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Francesco Ramirez

  • PROFESSOR Pharmacology and Systems Therapeutics
  • PROFESSOR Orthopaedics
  • PROFESSOR Medicine, Cardiology
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  • 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.


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.

For more information, please visit the Ramirez Laboratory website.


Nistala H, Lee-Arteaga S, Carta L, Cook JR, Smaldone S, Siciliano G, Rifkin AN, Dietz HC, Rifkin DB, Ramirez F. Differential effects of alendronate and losartan therapy on osteopenia and aortic aneurysm in mice with severe Marfan syndrome. Hum Mol Genet 2010 Dec; 19(24): 4790-4798.

Nistala H, Lee-Arteaga S, Smaldone S, Siciliano G, Ramirez F. Extracellular microfibrils control osteoblast-supported osteoclastogenesis by restricting TGFbeta stimulation of RANKL production. J Biol Chem 2010 Oct; 285(44): 34126-34133.

Nistala H, Lee-Arteaga S, Smaldone S, Siciliano G, Carta L, Ono RN, Sengle G, Solis-Arteaga E, Levasseur R, Ducy P, Sakai LY, Karsenty G, Ramirez F. Fibrillin-1 and -2 differentially modulate endogenous TGFbeta and BMP bioavailability during bone formation. J Cell Biol 2010 Sep; 190(6): 1107-1121.

Ramirez F, Rifkin DB. Extracellular microfibrils: contextual platforms for TGFbeta and BMP signaling. Curr Opin Cell Biol 2009 Oct; 21(5): 616-622.

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

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.

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.

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Ramirez did not report having any of the following types of financial relationships with industry during 2015 and/or 2016: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website. Patients may wish to ask their physician about the activities they perform for companies.

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