Aparecida Maria Fontes
Scientific and Technologic Researcher II,
Hemocentro Ribeirão Preto – HC-FMRP/USP
fontesam@hemocentro.fmrp.usp.br 

Education  

1984-1988 Graduated in Biologic Sciences, Faculty of Philosophy, Science and Letters of Ribeirao Preto (FFCLRP) – University of São Paulo, Brazil
1989-1993 Master Thesis in Cell Biology and Morphology, Medical School of Ribeirão Preto, University of São Paulo
1993-1996 PhD in Cell Biology and Morphology, Medical Scholl of Ribeirão Preto, University of São Paulo
1997-2001 Postdoctoral Research Fellow, Medical School at Case Western Reserve University, Cleveland, OH, USA

Research Interests  

Transcriptional mechanisms used by Hox genes in Cancer
Transcriptional mechanisms used by Hox genes in hematopoiesis and vascular development
Development of human cell lines harboring synthetic wild-type and mutant FVIIIΔB and cell therapy models for Hemophilia

Research Overview   Our research aims to elucidate the role of HOX genes and their transcriptional regulation in cancer progression and during development. HOX genes are transcription factors that have crucial roles in the earliest steps of embryogenesis, cell differentiation and are conserved in all animal phyla. In cancer, our focus is medulloblastoma that arises in cerebellum. Hox genes orchestrate the embryonic vertebrate hindbrain patterning during cerebellum development and might have a role in medulloblastoma progression. To investigate this, medulloblastoma cell lines and patient-derived cells will be molecularly characterized about HOX gene expression level and transcriptional mechanisms of their regulation. Also, we will perform in vitro and in vivo models to identify transcriptional mechanisms of HOX regulation during cancer progression. In development, we are studying blood and vascular cell formation. In the embryogenesis, it is known that blood and vascular cells derive from a common precursor cells, named hemangioblasts, which arise in the yolk sac and in the aorta-gonadal-mesonephros (AGM) mesenchyme. However, the early regulatory network of transcription factors that established the blood versus vascular fate has not been fully understood. We are interested to investigate the role of HOX genes which allow uncommitted cell becomes specified into blood cells or endothelial cells. Also, we are studying transcriptional mechanism regulation of HOX gene in this biological process. We will generate a human-specific cellular system to study early hemato-endothelial development in genetically modified human embryonic stem cells. One third interest is to develop human cell lines harboring synthetic wild-type and mutant FVIIIΔB and cell therapy models for Hemophilia A. For the latter, we will use endothelial or mesenchymal adult cells or endothelial-derived embryonic stem cells to compare the efficacy of these cells to deliver FVIII to a sufficient level and yield therapeutic effect using hemophilia A mice model.
Lab Staff  

Gene Transfer Group
Ricardo Bonfim-Silva, PhD Student/FAPESP
Lucas E. Botelho de Souza, Master Student/CNPq
Everton de B. Oliveira Costa, Master Student/CNPq
Daianne M. A. de Carvalho, CTC/FAPESP
Angelo Luis Caron, Scientific Initiation Student
Hudson Bezerra, Master Student

Molecular and Cell Biology Technician
Danielle Aparecida Magalhães 

Collaborators  

Gil Cunha de Santis, M.D., Ph.D.
Hemocentro de Ribeirão Preto-HC-FMRP/USP
Gerente Médico
gil@hemocentro.fmrp.usp.br

Edson Garcia Soares, M.D., Ph.D.
Faculdade de Medicina de Ribeirão Preto
Laboratório de Patologia
egsoares@fmrp.usp.br

Elisabeth de Fátima Pires Augusto, PhD
Instituto de Pesquisas Tecnológicas – IPT
Cidade Universitária – USP
Industrial Biotechnology Laboratory
eaugusto@ipt.br

Kuruvilla Joseph Abraham, Ph.D.
Faculdade de Medicina de Ribeirão Preto, USP
Professor Visitante do Exterior – CAPES
abraham@fmrp.usp.br

 

