Biographies

Marie-Dominique Filippi, PhD

Associate Professor, UC Department of Pediatrics

Phone: 513-636-0991

Fax: 513-636-3768

Email: Marie-Dominique.Filippi@cchmc.org

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Specialties

I am particularly interested in dissecting the molecular mechanism of hematopoietic cell migration, including neutrophils and hematopoietic stem cells in physiological settings. Migration is a critical function of hematopoietic cell in which actin cytoskeleton reorganization plays a central role. Because hematopoietic cells are utilized for the therapy of multiple blood diseases and neutrophils are responsible for maintaining an immunocompetence status, understanding the molecular mechanism of normal hematopoietic cell functions is of potential therapeutic importance. The small RHO GTPase family, members of the Ras superfamily, including Rac, RHO and CDC42, play key roles in regulating many of these functions. During my post-doc in the laboratory of Dr David Williams, we have demonstrated that two highly related proteins, Rac1 and Rac2, of the small Rho GTPase family, have distinct functions in the control of hematopoietic cell functions. In particular in neutrophils, we have shown that both Rac1 and Rac2 regulate cell migration but with distinct mechanism (Gu and Filippi et al, Science 2003) both in vitro and in vivo. In addition to this work, we have dissected the sequence/determinant specificity of Rac2 versus Rac1 functions in neutrophils and demonstrated that Rac2 controls its functions, at least in part, by distinct subcellular distributions of these GTPases (Tao et al, Blood 2002, Filippi et al, Nat Immunol 2004), highlighting one important mechanism controlling cellular functions.

My laboratory, in collaboration Dr. Yi Zheng, is now focused on determining the role of CDC42 and RhoA in neutrophil migration and in determining specifically the role of RhoA in hematopoietic stem cell migration and proliferation using gene targeted knock out mice for CDC42 and RhoA and their respective regulator CDC42GAP and 190RhoGAP. These studies will use in vitro and in vivo assays of cell migration as well as immunofluorescence microscopy to study cytoskeleton rearrangement associated with cell migration.

The long term goal of these studies is to identify new molecular targets of potential therapeutic importance.

Visit the Filippi Lab.

Education and Training

PharmD: University of Rene Descartes, Paris, France, 1998.

Residency: Hematopathology, University of Rene Descartes, Assistance public Hospital of Paris, Paris, France.

Certification: Hematopathology, 2001.

PhD: University of Denis Diderot, Paris, France, 2001.

Publications

View PubMed Publications

Grants

Regulation of Hematopoietic Stem Cell Self Renewal. Principal Investigator. National Institutes of Health. Aug 2010 - Aug 2012. #R21 HL 104458.

Regulation of Neutrophil Migration and Polarity. National Institutes of Health. Mar 2010 - Mar 2015. #R01 HL 090676.