Marcio Chaim Bajgelman
Marcio Chaim Bajgelman
Group Leader, LNBio – CNPEM
Coordinator of Viral Vector Laboratory
Phone: +55 19 3512-1104
The aim of our research is developing experimental approaches for cancer therapy, based on delivery of inhibitory molecules to tumor cells or boosting immune cells to eliminate tumors.
Exploration of molecular targets to inhibit regulatory T cells
Regulatory T cells (Treg) can suppress effector T cell proliferation and induce immunological tolerance. Clinical samples isolated from patients demonstrate that Treg infiltrate in the tumor site correlates with the progression of cancer. Literature data suggest that elimination of Treg cells enhance strategies for cancer treatment. In general, strategies for inhibition of Tregs can be grouped into depletion, blocking function or blocking traffic. The strategies are currently used are based on depletion using antibodies and chimerical proteins directed to the IL-2 receptor (CD25). These approaches have no specificity and may counteract antitumor immune response. In this project we are investigating the inactivation of molecular targets that are important for the immunosuppressive phenotype of Treg, using RNAi. The inhibition of molecular targets should inactivate suppressive phenotype of Treg and to potentiate antitumor immunity.
Development of targeting strategies to deliver therapeutic cassettes
The gene transfer of an expression cassette or RNAi may be used to induce a phenotypic change in target cells, associated with a therapeutic effect. One of the major challenges for the success of gene therapy is to develop vectors that have high efficiency and specificity to transduce a target cell, while minimizing the possibility of causing side effects.
Our group works on developing recombinant viral vectors based on retrovirus, lentivirus, adenovirus, and adeno-associated virus. These vectors are engineered to carry an expression cassette to a specific target cell. We can modify viral capsid to drive tropism and also to control virus expression trough chimerical promoters which allow a constitutive, inducible or tissue specific expression. Viral vectors have high transduction efficiency of primary cells. Retrovirus and lentivirus can be used to establish genetically modified cell lines, besides lentiviral vectors being used to generate transgenic animals.
In addition, we also develop a non-viral delivery system based on Chimerical RNA aptamers. These aptamers allow a specific delivery of RNAi molecules to target cells, via cell surface receptor. Aptamers have low immunogenicity and are a promising tool to deliver inhibitory molecules in vivo.
PhD in Biotechnology, Biotechnology program , University of Sao Paulo, 2006. Advisor: Dr. Bryan Eric Strauss. Title of Thesis: “Development of an inducible system for production of retroviral vectors encoding cytotoxic genes”.
PharmD, School of Pharmaceutical Sciences, specialization in Clinical Biochemistry, University of Sao Paulo, 2001
2009-2011 postdoctoral fellow, Sylvester Cancer Center, Miller School of Medicine, University of Miami. Laboratory of Dr. Eli Gilboa
2006-2009 postdoctoral fellow, Heart Institute, School of Medicine, University of Sao Paulo. Laboratory of Dr. Bryan Eric Strauss.
1. BAJGELMAN, M. C. ; COSTANZI-STRAUSS, E. C. ; STRAUSS, B. E. . Exploration of critical parameters for transient retrovirus production. Journal of Biotechnology, v. 103, p. 97-106, 2003.
2. STRAUSS, B. E. ; BAJGELMAN, M. C. ; COSTANZI-STRAUSS, E. C. . A novel gene transfer strategy that combines promoter and transgene activities for improved tumor cell inhibition.. Cancer Gene Therapy , v. 12, p. 935-946, 2005.
3. STRAUSS, B. E. ; Patrício, J.R. ; CARVALHO, A. C. ; BAJGELMAN, M. C. . A lentiviral vector with expression controlled by E2F-1: A potential tool for the study and treatment of proliferative diseases.. Biochemical and Biophysical Research Communications , v. 348, p. 1411-1418, 2006.
4. BAJGELMAN, M. C. ; STRAUSS, B. E. . The DU145 human prostate carcinoma cell line harbors a temperature-sensitive allele of p53.. The Prostate , v. 66, p. 1455-1462, 2006.
5. BAJGELMAN, M. C. ; STRAUSS, B. E. . Development of an adenoviral vector with robust expression driven by p53. Virology , v. 371, p. 8-13, 2008
6. BRESSAN, F. F. ; dos santos miranda, m. ; perecin, f. ; De Bem, T.H. ; Pereira, F.T. ; Russo-Carbolante, E.M. ; Alves, D. ; STRAUSS, B. E. ; BAJGELMAN, M. C. ; KRIEGER, J. E. ; Binelli, M. ; Meirelles, F.V. Improved production of genetically modified fetuses with homogeneous transgene expression after transgene integration site analysis and recloning in cattle. cell reprogramming , v. 13, p. 29-36, 2011.