Francesco Ramirez, PhD
- PROFESSOR | Pharmacological Sciences
- PROFESSOR | Orthopaedics
- PROFESSOR | Medicine, Cardiology
Research Topics:Cardiovascular, Cell Biology, Extracellular Matrix, Genetics, Growth Factors and Receptors, Knockout Mice, Molecular Biology, Organogenesis, Skeletal Biology
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.
Multi-Disciplinary Training AreaBiophysics and Systems Pharmacology [BSP]
DSc, 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.
For more information, please visit the Ramirez Laboratory website.