Carmem Gottfried
A. Personal Statement I did MSc and PhD in Biochemistry and permanently joined the Department of Biochemistry as associate professor linked to the Postgraduate Program in Biological Sciences: Biochemistry in 2005. I have been working on autism research, employing a translational approach, related to both clinical and basic science since 2006. I coordinate the Art and Neuroscience Extension Project, producing books for children about neural cells. B. Positions and Honors 2019 – present - Founding member of the Autism Wellbeing And Research Development (AWARD) Initiative BR-CA-UK 2013 - 2014 - Director of Postgraduate Program in Neuroscience, Federal University of Rio Grande do Sul, Brazil 2009 - 2013 - Vice-Director of Postgraduate Program in Neuroscience, Federal University of Rio Grande do Sul, Brazil. 2009 - Honored professor - Graduates in Biomedical Sciences 2008 - Honored professor - Graduates in Biomedical Sciences 2007 - present - Steering committee of the Translational Research Group in Autism Spectrum Disorder, Clinical Hospital of Porto Alegre (HCPA), Federal University of Rio Grande do Sul, Brazil. 2005 - present - Associate Professor, Department of Biochemistry, Federal University of Rio Grande do Sul, Brazil 2005 - present- Fellow of productivity in Research by the National Council for Scientific and Technological Development (CNPq), Ministry of Science and Technology, Brazilian Government. https://www.inctnim.fiocruz.br/ 2005 - present - Head of the Research Group in Neuroglial Plasticity, Department of Biochemistry, Federal University of Rio Grande do Sul, Brazil. C. Contribution to Science 1. Preventive strategy in animal model of autism One of the main challenges in the study of ASD is the understanding of its etiology. Animal models have been a valuable approach to investigate the autism triggering. Through a prenatal approach in the rodent model of autism induced by VPA, we designed a strategy to prevent the triggering by pregnancy treatment with resveratrol. This approach has enabled us to understand trigger-induced molecular and metabolic alterations and which of these have been prevented by resveratrol. Fontes-Dutra, M., Santos-Terra, J., Deckmann, I., Schwingel, G.B., Nunes, G.D.-F., Hirsch, M., Bauer-Negrini, G., Riesgo, R., Bambini-Júnior, V., Hedin-Pereira, C., Gottfried, C., 2018. Resveratrol prevents cellular and behavioral sensory alterations in the animal model of autism induced by valproic acid. Front. Synaptic Neurosci. 10, 9. doi:10.3389/FNSYN.2018.00009 Bambini-Junior, V., Zanatta, G., Della Flora Nunes, G., Mueller de Melo, G., Michels, M., Fontes-Dutra, M., Nogueira Freire, V., Riesgo, R., Gottfried, C., 2014. Resveratrol prevents social deficits in animal model of autism induced by valproic acid. Neurosci. Lett. 583, 176–81. doi:10.1016/j.neulet.2014.09.039 Hirsch, M, Deckmann, I., Fontes-Dutra, M., Bauer-Negrini, G., Della-Flora Nunes, G., Nunes, W., Rabelo, B., Riesgo, R., Margis, R., Bambini-Junior, V., Gottfried, C., 2018. Behavioral alterations in autism model induced by valproic acid and translational analysis of circulating microRNA. Food Chem. Toxicol. 115, 336–343. doi:10.1016/j.fct.2018.02.061 2. Reversal of behavioral impairment in an animal model of autism Once diagnosed, the challenge is to find therapeutic strategies for the core of autism, considering the different degrees of severity. Usually treatments are centered on associated symptoms, such as aggressiveness, sleep disturbance, etc., and not on the central features, involving social and communication impairment. In this context, we are demonstrating different strategies, in both VPA animal model (Hirsch et al., 2020, Castro et al., 2017, Baronio et al., 2015) and patients (Castro et al., 2016): Hirsch, M., Deckmann, I., Santos-Terra, J., Staevie, G., Fontes-Dutra, M., Carello-Collar, G., Körbes-Rockenbach, M., Schwingel, G., Bauer-Negrini, G., Rabelo, B., Gonçalves, M., Corrêa-Velloso, J., Naaldijk, Y., Castillo, A. Schneider, T., Bambini-Junior, V., Ulrich, H., Gottfried, C., 2020. Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism. Neuropharmacology 167. doi:10.1016/j.neuropharm.2019.107930 Castro, K., Baronio, D., Perry, I., Riesgo, R., Gottfried, C., 2017. The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. Nutr. Neurosci. 20, 343–350. doi:10.1080/1028415X.2015.1133029 Castro, K., Faccioli, L., Baronio, D., Gottfried, C., Perry, I., Riesgo, R., 2016. Feeding behavior and dietary intake of male children and adolescents with autism spectrum disorder: A case-control study. Int. J. Dev. Neurosci. 53, 68–74. doi:10.1016/j.ijdevneu.2016.07.003 Baronio, D., Castro, K., Gonchoroski, T., de Melo, G, Nunes, G., Bambini-Junior, V., Gottfried, C., Riesgo, R., Melo, G., Nunes, G., Bambini-Junior, V., Gottfried, C., Riesgo, R., 2015. Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid. PLoS One 10, e0116363. doi:10.1371/journal.pone.0116363 3. Pharmacological strategies Pharmacological therapies for neurodevelopmental and psychiatric disorders are also a constant challenge, due to adverse effects and lack of selectivity. The results of our work are a first step using in silico quantum biochemical design as means to impact the discovery of new medicines to improve antipsychotics, such as risperidone and haloperidol (Zanatta et al., 2016, 2018): Zanatta, G., Della Flora Nunes, G., Bezerra, E, Da Costa, R, Martins, A., Caetano, E., Freire, V, Gottfried, C., 2016. Two Binding Geometries for Risperidone in Dopamine D3 Receptors: Insights on the Fast-Off Mechanism through Docking, Quantum Biochemistry, and Molecular Dynamics Simulations. ACS Chem. Neurosci. 7. doi:10.1021/acschemneuro.6b00074 Zanatta, G., Da Silva, M.B., Silva, J.J., Dos Santos, R.., Sales, F.., Gottfried, C., Caetano, Freire, VN., 2018. First-generation antipsychotic haloperidol: optical absorption measurement and structural, electronic, and optical properties of its anhydrous monoclinic crystal by first-principle approaches. New J. Chem. 42, 13629–13640. doi:10.1039/c8nj01548 In addition, we are also working with H3R antagonist ciproxifan (CPX) on reversing behavioral simptoms in the VPA animal model. we report that an acute dose of CPX is able to attenuate sociability deficits and stereotypies present in the VPA model of autism. Our findings have the potential to help the investigations of both the molecular underpinnings of ASD and of possible treatments to ameliorate the ASD symptomatology, although more research is still necessary to corroborate and expand this initial data. Baronio, D., Castro, K., Gonchoroski, T., de Melo, G.M., Nunes, G., Bambini-Junior, V., Gottfried, C., Riesgo, R., Mueller De Melo, G., Nunes, G.D.F., Bambini-Junior, V., Gottfried, C., Riesgo, R., 2015. Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid. PLoS One 10, e0116363. doi:10.1371/journal.pone.0116363 4. Technology and Innovation Software development: Along our research with analysis of miRNA library, we realized how difficult it is to find software that allows simultaneously a robust and less complicated analysis. Accordingly, we worked in an automated miRDB-search of microRNA targets/seeds in mRNA sequences. The script was developed by the PhD student Guilherme Bauer Negrini, under my supervision, to implement a Selenium WebDriver to automate the access to miRDB - MicroRNA Target Prediction and Functional Study Database and search for microRNAs targets/seeds present in the given mRNA sequences. https://github.com/gbnegrini/mirdb-custom-target-search Patent – privilege of innovation: Use of at least one stilbene polyphenol family and method for preventing the development of autism in a descendant mammal. Register number: BR1020120293820. https://lume.ufrgs.br/bitstream/handle/10183/107427/000946448.pdf?sequence=1&isAllowed=y