Research SummaryGeneral interest is in mammalian reproduction and environmental epigenetics on a systems biology level. The laboratory has had a long standing research program to study gonadal development and function on a molecular, cellular and physiological level (systems biology). More recently, the ability of environmental factors to act on gonadal development has been shown to cause the epigenetic transgenerational inheritance of disease and phenotypic variation which impacts areas of biology such as medicine or evolution. This has now become a predominant research program in the lab.
Basic research projects involve the investigation of how different cell types in a tissue interact and communicate to regulate cellular growth and differentiation, with emphasis in the area of reproductive biology. The cells of interest and specific interactions investigated have an integral role in controlling the development of the spermatozoa and oocyte. Our observations indicate that the mesenchymal cells of both the testis and ovary produce inducer substances that alter the differentiation and function of adjacent epithelial cells. The role that reproductive hormones (e.g. steroids) and growth factors (e.g. transforming growth factors, neurotropins) have in regulating these mesenchymal-epithelial cell interactions is under investigation. How these factors promote the transcriptional regulation of cellular differentiation is being investigated through an analysis of the role of a unique class of transcription factors, basic-helix-loop-helix (bHLH) factors. Information obtained from these studies is necessary before novel therapeutic agents can be designed and targeted at reproductive cells for the prevention of infertility or to act as contraceptives. The research is designed to understand testis and ovary development and function on a systems biology level.
Previously we have found that environmental toxicants (e.g. endocrine disruptors) have the ability to modify local cell-cell interactions in the testis and ovary during fetal development that influences epigenetic programming of the germline. If gestating females are exposed to environmental toxicants (e.g. endocrine disruptors) at the time of fetal gonadal sex determination, a number of adult onset diseases develop. Interestingly this phenotype is transgenerational, such that what your pregnant great grandmother was exposed to may cause disease in you with no subsequent exposure. This has been termed epigenetic transgenerational inheritance. An epigenetic effect on the programming of the germ-line was observed and is the causal factor in this epigenetic transgenerational effect of environmental toxicants. In addition to effects on reproduction, numerous other adult onset disease sates are observed including cancer, prostate disease, kidney disease, obesity, immune abnormalities and behavior effects. Further characterization of this phenomena and its impact on disease etiology and evolutionary biology is in progress. Further information is available at www.skinner.wsu.edu.
Research PublicationsShnorhavorian M, Schwartz S, Sadler-Riggleman I, Beck D, Skinner MK (2017) Differential DNA Methylation Regions in Adult Human Sperm Following Adolescent Chemotherapy: Potential Epigenetic Inheritance from Chemotherapy. Plos One 12(2): e0170085.
Carvan MJ, Kalluvila TA, Klingler RH, Larson JK, Pickens M, Mora-Zamorano FX, Connaughton VP, Sadler-Riggleman I, Beck D, Skinner MK (2017) Mercury Induced Epigenetic Transgenerational Inheritance of Abnormal Phenotypes and Sperm Epimutations in Zebra Fish. Plos One 12(5): e0176155.
McNew S, Beck D, Sadler-Riggleman I, Knutie SA, Koop JAH, Clayton DH, Skinner MK (2017) Epigenetic variation between urban and rural populations of Darwin’s finches. BMC Evolutionary Biology 17:183.
Thorson JLM, Smithson M, Beck D, Sadler-Riggleman I, Nilsson E, Dybdahl M, Skinner MK (2017) Epigenetics and adaptive phenotypic variation between habitats in an asexual snail. Scientific Reports. 7(1):14139.
Holder LB, Haque MM, Skinner MK (2017) Machine Learning for Epigenetics and Future Medical Applications. Epigenetics 19:1-10
Gartstein MA, Skinner MK (2017) Prenatal Influences on Temperament Development: The Role of Environmental Epigenetics. Development & Psychopathology. Dec 12:1-35. (ePub ahead of print).
Beck D, Sadler-Riggleman I, Skinner MK (2017) Generational Comparisons (F1 versus F3) of Vinclozolin Induced Epigenetic Transgenerational Inheritance of Sperm Differential DNA Methylation Regions (Epimutations) Using MeDIP-Seq. Environmental Epigenetics 3(3): dvx016.
Skinner MK (2017) Research Highlight: Environment. Epigenetics and Reproduction. Environmental Epigenetics 3(3)1-2. Dvx018.
McBirney M, King SE, Pappalardo M, Houser E, Unkefer M, Nilsson E, Sadler-Riggleman I, Beck D, Winchester P, Skinner MK (2017) Atrazine Induced Epigenetic Transgenerational Inheritance of Disease, Lean Phenotype and Sperm Epimutation Pathology Biomarkers. Plos One 12(9):e0184306.
Skinner MK (2016) Endocrine disruptors in 2015: Epigenetic transgenerational inheritance. Nature Review Endocrinology 12(2):68-70.
Haque MM, Nilsson EE, Holder LB, Skinner MK (2016) Genomic Clustering of differential DNA methylated regions (epimutations) associated with the epigenetic transgenerational inheritance of disease and phenotypic variation. BMC Genomics 17:418.
Hanson MA, Skinner MK (2016) Developmental Origins of Epigenetic Transgenerational Inheritance. Environmental Epigenetics 2(1):1-9.
Schuster A, Skinner MK, Yan W (2016) Ancestral vinclozolin exposure alters the epigenetic transgenerational inheritance of sperm small noncoding RNA. Environmental Epigenetics 2(1):1-10.
Guillette L, Parrott B Nilsson EE, Haque MM, Skinner MK (2016) Epigenetic Programming Alterations in Alligators from Environmentally Contaminated Lakes. General and Comparative Endocrinology. 1;238:4-12.
Skinner MK (2016) Differential DNA Methylation Analysis Optimally Requires Purified Cell Populations. Fertility and Sterility 1;106(3):551.
McCarrey JR, Lehle JD, Raju SS, Wang Y, Nilsson EE, Skinner MK (2016) Tertiary Epimutations - A Novel Aspect of Epigenetic Transgenerational Inheritance Promoting Genome Instability. PLoS One. 19;11(12):e0168038.
Skinner MK (2016) Unified theory of evolution: Environmental Epigenetics Allows a Lamarckian Concept to Facilitate Darwinian Evolution. Aeon, Online Magazine, November 9