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Immunophenotypic characterization of stem-cells and hematopoietic progenitors compartments in patients with telomeropathies

Grant number: 21/01462-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2021
Effective date (End): April 30, 2022
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Rodrigo do Tocantins Calado de Saloma Rodrigues
Grantee:Flávio Augusto Tárcia Bicalho
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/08135-2 - CTC - Center for Cell-Based Therapy, AP.CEPID


Telomeres are repetitive structures of nucleotides and regulatory proteins located at the ends of linear chromosomes whose function is the maintenance of genomic integrity. Critically short telomeres induce disruption of cell proliferation, senescence or apoptosis. In cells with high proliferative demand, the telomeric length is maintained by the enzymatic complex of the telomerase, which catalyzes the addition of hexanucleotide DNA sequences at the 3 'telomeric end, using a constitutive RNA template. In telomeropathies, mutations that affect telomeric biology lead to poor cell regeneration, most often affecting the bone marrow, but also skin, lungs and liver, in addition to a greater predisposition to the development of some types of cancer.In the bone marrow, the abnormal wear of the telomeres causes the exhaustion of hematopoietic stem cells (HSCs), however, it is not well understood how the different populations of HSCs, multipotent parents and other blood cell precursors are particularly affected in telomeropathies. Our study, therefore, seeks to clarify the hematopoietic subpopulations most affected in these diseases, determining immunophenotypic panels by flow cytometry of CD34 + cells that populate the bone marrow of these patients. The results of the proposed work will deepen the knowledge about these rare diseases and unveil the bases for the future development of new more targeted and effective therapeutic options, such as autologous transplants and gene therapy.

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