Dr. Hans G. Richter Becerra

Investigación FAME UACh

  • Información Académica:

    • 1994: Licenciado en Bioquímica. Escuela de Bioquímica, Universidad Austral de Chile. Valdivia, Chile.
    • 2001: Doctor en Ciencias, Mención Biología Celular y Molecular. Escuela de Graduados. Facultad de Ciencias, Universidad Austral de Chile. Valdivia, Chile.
    • 2001-2003: Becado de postdoctorado. Grupo de investigación liderado por la Dra. María J. Serón-Ferré. Unidad de Reproducción y Desarrollo, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
    • 2007-2010: Senior postdoctoral fellow. Research team led by Dr Dino A. Giussani. Department of Physiology, Development & Neuroscience, University of Cambridge, UK.

    Interés Científico (resumen)

    Our ongoing investigation associates a group of Chilean, German, Scottish and English senior and young researchers with a common interest in developmental aspects of chronobiology as well as fetal programming of adult disease and their probable underlying mechanisms: chromatin remodeling, inflammation and oxidative stress. As for the latter prenatal insult, in recent reports we have demonstrated that the long term cardiovascular adverse effects of fetal hypoxia and undernutrition are programmed by oxidative stress and may be ameliorated by treatment of the pregnant dams with vitamin C or melatonin. However, the core long term goal of our research network, which is coordinated from our Laboratory of Developmental Chronobiology  (Valdivia, Chile), is establishing the risks of shift work, and how this system enforced by modern 24/7 society does impact our health at different levels. In this context, we are mainly interested in modeling the adverse pregnancy outcomes imposed by shift worker women on their offspring, particularly those which carry on into adulthood (i.e., developmental programming of adult chronic disease by gestational chronodisruption). Previously, epidemiological studies on the effects of chronodisruption on gestational outcomes had reported increased preterm delivery and low birth weight at term; both being strong predictors of late onset chronic disease. These findings prompted us to address the impact of chronodisruption during pregnancy on fetal global gene expression in different tissues. Using an integrative approach applied to longitudinal cohorts, at the behavioral, pathophysiological, systems, isolated organ, cellular and molecular levels, we are now determining whether and how metabolism, inflammatory response, transcriptional regulation, epigenetics, neuroendocrinology, circadian rhythms, cognitive behavior and cardiovascular physiology are individually or collectively affected in the adult offspring gestated under chronodisruption conditions. Our functional genomics analyses of genome-wide fetal gene expression have uncovered a number of pathophysiological deregulations inside different gene networks, which strongly correlate with our findings in the adult offspring which had been gestated under altered photoperiod, including: hypertrophic cardiomyopathy, significant differences in spatial cognitive skills and fasting glucose level, a prolonged response to intraperitoneal glucose, as well as decreased plasma levels of melatonin, corticosterone and C3/C4 complement factors. Notably, several of these fetal and adult pathophysiological alterations were reversed in the fetal and adult offspring of mothers receiving melatonin every day during gestation.

    Líneas de Investigación

    • Cronobiología del desarrollo y programación fetal de enfermedades del adulto.

    Proyectos Vigentes

    II Versión Congreso del Futuro Región de Los Ríos: difusión de la ciencia, la tecnología y la innovaciónPrograma de Apoyo al Emprendimiento e Innovación CORFO 16PAEI-68007. Años 2016-2017. Director.

    High-throughput and top-down systems biology analysis of multi-tissue molecular changes in response to developmental chronodisruption. Proyecto Regular FONDECYT 1150069. Años 2015-2019. Investigador Responsable.

