Marco A. Zago
Full Professor of Hematology, FMRP/USP
|Education||1965-1970 Graduated in Medicine, Medical School of Ribeirão Preto, University of São Paulo, FMRP-USP, Brazil. |
1971-1973 Master in Clinical Medicine, Medical School of Ribeirão Preto, University of São Paulo, FMRP-USP, Brazil.
1973-1975 PhD in Clinical Medicine, Medical School of Ribeirão Preto, University of São Paulo, FMRP-USP, Brazil.
1976-1977 Postdoctoral Research Fellow, Oxford University
1981 Full Professor, Medical School of Ribeirão Preto, University of São Paulo, FMRP-USP, Brazil
|Research Interests||Somatic and Pluripotent Stem Cells |
Cancer and Leukemia
microRNA and Transcription Factors
|Research Overview||In the last few years, we have addressed the characterization of somatic stem cells, including Mesenchymal Stem Cells (MSC) and Hematopoietic Stem Cells (HSC) from different sources, to study the molecular basis of their specific biological characteristics, as well as to provide evidence for their distribution and in vivo role. In fact, we have helped to establish the concept that MSCs occupy a perivascular niche throughout the body, closely resembling pericytes, providing a cell repository for tissue repair and also playing important roles in the maintenance of peripheral immunehomeostasis. In that sense, we provided evidence of a new immunomodulatory mechanism exerted by MSC in response to inflammatory stimuli derived from activated T lymphocytes (Saldanha-Araujo et.al. 2011). Moreover, our results points to a role of MSCs in the modulation of NF-kB signaling in activated T lymphocytes, switching from a canonical pro-inflammatory to a non-canonical immunoregulatory role (Saldanha-Araujo et.al. 2011b). We have also provided evidence for the role of non-canonical NF-kB signaling in the characteristic molecular features of HSC derived from Umbilical Cord Blood (UCB), as compared to Bone Marrow (BM). |
We are currently starting to address the molecular mechanisms by which MSC become activated to exert their immunomodulatory properties, upon treatment with pro-inflammatory stimuli (a mechanism generally referred as MSC “licensing” or “conditioning”). Finally, we are currently using synthetic pre-miRs and anti-miRs to explore the roles of microRNAs in the regulation of distinct stem cell characteristics (including pluripotency, differentiation, self-renewal, among others), and to identify functionally-relevant microRNA targets (trough coupled microarray profiling).
|Lab Staff|| |
Molecular Biology Technicians
Vanderson Rocha, PhD, MD (Hosp. Sírio Libanês, SP).
Felipe Saldanha Araujo, PhD (UNB, Brasília-DF).
Francisco de Paula Careta, PhD (UFES, -ES).
|International Collaborators|| |
|Facilities Coordination||Agilent 48-slides auto-loader High-Density Microarray Scanner and Axon GenePix 4000B (Molecular Devices).|
|Selected Publications||1. Saldanha-Araujo F., Haddad R., Malmegrim de Farias K.C., Alves Souza A.D., Palma P.V., Araujo A.G., Orellana M.D., Voltarelli J.C., Covas D.T., Zago M.A., Panepucci RA Mesenchymal stem cells promote the sustained expression of CD69 on activated T-lymphocytes: roles of canonical and non-canonical NF-kappaB signaling. Journal of cellular and molecular medicine. 2011a Jul 21. |
2. Saldanha-Araujo F., Ferreira F.I., Palma P.V., Araujo A.G., Queiroz R.H., Covas D.T., Zago M.A., Panepucci RA Mesenchymal stromal cells up-regulate CD39 and increase adenosine production to suppress activated T-lymphocytes. Stem cell research. 2011b Jul;7(1):66-74.
3. Picanco-Castro V., Russo-Carbolante E., Reis L.C., Fraga A.M., de Magalhaes D.A., Orellana M.D., Panepucci RA, Pereira L.V., Covas D.T. Pluripotent reprogramming of fibroblasts by lentiviral mediated insertion of SOX2, C-MYC, and TCL-1A. Stem cells and development. 2011 Jan;20(1):169-80.
4. De Molfetta G.A., Luciola Zanette D., Alexandre Panepucci R., Dos Santos A.R., da Silva W.A., Jr., Antonio Zago M. Role of NFKB2 on the early myeloid differentiation of CD34+ hematopoietic stem/progenitor cells. Differentiation; research in biological diversity. 2010 Nov-Dec;80(4-5):195-203.
5. Panepucci RA, Oliveira L.H., Zanette D.L., Viu Carrara Rde C., Araujo A.G., Orellana M.D., Bonini de Palma P.V., Menezes C.C., Covas D.T., Zago M.A. Increased levels of NOTCH1, NF-kappaB, and other interconnected transcription factors characterize primitive sets of hematopoietic stem cells. Stem cells and development. 2010 Mar;19(3):321-32.
6. Covas D.T., Panepucci RA, Fontes A.M., Silva W.A., Jr., Orellana M.D., Freitas M.C., Neder L., Santos A.R., Peres L.C., Jamur M.C., Zago M.A. Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Experimental hematology. 2008 May;36(5):642-54.
7. Proto-Siqueira R., Panepucci RA, Careta F.P., Lee A., Clear A., Morris K., Owen C., Rizzatti E.G., Silva W.A., Jr., Falcao R.P., Zago M.A., Gribben J.G. SAGE analysis demonstrates increased expression of TOSO contributing to Fas-mediated resistance in CLL. Blood. 2008 Jul 15;112(2):394-7.
8. Panepucci RA, Calado R.T., Rocha V., Proto-Siqueira R., Silva W.A., Jr., Zago M.A. Higher expression of transcription targets and components of the nuclear factor-kappaB pathway is a distinctive feature of umbilical cord blood CD34+ precursors. Stem Cells. 2007 Jan;25(1):189-96.
9. Proto-Siqueira R., Figueiredo-Pontes L.L., Panepucci RA, Garcia A.B., Rizzatti E.G., Nascimento F.M., Ishikawa H.C., Larson R.E., Falcao R.P., Simpson A.J., Gout I., Filonenko V., Rego E.M., Zago M.A. PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma. Leukemia research. 2006 Nov;30(11):1333-9.
10. Rizzatti E.G., Falcao R.P., Panepucci RA, Proto-Siqueira R., Anselmo-Lima W.T., Okamoto O.K., Zago M.A. Gene expression profiling of mantle cell lymphoma cells reveals aberrant expression of genes from the PI3K-AKT, WNT and TGFbeta signalling pathways. British journal of haematology. 2005 Aug;130(4):516-26.
11. Panepucci RA, Siufi J.L., Silva W.A., Jr., Proto-Siquiera R., Neder L., Orellana M., Rocha V., Covas D.T., Zago M.A. Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells. 2004;22(7):1263-78.
12. Silva W.A., Jr., Covas D.T., Panepucci RA, Proto-Siqueira R., Siufi J.L., Zanette D.L., Santos A.R., Zago M.A. The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells. 2003;21(6):661-9.