The joint effort of the PIs for more than 10 years resulted in significant accomplishments in the scientific quality, infrastructure development, and education. The group was the first to propose and conduct clinical trials on autologous hematopoietic stem cell transplantation for the treatment of type 1 diabetes mellitus (Voltarelli et al. JAMA 2007; Couri et al. JAMA 2009). This study was made possible by the establishment of GMP-grade tissue culture and cryopreservation laboratories coordinated by Covas; analyses of cell transcriptome and proteome by Silva, Zago, and Greene; and clinical trials in the bone marrow transplant unit led by Voltarelli. The group also extensively collaborated in the study of mesenchymal stromal cells (Panepucci et al. Stem Cells 2007; Covas et al. Exp Hematol 2008; Saldanha-Araujo et al. Stem Cell Res 2011). Zago, Calado, Silva, and Covas worked jointly to identify the origins of these cells, as well as gene expression signatures and immunomodulatory properties. The Center is now the only one in the country able to provide mesenchymal stromal cells for clinical purposes and several clinical trials in the present proposal are based on this infrastructure. The investigation of acute promyelocytic leukemia as a model for cancer biology is an example of “bench-to-bedside” research established by the group (Figueiredo-Pontes et al. PLOS One 2011, Rego et al. Blood 2009, dos Santos et al. Leukemia 2011). We have developed new genetically-modified animal models for leukemia at a new animal care facility built specifically for this group of PIs for pre-clinical studies and involving the collaboration among Rego (animal models), Falcão (flow cytometry), and Greene (proteomics). Our group coordinates in Brazil The International Consortium on Acute Promyelocytic Leukemia (IC-APL), an initiative of the American Society of Hematology aiming to reduce the gap between developing and developed countries on the treatment outcome of patients with acute promyelocytic leukemia. This study involves researchers of our group (Rego, Silva, and Falcão) and other seven hematology centers across the country. The group worked together in the identification of molecular characteristics of other leukemia cells, such as the cancer-testis antigen expression in lymphoproliferative disorders (Proto-Siqueira et al. Leuk Res 2006; Figueiredo DL), which served as the basis for testing monoclonal antibodies for therapy. The interaction among Calado, Falcão, and Zago originated a pan-American effort (Brazil, US, and Canada) that established telomerase lesions as a risk factor for leukemia (Calado et al. PNAS 2009). The collaboration between Covas and Pereira resulted in the first Brazilian publication on induced pluripotent stem cells (Picanço-Castro et al. Stem Cell Dev 2011). In biotechnology, the group developed vectors and cellular systems for the production of the clotting factor IX, and the establishment of infrastructure for large-scale production for pre-clinical purposes. The collaboration between Covas and Meirelles has generated genetically modified calves harboring the human factor IX gene under the control of beta-lactoglobulin promoter (Monzani et al. submitted). On education, two major accomplishments should be highlighted. The creation of “Casa da Ciência” (House of Science) allowed the interaction of our scientists with more than 2,000 middle-school students and 150 teachers to learn about science and foster their future careers in science. The group jointly created the first professional Master program in biological sciences at the University of São Paulo as well as a new graduate program (MSc and PhD) in stem cells and oncology that will begin in 2012.
