Thalassemia is the most common genetic disorders in Thailand and worldwide. In the past several years, works from Thalassemia Research Center have defined the frequencies of different thalassemia genes, their molecular genetic nature, disease burdens, clinical manifestation and management. Thalassemia research covers the study from the clinical to the molecular levels, which is expanded in depth and scope. This information, including results of pathophysiologic studies, has been applied for better management of the patients and establishment of the prevention and control program of the disease. However, some clinical presentations still required more research for clarification. Therefore the research goals are

1. To understand the genotype-phenotype interaction in b-thalassemia/HbE. Substantial evidence suggests the involvement of additional factors that can modify clinical presentation amongst patients with similar b-thalassemia genotypes. A genome-wide search for genetic polymorphisms associated with disease severity revealed significant single nucleotide polymorphisms (SNPs) that may involve in disease heterogeneity. Functional studies for candidate genes are being explored including those involve in Hb F regulation, proteolysis and molecular mechanism of erythropoiesis and apoptosis.

2. To study the molecular mechanism of erythropoiesis and apoptosis in thalassemia. The thalassemias are characterized by the absence or reduced synthesis of one of the globin subunit of hemoglobin molecule. Thus the main pathophysiologic feature of thalassemia is the accumulation of unpaired globin chains in erythrocyte precursors and red blood cells. This accumulation alters cell membrane function and results in early cell destruction and ineffective erythropoiesis, leading to chronic anemia. A number of experiments including thalassemic mouse model, cultures of erythroid progenitors, and the role of microRNA have been established to understand molecular mechanisms of erythropoiesis and apoptosis.

3. To study the novel treatments by gene therapy and drugs that will enhance hemoglobin F synthesis for improving the patient’s quality of life. This study includes the use of antisense DNA and siRNAs in transgenic mice and primary erythroid cells.