Research >> Globin Gene Gisorders and Iron Haemostasis

Globin Disorders

This has been an area of major interest over the past 15 years with work on molecular genetics of thalassemia and haemoglobin E in India. This work has lead to 2 PhDs with significant contributions to the knowledge in this field particularly from India. Further work continues on the understanding of the regulation of haemoglobin synthesis in the haematopoietic stem cells.

Mechanism of Globin gene regulation

During human development, three different types of hemoglobins are produced; embryonic, fetal and adult hemoglobins. We are trying to understand the roles of transcription factors and epigenetics in developmental stage specific regulation of globin genes. We are also trying to understand the regulatory sequences in the globin clusters that help in stage specific expression of these genes. We are carrying out ex-vivo differentiation of haematopoietic stem cells to erythroid lineage and studying interaction of proteins with the DNA sequences using chromatin immunoprecipitation followed by microarray (ChIP-chip) to understand the roles of transcription factors and epigenetic changes in the regulation of globin genes.

Transcriptional and translational process of the βE gene

Our work is to explore the genetic basis of phenotypic heterogeneity seen in haemoglobin E syndromes. We analyzed different genetic parameters which can influence the phenotype of HbE syndromes. We have identified novel mutations in HbE-β thalassaemia patients, new haplotypes of βE and were able to explain the genetic basis of jaundice in homozygous HbE. We have also identified that haemoglobin E levels play an important role in determining the total haemoglobin levels and act as a major determinant of disease severity. We are now analyzing factors at the transcriptional and translational level that influence HbE production in an exvivo model of erythropoiesis.

Ongoing Research Projects

• Project 1: Molecular mechanisms of human globin gene regulation- funded by DBT, India, 2009-2014. PI: Shaji R.V
• Project 2: Transcriptional and translational processes of βE gene- funded by DBT, India, 2009-2012. PI: Eunice Sindhuvi Edison

Iron Homeostasis

Eunice Sindhuvi Edison, Ph.D.

This is an area that is recently gaining interest again. We are looking for genetic changes in genes involved in different pathways of iron metabolism in patients with iron deficiency anemia (IDA), Iron refractory IDA (IRIDA) and transfusion dependant b thalassaemia patients with inappropriate iron overload. We are also looking at expression of iron regulatory genes during different stages of erythropoiesis.

Ongoing Research Projects:

• Project I: Molecular and Functional Evaluation of Genes Involved In Iron Absorption, Transport and Storage in the Context of Iron Deficiency- funded by DBT, India, 2009-2012. Principal Investigator: Eunice Sindhuvi Edison
• Project II: Are Polymorphisms In Iron Regulatory Genes Responsible For Phenotypic Differences In Iron Metabolism? - funded by DBT, India, 2010-2013. Principal Investigator: Eunice Sindhuvi Edison

Faculties involved

• Eunice Sindhuvi Edison, Ph.D.
• Shaji R.V., Ph.D.