Andre Luis Berteli Ambrosio

Andre LB Ambrosio, PhD

 

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Phone: +55 19 3512.1267

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RESEARCH INTERESTS

In order to sustain an inherently proliferative phenotype, cancer cells are in constant process of adaptation to the types and levels of available nutrients in the cellular microenvironment they inhabit. It is now known that the ability to metabolically adapt is primarily associated with activation of oncogenes or loss of tumor suppressors, which in turn result in selection by overexpression or isoforms of proteins that once were tightly regulated in normal cells. For instance, in contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, even under normoxia, a phenomenon termed ” Warburg effect”. The amino acid glutamine and sugar glucose are two of the most important and versatile nutrients in this context. Both serve as the main sources of carbon skeletons (for nucleotide synthesis, amino acids and lipids), generation energy in the form of ATP and recycling of reducing agents, such as NADPH, all essential to the process of growth, biomass doubling and subsequent cell division.

In this context, our major research in progress at our lab helps elucidating the basic structural, molecular and cellular mechanisms involved in the metabolic adaptation process of cancer cells to the microenvironment, using different tools such as x-ray crystallography (with access to the two macromolecular crystallography beamlines at LNLS), protein biochemistry and biophysics, computational approaches and more. Complementary, we established a close,  multidisciplinary collaboration with the lab of Dr. Sandra Dias, also at LNBio, aiming to combine cell culture models, an extensive array of both in vivo and in vitro assays, fluorescence microscopy, immunoprecipitation and blotting, in order to validate our hypothesis at all levels.

CURRENT PROJECTS

Ongoing projects aim to examine, from the structural, biochemical and biophysical standpoints, key components to maintaining high demands of biosynthetic and bioenergetic characteristics of cancer cells. Among those, we currently research on the glutaminases, the HIF-1 and MondoA transcription factors and the recently indentified mitochondrial pyruvate carrier.

 

SELECTED PUBLICATIONS

  1. Cassago A, Ferreira APS, Ferreira IM, Fornezari C, Gomes ER, Greene KS, Pereira HM, Garratt RC, Dias SMG and AMBROSIO ALB (2012) Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism. Proceedings of the National Academy of Sciences of the United States of America, 109, 1092 – 1097
  2. Wang JB, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, AMBROSIO ALB, Dias SMG, Dang CV and Cerione RA (2010) Targeting Mitochondrial Glutaminase Activity Inhibits Oncogenic Transformation. Cancer Cell, 18, 207 – 219
  3. AMBROSIO ALB, Dias SMG, Polikarpov I, Zurier RB, Burstein SH and Garratt RC (2007) Ajulemic Acid, a Synthetic Nonpsychoactive Cannabinoid Acid, Bound to the Ligand Binding Domain of the Human Peroxisome Proliferator-activated Receptor γ. Journal of Biological Chemistry 282, 18625 – 18633
  4. AMBROSIO ALB, Nonato MC, Selistre-de-Araujo H, Arni R, Ward RJ, Ownby CL, Souza DH and Garratt RC (2005) A molecular mechanism for Lys49-phospholipase A2 activity based on ligand-induced conformational change. Journal of Biological Chemistry 280, 7326 – 7335
  5. Cherepanov P, AMBROSIO ALB, Rahman S, Ellenberger T and Engelman A (2005) Structural basis for the recognition between HIV-1 integrase and transcriptional coactivator p75. Proceedings of the National Academy of Sciences of the United States of America, 102, 17308 – 17313

 

EDUCATION

May 2003 – May 2006

PhD in Biomolecular Physics
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP – Brazil

Harvard Medical School, Harvard University, Boston, MA – USA

Advisor: Richard Charles Garratt, PhD (USP) and Thomas Ellenberger, PhD (HMS)

Thesis title: “Determinante estruturais da interação entre PPARgama e o acido ajulêmico e bases do reconhecimento molecular entre HIV- 1 Integrase e o coativador transcricional p75”

Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

 

March 2001 – March/2003

MSc in Biomolecular Physics
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP – Brazil

Advisor: Richard Charles Garratt, PhD (USP)

Dissertation title: “Estudo da interação entre ácidos graxos e LYS49-fosfolipases A2 por difração de raios X e ressonância magnética nuclear”

Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

 

February/1997 – December/2000

Bachelor’s Degree in Physics

Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, SP – Brazil
PAST POSITIONS

 

January/2007 – July/2009

Postdoctoral fellow

College of Veterinary Medicine, Cornell University, Ithaca, NY – USA

Supervisor: Richard A Cerione, PhD

Funded by National Institutes of Health (NIH)