Gender	Male
E-mail	philippe.soriano@mssm.edu
Education and Training	Ph.D., University of Paris

Our laboratory studies signaling pathways that have important roles in mouse embryonic development.  For more detailed information, please consult our departmental website.

Education and Training	Ph.D., University of Paris

Research Interests: Vertebrate Developmental Signaling

Clinical Interests: Human developmental/congenital defects

Research in this laboratory is centered on the genetic analysis of mouse development, with a particular emphasis on genes implicated in growth factor signaling pathways. Using gene targeting in embryonic stem (ES) cells, we have shown that platelet derived growth factor (PDGF) signaling is critical for normal development of the vasculature, cranial and cardiac neural crest cells, the somites, and oligodendrocytes. We have studied the role of fibroblast growth factor (FGF) signaling in mesodermal and neural development, and are focusing on the role of this pathway in stem cell development in the early embryo. We are also developing mice carrying small mutations that prevent various effectors from docking to the receptors, to unravel the role of various signal transduction pathways in a physiological context. Last, we are creating activating mutations in PDGF receptors to provide information on the role of this signaling pathway in the control of normal cell proliferation and cancer.

To identify downstream targets of growth factor signaling and their physiological role, we are using gene trap mutagenesis in ES cells. In this approach, a promoterless reporter gene (for instance encoding b galactosidase) is introduced in ES cells. Expression of the reporter gene only occurs if it has disrupted an endogenous locus, typically leading to a null allele. Using a platform in which gene trap mutagenesis is coupled to DNA microarrays, we have identified and mutated numerous genes whose expression is regulated by PDGF. We are also performing gain of function screens on sensitized backgrounds to identify new signal transduction pathways that control neural crest cell behavior.

We are studying the involvement of other signaling pathways, in particular ephrin signaling, that regulate neural crest cell development. Eph receptors and ephrins function as an unusual receptor/ ligand pair that can activate both forward signaling to Eph receptors as well as reverse signaling through the ephrin GPI-anchor or cytoplasmic domain. We are studying the signaling pathways through which ephrin-B1 regulates cranial neural crest development and ephrin- B2 regulates trunk neural crest development. We have also shown that ephrin signaling can mediate boundary formation during development by regulating gap junction communication.

Olson LE, Soriano P. Increased PDGFRalpha activation disrupts connective tissue development and drives systemic fibrosis . Developmental Cell 2009; 16: 303-313.

Schmahl J, Rizzolo K, Soriano P. The PDGF signaling pathway controls multiple steroid producing lineages. Genes and Development 2008; 22: 3255-3267.

Schmahl J, Raymond CS, Soriano P. PDGF signaling specificity is mediated through multiple immediate early genes. Nature Genetics 2007; 39: 52-60.

Davy A, Bush JO, Soriano P. Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies cranio-frontonasal syndrome. PLOS Biology 2006; 4: 1763-1776.

Hoch RV, Soriano P. Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development. Development 2006; 133: 663-673.

Davy A, Aubin J, Soriano P. Ephrin-B1 forward and reverse signaling are required during mouse development. Genes Dev 2004; 18: 572-583.

Chen WV, Delrow J, Corrin PD, Frazier JP, Soriano P. Identification and Validation of PDGF transcriptional targets by microarray-coupled gene trap mutagenesis. Nature Genetics 2004; 36: 304-312.

Tallquist MD, French WJ, Soriano P. Additive effects of PDGF receptor b signaling pathways in vascular smooth muscle cell development. PLOS Biology 2003; 1: 288-299.

Hoch RV, Soriano P. PDGF roles in animal development. Development 2003; 130: 4769-4784.

Klinghoffer RA, Hamilton TG, Hoch R, Soriano P. An allelic series at the PDGFaR locus indicates unequal contributions of distinct signaling pathways during development. Developmental Cell 2002; 2: 103-113.