  • Publicaciones Relevantes de los últimos 10 años

    1. Torres-Farfan C, Valenzuela FJ, Ebensperger R, Méndez N, Campino C, Richter HG, Valenzuela GJ, Serón-Ferré M. Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus apella). American Journal of Primatology, 2008; 70(1): 93-100
    2. Richter HG, Torres-Farfan C, Garcia-Sesnich J, Abarzua-Catalan L, Henriquez MG, Alvarez-Felmer M, Gaete F, Rehren GE, Seron-Ferre M. Rhythmic expression of functional MT1 melatonin receptors in the rat adrenal gland. Endocrinology, 2008; 149(3): 995-1003
    3. Valenzuela FJ, Torres-Farfan C, Richter HG, Mendez N, Campino C, Valenzuela GJ, Torrealba F, Seron-Ferre M. Clock gene expression in adult primate suprachiasmatic nuclei and adrenal gland: is the adrenal a peripheral clock responsive to melatonin? Endocrinology, 2008; 149(4): 1454-1461
    4. Richter HG, Hansell JA, Raut S, Giussani DA. Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy. Journal of Pineal Research, 2009; 46(4):357-364. doi: 10.1111/j.1600-079X.2009.00671.x.
    5. Torres-Farfan C, Abarzua-Catalan L, Valenzuela FJ, Mendez N, Richter HG, Valenzuela GJ, Seron-Ferre M. Cryptochrome 2 (CRY2) expression level is critical for ACTH-stimulation of cortisol production in the capuchin monkey adrenal. Endocrinology, 2009; 150(6): 2717-2722. doi: 10.1210/en.2008-1683.
    6. Adler A, Camm EJ, Hansell JA, Richter HG, Giussani DA. Investigation of the use of antioxidants to diminish the adverse effects of postnatal glucocorticoid treatment on mortality and cardiac development. Neonatology, 201098(1): 73-83. doi: 10.1159/000275561.
    7. Thakor AS, Richter HG, Kane AD, Dunster C, Kelly FJ, Poston L, Giussani DA. Redox modulation of the fetal cardiovascular defence to hypoxaemia. Journal of Physiology, 2010588(21): 4235-4247. doi: 10.1113/jphysiol.2010.196402.
    8. Camm EJ, Tijsseling D, Richter HG, Adler A, Hansell JA, Derks JB, Cross CM, Giussani DA. Oxidative stress in the developing brain: Effects of postnatal glucocorticoid therapy and antioxidants. PLoS ONE, 2011; 6(6): e21142. doi:10.1371/journal.pone.0021142
    9. Giussani DA, Camm EJ, Niu Y, Richter HG, Blanco CE, Gottschalk R, Mullender JL, Blake EZ, Horder KA, Thakor AS, Hansell JA, Kane AD, Wooding P, Cross CM, Herrera EA. Developmental programming of cardiovascular dysfunction by prenatal hypoxia and oxidative stress. PLoS ONE, 2012; 7(2): e31017. doi:10.1371/journal.pone.0031017
    10. Richter HG, Camm EJ, Modi BN, Naeem F, Cross CM, Cindrova-Davies T, Spasic-Boskovic O, Dunster C, Mudway IS, Kelly FJ, Burton GJ, Poston L, Giussani DA. Ascorbate prevents placental oxidative stress and enhances birth weight in hypoxic pregnancy in rats. Journal of Physiology, 2012; 590(6): 1377-1387. doi: 10.1113/jphysiol.2011.226340.
    11. Mendez N, Abarzua-Catalan L, Vilches N, Galdames HA, Spichiger CE, Richter HG, Valenzuela GJ, Seron-Ferre M, Torres-Farfan C. Timed Maternal Melatonin Treatment Reverses Circadian Disruption of the Fetal Adrenal Clock Imposed by Exposure to Constant Light. PLoS ONE, 2012; 7(8): e42713. doi:10.1371/journal.pone.0042713
    12. Tijsseling D, Camm EJ, Richter HG, Herrera EA, Kane AD, Niu Y, Cross CM, de Vries WB, Derks JB, Giussani DA. Statins prevent adverse effects of postnatal glucocorticoid therapy on the developing brain in rats. Pediatric Research, 2013; 74(6):639-645. doi: 10.1038/pr.2013.152.
    13. Kane A, Camm EJ, Richter HG, Lusby C, Tijsseling D, Kaandorp J, Derks J, Ozanne S, Giussani DA. Maternal to fetal allopurinol transfer and xanthine oxidase suppression in the late gestation pregnant rat., 2013; 1(6):  e00156. doi:10.1002/phy2.156
    14. Galdames HA, Torres-Farfan C, Spichiger C, Mendez N, Abarzua-Catalan L, Alonso-Vazquez P, Richter HG. Impact of gestational chronodisruption on fetal cardiac genomics. Journal of Molecular and Cellular Cardiology, 2014; 66C:1-11. doi: 10.1016/j.yjmcc.2013.10.020.
    15. Vilches N, Spichiger CE, Mendez N, Abarzua-Catalan L, Galdames HA, Hazlerigg DG, Richter HG, Torres-Farfan C. Gestational chronodisruption impairs hippocampal expression of NMDA receptor subunits Grin1b/Grin3a and spatial memory in the adult offspring. PloS One, 2014; 9(3): e91313. doi:10.1371/journal.pone.0091313
    16. Amaral F, Castrucci AM, Cipolla-Neto J, Poletini MO, Mendez N, Richter HG, Sellix MT. Environmental Control of Biological Rhythms: Effects on Development, Fertility and Metabolism. Journal of Neuroendocrinology, 2014; 26(9):603-612. doi: 10.1111/jne.12144
    17. Giussani DA, Niu Y, Herrera EA, Richter HG, Camm EJ, Thakor AS, Kane AD, Hansell JA, Brain KL, Skeffington KL, Itani N, Wooding FB, Cross CM, Allison BJ. Heart disease link to fetal hypoxia and oxidative stress. Advances in Experimental Medicine and Biology, 2014; 814:77-87. doi: 10.1007/978-1-4939-1031-1_7.
    18. Spichiger C, Torres-Farfan C, Galdames HA, Mendez N, Alonso-Vazquez P, Richter HG. Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver. Physiological Genomics, 2015; 47(12):621-633. DOI: 10.1152/physiolgenomics.00023.2015.
    19. Serón-Ferré M, Richter HG, Valenzuela GJ, Torres-Farfan C. Circadian rhythms in the fetus and newborn: significance of interactions with maternal physiology and the environment. In: David Walker (Ed.), Prenatal and Postnatal Determinants of Development (Neuromethods), Springer New York, USA, 2016, pp. 147-165
    20. Mendez N, Halabi D, Spichiger C, Salazar E, Vergara K, Alonso-Vasquez P, Carmona P, Sarmiento JM, Richter HG, Seron-Ferre M, Torres-Farfan C. Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease. Endocrinology, 2016; 157(12):4654-4668.

