Protein and globin gene after the inhibition of Phosphatidylinositol-phosphate kinase-II-a (PIPKIIa)

• Grant number: 22/15058-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: March 31, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Susan Elisabeth Domingues Costa Jorge
• Grantee: José Octávio Gonçalves
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities, AP.TEM

Abstract

Understanding the regulatory mechanisms of hemoglobin (Hb) genes, in addition tothe widely known regulatory factors, has been the subject of extensive studies inrecent decades, not only for providing in-depth understanding of the regulation ofgene expression, but also for demonstrating potential targets for the reactivation offetal Hb (HbF) - silenced after birth - and of interest for the clinical management ofpatients with severe hemoglobinopathies. In a series of unpublished studies carriedout in our laboratory, evidence has pointed out the possible participation of theenzyme phosphatidylinositol-phosphate kinase-II-alpha kinase (PIPKIIa) in the processof erythropoiesis, regulation of hemoglobin genes and possible reactivation of HbF.Although this enzyme is present in abundance in erythrocytes, the real function itperforms there is not completely understood. Thus, the study of this protein, as well asother proteins of the same enzyme family, in addition to providing a betterunderstanding of its functions in erythroid cells, can add to the range of regulatoryproteins of globin genes and a possible pharmacological target for the treatment ofhemoglobinopathies. To achieve these purposes, immortalized erythroleukemic cellsK562 and KU812 will be treated with specific pharmacological inhibitors of the enzymePIPKII± and other enzymes of this subfamily and the gene expression and proteinsynthesis of globins will be measured. It is expected that the data from this study canmake significant discoveries about a new and complex regulatory mechanism for theproduction of Hb. This proposal is part of the PhD Project of Danaê Malimpensa,whichs aims to investigate the role of PIPKins in CD34+ progenitor cells.