CEGH-CEL - Human Genome and Stem Cell Research Center

• Grant number: 13/08028-1
• Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• Duration: July 01, 2013 - June 30, 2024
• Field of knowledge: Biological Sciences - Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Mayana Zatz
• Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo, SP, Brazil
• Co-Principal Investigators: Angela Maria Vianna Morgante ; Carla Rosenberg ; Celia Priszkulnik Koiffmann ; Eliana Maria Beluzzo Dessen ; Ésper Abrão Cavalheiro ; Maria Rita dos Santos e Passos Bueno ; Mariz Vainzof ; Merari de Fátima Ramires Ferrari ; Oswaldo Keith Okamoto ; Peter Lees Pearson ; Regina Célia Mingroni Netto
• Assoc. researchers: Ana Cristina Victorino Krepischi ; Angela Maria Vianna Morgante ; Carlos Frederico Martins Menck ; Celia Priszkulnik Koiffmann ; David Schlesinger ; Débora Romeo Bertola ; Edson Amaro Junior ; Fernando Kok ; Joao Paulo Fumio Whitaker Kitajima ; Jorge Elias Kalil Filho ; Luciana Amaral Haddad ; Luis Eduardo Soares Netto ; Maria Dulcetti Vibranovski ; Maria Lúcia Lebrão ; Merari de Fátima Ramires Ferrari ; Miguel Mitne Neto ; Nivaldo Alonso ; Peter Lees Pearson ; Rita de Cássia Mingroni Pavanello ; Tatiana Teixeira Torres ; Valdemir Melechco Carvalho ; Venancio Avancini Ferreira Alves ; Verônica Porto Carreiro de Vasconcellos Coelho ; Yeda Aparecida de Oliveira Duarte
• Associated grant(s): 16/50021-2 - Cancer stem cell interactome mapping, AP.R; 14/20796-7 - Synaptopathies in neurodevelopmental disorders: SHANK mutations as a window into synaptic function, AR.EXT
• Associated scholarship(s): 18/20373-0 - Caracterization of the proteic interactoma of the pluripotency factor L1TD1 in central nervous system tumour stem cells and neural stem cells, BP.IC; 16/14517-3 - Search for "protective" modifying variants/mechanisms in asymptomatic or very mildly affected individuals with pathogenic mutation in SPAST gene, BP.PD; 17/16283-2 - Development of tissue bioengineering techniques for the functional reconstruction of ex vivo iPSC cell livers, BP.PD; + associated scholarships 17/11430-7 - Interaction of genetic and epigenetic factors in response to inflammation for the predisposition to cleft lip-palate, BP.PD; 17/05824-2 - Investigation of parents de novo risk variants in Autism Spectrum Disorder (ASD), BP.DR; 16/23648-4 - Investigation of the etiological relevance of novel candidate genes to orofacial clefts, BP.PD; 16/17392-7 - Association study of rare variants in candidate genes for orofacial clefts in the brazilian population, BP.DR; 15/18914-4 - Study of the regenerative potential of satellite cells in centronuclear myopathy and myogenic capacity of its released microvesicles, BP.DR; 15/19435-2 - Therapeutic analysis of human immunoglobulin g in a mouse model for Duchenne Muscular Dystrophy, BP.IC; 15/14821-1 - Development of functional hepatic by-pass using iPSCs derived cells, BP.DR; 15/18130-3 - Analysis of the autophagic pathway in the dystrophic muscle, BP.MS; 14/23043-0 - Identification of miRNAs with critical function in neurogenesis and oncogenesis, BP.PD; 15/08563-0 - DYRK1A regulation by microRNAs in cultured neurons from the hippocampus of mice models of human trisomy 21 and its relation with Alzheimer's Disease, BP.IC; 15/06786-1 - Stress of endoplasmic reticulum and expression of VAPB and Rab1 in cultured motor neurons from a mouse model of Amyotrophic Lateral Sclerosis, BP.IC; 14/24541-3 - Use of GFP fusions to analyze the mechanisms of toxicity of human VAPB expressed in Saccharomyces cerevisiae, BP.IC; 14/17132-0 - Use of Next Generation Sequencing to study karyotypes with different number of X chromosome, BP.PD; 14/13056-7 - Characterization of INDELs and small CNVs in patients with autism spectrum disorder, BP.MS; 14/10519-6 - HIPPO signaling pathway and asymmetric division of cancer stem cells derived from human medulloblastoma, BP.PD; 13/14996-0 - Detection of fetal genetic disorders through non-invasive prenatal testing using next-generation sequencing, BP.DR; 12/09950-9 - Evolution of HLA genes: population differentiation and signatures of recent selection in native and admixed populations from Brazil, BP.PD - associated scholarships

Abstract

The Human Genome Research Center (HGRC-CEPID I) was initiated in 2000 with the main goal of increasing our basic knowledge and diagnosis of prevalent genetic diseases in the Brazilian population. The HGRC concentrated largely on Mendelian disorders, mainly neuromuscular, craniofacial, and mental disability. The scope was expanded in 2005 by incorporating stem-cell research, both as a tool to understand gene expression and differentiation in genetic disorders and to evaluate its potential in disease therapy. Our research has allowed us to address questions on the genetic regulation of particular complex disorders such as autism and various neurodegenerative diseases. However, the unanticipated complexity of the transcriptional mechanisms regulating gene expression in humans that emerged from the Human Genome Project, and the modest advances in improving the effectiveness of genetic health care have opened new fields of investigation. In this CEPID 11 application, we have expanded the scientific breadth to include ageing and degeneration and how factors such as genome instability contribute to the aging process; the role of imprinting mechanisms on disease manifestation; which factors determine differences in the rate of brain degeneration between individuals, which constitutes a rapidly increasing health care burdon as the average life-span of the world population rises; what determines phenotypic variability between individuals carrying the same mutation. To address these questions we will use up to date approaches, particularly the use of second generation sequencing and sophisticated cell sorting, incorporate a much broader base of scientific expertise, optimize inter-group synergy as well as national and international research collaboration. The plan also contributes to translational medicine mainly in the application of stem-cells in preclinical studies and therapeutic trials for particular genetic disorders. The great number of patients with different genetic disorders that have been ascertained and registered in our center, the largest one in Latin America, and the ethnic variability of the Brazilian population provides an extremely rich foundation for the proposed studies. We are positive that the knowledge gained from CEPID 11 will have an important impact on genetic health care in Brazil. However, such an ambitious and integrated program can only be expedited by the flexibility and long term security offered by CEPID funding. (AU)

Filed patent(s) as a result of this research project