The Cezar Laboratory
Faculty > Gabriela G. Cezar
Gabriela G. Cezar
Assistant Professor, Animal Sciences, Human Oncology
ggcezar@wisc.edu
Organ System/Disease Focus
Neurodevelopmental disorders, cancer
Aligned Research Focus
Stem cells in drug discovery and toxicology, metabolomics of human embryonic stem cells
Research Description
There are few sentinel biomarkers for early diagnosis of neurodevelopmental disorders. Our laboratory seeks to identify biochemical pathways and translational biomarkers that are altered by known disruptors of human development (valproate, alcohol), using metabolomics of hES cells and neural precursors derived from hES cells. This approach offers a unique advantage over other models since it employs cells derived directly from human embryos. Moreover, in addition to elucidating mechanisms of anti-epileptic and alcohol activity during early human development, the biomarkers discovered in hES cells are applicable to preclinical safety evaluation of pharmaceutical compounds on human development.
Another goal of our research is to examine the contribution of biochemical pathways identified by metabolomics on human neurogenesis, with special emphasis upon serotonergic (5HT, serotonin) neurons. Serotonergic development is disrupted by prenatal exposure to exogenous agents, and likely contributes to the cognitive dysfunction that typifies neurodevelopmental disorders. The effects of biochemical pathways of valproate-injury on human neurogenesis are determined by modulation of target pathways (detected by metabolomics) followed by differentiation of hES cells into neural precursors and serotonergic neurons. Our metabolomics approach is conducted in parallel to in silico analysis, in order to reveal candidate biological networks for the onset of neurodevelopmental disorders.
Selected References
Cezar GG, Quam JA, Smith AM, Guilherme J, Rosa M, Piekarczyk MS, Brown JF, Gage FH, Muotri AR. Identification of small molecules from human embryonic stem cells using metabolomics. Stem Cells Dev. In press.
Cezar GG. Can human embryonic stem cells contribute to the discovery of safer and more effective drugs? Curr Opin Chem Biol. Aug;11(4):405-9. 2007.
Chaudhary KW, Barrezueta NX, Bauchmann MB, Milici AJ, Beckius G, Stedman DB, Hambor JE, Blake WL, McNeish JD, Bahinski A, Cezar GG. Embryonic stem cells in predictive cardiotoxicity: laser capture microscopy enables assay development. Toxicol Sci. Mar;90(1):149-58. 2006.
Davila JC, Cezar GG, Thiede M, Strom S, Miki T, Trosko J. Use and application of stem cells in toxicology. Toxicol Sci. Jun;79(2):214-23. Epub 2004 Mar 10. 2004.