to identify biological targets for therapeutic intervention in Marfan syndrome and scleroderma. Recent reviews in Current Opinion in Genetics and Development and Current Opinion in Cell Biology describe his mouse studies implicating fibrillin assemblies in the extracellular control of TGF-B and BMP signaling and their translation into a new therapy against aneurysm progression in Marfan syndrome.

Education and Training	D.Sc., Universita degli Studi di Palermo
	Postdoctoral Training, Columbia University

Our laboratory is interested in the characterization of the multiple roles that the extracellular matrix plays during vertebrate organogenesis, and in congenital and acquired disorder of the connective tissue. We are currently focused on the characterization of pathophysiological mechanisms in Marfan syndrome and scleroderma using a combination of in vivo and ex vivo approaches. Our long-term goal is to identify suitable biological targets for therapeutic interventions against these life-threatening diseases.

Marfan syndrome is a common disorder of the connective tissue caused by mutations in fibrillin-1, the main structural component of extracellular microfibrils. We have shown that multisystem manifestations in Marfan syndrome are accounted for by the combined effects of impaired tissue integrity and promiscuous activation of TGF-B signals. We are studying the mechanisms whereby fibrillin-rich microfibrils regulate local TGF-B signals, and how dysregulation of this key function impairs morphogenesis and tissue homeostasis.

Excessive deposition of a disorganized collagen matrix resulting in loss of organ function is the hallmark of clinically distinct fibrotic conditions. Recent studies have implicated Ras stabilization by reactive oxygen species (ROS) in promoting and/or sustaining skin fibrosis in scleroderma. We are investigating the intracellular events downstream of the ROS/Ras loop leading to collagen up-regulation, as well as the functional relationship between the ROS/Ras and TGF-B signaling pathways in fibrogenesis.

Ramirez F, Dietz HC. Marfan syndrome: from molecular pathogenesis to clinical treatment. Curr Opin Genet Dev 2007; 17: 252-258.

Cohn RD, van Erp C, Habashi JP, Soleimani AA, Klein EC, Lisi MT, Gamradt M, ap Rhys CM, Holm TM, Loeys BL, Ramirez F, Judge DP, Ward CW, Dietz HC. Angiotensin II type 1 receptor blockade attenuates TGFb-induced failure of muscle regeneration in multiple myopathic states. Nature Med 2007; 13: 204-210.

Habashi JP, Judge DP, Holm TM, Cohn RD, Loeys BL, Coopers TK, Myers L, Klein EC, Liu G, Calvi C, Podowski M, Neptune ER, Halushka MK, Bedja D, Gabrielson K, Rifkin DB, Carta L, Ramirez F, Huso DL, Dietz HC. Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome. Science 2007; 312: 117-121.

Carta L, Pereira L, Emilio Arteaga-Solis E, Lee-Arteaga SY, Lenart B, Starcher B, Merkel CA, Sukoyan M, Kerkis A, Hazeki N, Keene DR, Sakai LY, Ramirez F. Fibrillins 1 and 2 perform partially overlapping functions during aortic development. J. Biol. Chem 2006; 281: 8016-8023.

Tanaka S, Antoniv TT, Lui K, Wang L, Wells DJ, Ramirez F, Bou-Gharios G. Cooperativity between far-upstream enhancer and proximal promoter elements of the human a2(I) collagen (COL1A2) gene instructs tissue specificity in transgenic mice. J. Biol. Chem 2004; 279: 56024-56031.

Sumiyoshi H, Mor N, Lee SY, Henderson S, Tanaka S, Yoshioka H, Rattan S, Ramirez F. Esophageal muscle physiology and morphogenesis require assembly of a collagen XIX-rich basement membrane zone. J. Cell Biol 2004; 166: 591-600.

Ramirez F, Dietz HC. Therapy Insight: aortic aneurysm and dissection in Marfan's syndrome. Nature Clin. Pract. Cardiovasc. Med 2004; 1: 31-36.

Neptune ER, Frischmeyer PA, Arking DE, Myers L, Bunton TE, Gayraud B, Ramirez F, Sakai LY, Dietz HC. Dysregulation of TGF-b activation contributes to pathogenesis in Marfan syndrome. Nature Genet 2003; 33: 407-411.

Arteaga-Solis E, Gayraud B, Lee SY, Shum L, Sakai L, Ramirez F. Regulation of limb patterning by extracellular microfibrils. J. Cell Biol 2001; 154: 275-281.

Zhang W, Ou J, Inagaki Y, Greenwel P, Ramirez F. Synergistic cooperation between Sp1 and Smad3/Smad4 mediates TGFb1 stimulation of a2(I) collagen (COL1A2) transcription. J. Biol. Chem 2000; 75: 39237-39245.