International Collaborators  

Gregory J. Riggins, M.D., Ph.D.
Professor of Urology and Preventive Medicine’
Director, Division of Neurosurgery Research
1550 Orleans Street/ Koch Building, Room 257
Johns Hopkins University – School of Medicine
Baltimore, MD 21231

Angelo A. Cardoso, M.D., Ph.D.
Ass. Professor Medicine, Medical and Molecular Genetics
I.U. Simon Cancer Center
980 W. Walnut Street, R3-C312
Indiana University – School of Medicine
Indianapolis, IN 46202

Graça D. Almeida-Porada, M.D., Ph.D.
Professor of Regenerative Medicine
Wake Forest Institute for Regenerative Medicine
391 Technology Way
Wake Forest University – School of Medicine
Winston-Salem, NC 27157-1083

Facilities Coordination   Animal Model Investigation (IVIS Lumina) 
Selected Publications  

1. DE CASTILHO-FERNANDES A, FONTES AM, ORELLANA MD, PALMA PVB, MELO FUF, FREITAS MCC, PICANÇO-CASTRO V, COVAS DT. (2011). Human hepatic stellate cell line (LX-2) exhibits characteristics of bone marrow-derived mesenchymal stem cells. Experimental and Mol. Pathol. 91:664-672.
2. FERNANDES AC, FONTES AM, ROSA NG, SWIECH K, PICANÇO-CASTRO V, FAÇA S AND COVAS DT. (2011). Stable and high-level production of recombinant Factor IX in human hepatic cell line. Biotech. and Applied Bioch. 58:243-249.
3. CUNHA NB, MURAD AM, RAMOS GL, MARANHÃO AQ, BRÍGIDO MM, ARAÚJO AC, LACORTE C, ARAGÃO FJ, COVAS DT, FONTES AM, VIANNA GR, RECH EL. (2011). Accumulation of functional recombinant human coagulation factor IX in transgenic soybean seeds. Transgenic Res. 20:841-855.
4. PRATA KL, ORELLANA MD, DE SANTIS GC, KASHIMA S, FONTES AM, CARRARA RCV, PALMA PVB, NEDER L AND COVAS DT. (2010). Effects of high dose chemotherapy on bone marrow multipotent mesenchymal stromal cells isolated from lymphoma patients. Exp. Hematol. 38:292-300.
5. da SILVA-MEIRELLES L, Fontes AM, COVAS DT AND CAPLAN AL (2009). Mechanisms involved in the therapeutic properties of Mesenchymal Stem Cells. Cytokine & Growth Factor Rev. 20:419-427.
6. PICANÇO-CASTRO V, FONTES AM, RUSSO-CARBOLANTE EMS AND COVAS DT. (2008). Lentiviral-mediated gene transfer a patent review. Expert Opin. Therap. Patents 18:525-539.
7. COVAS DT, PANEPUCCI RA, FONTES AM, SILVA JR WA, ORELLANA MD, FREITAS MCC, NEDER L, Santos ARD, PERES LC, JAMUR MC AND ZAGO MA. (2008). Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Exp. Hematol. 36: 642-654.
8. PICANÇO VP, FONTES AM, HEINZ S, TORSTEN T AND COVAS DT (2008). The chimeric cytokine Hyper-IL-6 enhances the efficiency of lentiviral gene transfer in hepatocytes both in vitro and in vivo. Biotechnology Letters 30: 215-220.
9. CARRARA RCV, ORELLANA MD, FONTES AM, PALMA PVB, KASHIMA S, MENDES MR, COUTINHO MA, VOLTARELLI JC AND COVAS DT. (2007). Mesenchymal stem cells from patients with chronic myeloid leukemia do not express BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant. Braz. J. Med. Biol. Res. 40: 57-67.
10. COVAS DT, OLIVEIRA FS, RODRIGUES ES, ABE-SANDES K, SILVA WA AND FONTES AM (2007). Knops blood group haplotypes among distinct Brazilian populations. Transfusion 47:147-153