Yuet W. Kan, M.D.
	Experimental gene and cell therapy in heart and blood diseases
	Email: yw.kan@ucsf.edu
Selected Publications | Complete Publications

Our laboratory has been interested for some years in studying the molecular mechanisms in genetic diseases of the blood. While our previous research has been focused on the diagnosis and pathogenesis of diseases, our current work is directed towards the experimental treatment of 2 groups of diseases by gene and cell therapy.

Coronary Heart Diseases: We are investigating the use of adeno-associated viral (AAV) vector for gene therapy, and bone marrow mesenchymal stem cells (MSC) for the treatment of ischemic heart disease. Using a mouse model in which the coronary artery is tied, angiogenic factors including vascular endothelial growth factor (VEGF) and angiopoietins, under the control of cardiac specific promoter and hypoxia responsive element (HRE) delivered into the myocardium could reduce the size of infarcts and improve cardiac functions. To prepare for possible future human applications, the efficacy of these vectors is being tested in a porcine model. MSC delivered into the heart have been reported to improve cardiac functions in patients with coronary heart disease. We are investigating the properties of MSC and the effect of their delivery in vivo.

Sickle cell anemia and thalassemia: Our laboratory has previously made mouse models of sickle cell anemia and thalassemia. Because the anemia in ? thalassemia is manifested in intrauterine life, the mouse offers a good model to test intra-uterine gene therapy. We are using a lentiviral vector to deliver the ?-globin gene into the hematopoietic cells of the fetal mouse liver.

Embryonic stem (ES) cell therapy is being tested in the sickle cell anemia mouse. We have derived embryonic stem cells from these mice carrying the human sickle cell anemia genotype. By means of homologous recombination with a normal ?-globin gene, the sickle mutation in one allele has been corrected to the normal gene. The ES cells are being differentiated into hematopoietic stem cells for transplantation in order to treat the sickle cell anemia mouse. As the approach that we use can correct the human ?-globin gene mutations in ? thalassemia as well, we are exploring its application in this hereditary disease as well.

Selected Publications

Chang JC, Ye L, Kan YW. Correction of the sickle cell mutation in embryonic stem cell. Proc Natl Acad Sci U S A. 103: 1036-40, 2006.

Su H, Huang Y, Takagawa J, Barcena A, Arakawa-Hoyt J, Ye J, Grossman W, Kan YW. AAV serotype-1 mediates early onset of gene expression in mouse hearts and results in better therapeutic effect. Gene Ther. 2006 Nov;13(21):1495-502.

Information last updated April 2007