  • Asistentes de Investigación

    Asistentes de Investigación de planta UACh/personal apoyo:

    • María Clara Jara, Bioquímico (Escalafón Profesional UACh).

    Asistentes de Investigación pagados por proyectos:

    • Dr. Carlos Spichiger, Postdoctorante
    • Karina Vergara, Ingeniero
    • Miguel Villanueva, Técnico

    Alumnos de postgrado vigentes:

    • Natalia Méndez (Doctorado en Ciencias Médicas, UACh)
    • Pamela Alonso (Magister en Neurociencias, UACh)

    Principales Colaboradores

    Principales Co-investigadores UACh:

    • Dra. Claudia Torres-Farfan
    • Dr. José Sarmiento

    Principales Colaboradores Nacionales e Internacionales:

    Nacionales

    • Dra. María Serón-Ferré: Departamento de Fisiopatología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.
    • Dra. Soraya Gutierrez: Laboratorio de regulación transcripcional, Departamento de Bioquímica y Biología Molecular, Universidad de Concepción, Concepción, Chile.
    • Dr. Emilio Herrera: Departamento de Fisiopatología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile.

    Internacionales

    • Dr. Dino Giussani: Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, United Kingdom.
    • Dr. Horst-Werner Korf: Dr. Senckenbergische Anatomie, Institute of Anatomy III, Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
    • Dr. David Hazlerigg: School of Biological Sciences, 309 Zoology Building, Tillydrone Avenue, Aberdeen, Scotland.
    • Dr. José Cipolla-Neto: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

  • Contacto