Vesa M. Kaartinen Assistant Professor Developmental Biology, Pathology Keck School of Medicine The Saban Research Institute Childrens Hospital Los Angeles

Education:
BS 1984 Biochemistry - University of Kuopio, Finland
MSc 1986 Biochemistry - Univeristy of Kuopio, Finland
PhD 1991 Biochemistry - University of Kuopio, Finland

Postdoctoral Research Fellowship:
1992 - 1996 University of Southern California, School of Medicine

Started at USC: 1996

Research Topics: Developmental Biology, Cancer Cell Biology

Research Description

The main focus in my laboratory is to determine the developmental role of selected biologically significant proteins in vivo using genetically manipulated mice. Using gene targeting in embryonic stem cells we have generated TGFß3-deficient mice, which suffer from bilateral clefting of the secondary palate and abnormal pulmonary development (Kaartinen et al., 1995). Our subsequent studies have revealed novel aspects of the role of TGFß3 during glucocorticoid-induced pulmonary maturation just before the birth.

Moreover, we have shown that medial edge epithelial cells of the TGFß3-/- palatal shelves fail to transdifferentiate to mesenchymal cells and that this defect is associated with defective degradation of the basement membrane. Currently my laboratory focuses on the role of small GTPases, TGFß-signaling molecules and metalloproteinases in epithelial-mesenchymal interactions, particularly in palatogenesis (Blavier et al., 2001). During recent months we have effectively utilized the so called Cre-loxP strategy, which allows both inducible and tissue specific inactivation of gene of interest in the specific target tissue or organ (Kaartinen and Nagy,2001). Since cleft palate is among the most common congenital birth defects in humans, we feel that these studies are of critical importance when determining the exact molecular mechanisms of TGFß3-induced palatal fusion.

My laboratory is also studying the role of TGF(3 and the small GTPases in the development of invasive mammary carcinoma. To further evaluate the biological role of TGFßs, we have shown that they are differentially expressed during mammary gland involution(Faure et al., 2000). Recently, we were able to show that Abr and Bcr RacGAPs display a critical role in astroglial functions(Kaartinen et al., 2001). Parallel with these studies I have generated a mouse model for the most common lysosomal storage disorder of glycoprotein degradation, aspartylglycosaminuria (AGU)(Kaartinen et al., 1996). Our detailed analyses have revealed that these mice possess all the hallmarks of the human AGU. Therefore this mouse strain can be used as a model for the human disease. Recently, with the help of these mice, we have evaluated the efficacy of an enzyme replacement therapy to treat AGU(Dunder et al., 2000).