Participating Faculty
Michael Skinner

Michael Skinner

Department:School of Biological Sciences, WSU
Credentials:1982~Ph.D., Washington State University
Office:Abelson Hall 507
Phone:509-335-1524
Fax:509-335-2176
Mailing Address:School of Biological Sciences
PO Box 644236
Pullman, WA 99164-4236
E-mail:skinner@wsu.edu
Web Site:Click here


Research Interests

Molecular And Cellular Control Of Testis And Ovary Biology And Development, As Well As Epigenetic Transgenerational Actions Of Environmental Compounds On Reproduction And Disease

Research Summary

General 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 Publications

Selected 2009-2012

Mohan Manikkam, Rebecca Tracey, Carlos Guerrero-Bosagna & Michael K. Skinner (2013) "Plastics Derived Endocrine Disruptors (BPA, DEHP and DBP) Induce Epigenetic Transgenerational Inheritance of Adult-Onset Disease and Sperm Epimutations." PLoS ONE 8(1):e55387.

Rebecca Tracey, Mohan Manikkam, Carlos Guerrero-Bosagna, & Michael K. Skinner (2013) "Hydrocarbon (Jet Fuel JP-8) Induces Epigenetic Transgenerational Inheritance of Adult-Onset Disease and Sperm Epimutations." Reproductive Toxicology (epub ahead of print).

Carlos Guerrero-Bosagna, and Michael K. Skinner (2012) "Environmental Epigenetics and Phytoestrogen/Phytochemical Exposures." JSBMB (epub ahead of print). doi:pii: S0960-0760(12)00271-3.

Guerrero-Bosagna C and Skinner MK (2012) "Environmentally Induced Epigenetic Transgenerational Inheritance of Phenotype and Disease." Molecular and Cellular Endocrinology 6;354(1-2):3-8.

Crews D, Gillette R, Manikkam M, Savenkova M and Skinner MK (2012) "Epigenetic transgenerational inheritance of altered stress responses." PNAS 5;109(23):9143-8.

Carlos Guerrero-Bosagna, Trevor R. Covert, Matthew Settles, Matthew D. Anway, and Michael K. Skinner. (2012) "Epigenetic Transgenerational Inheritance of Vinclozolin Induced Mouse Adult Onset Disease and Associated Sperm Epigenome Biomarkers." Reproductive Toxicology 34(4):694-707.

Eric Nilsson, Ginger Larsen, Mohan Manikkam, Carlos Guerrero-Bosagna, Marina Savenkova and Michael K. Skinner (2012) "Environmentally induced epigenetic transgenerational inheritance of ovarian disease." PLoS One. 7(5):e36129.

Mohan Manikkam, Carlos Guerrero-Bosagna, Rebecca Tracey, Md. M. Haque and Michael K. Skinner (2012) "Transgenerational Actions of Environmental Compounds on Reproductive Disease and Identification of Epigenetic Biomarkers of Ancestral Exposures." PLoS ONE 7(2):e31901.

Bhandari R, Haque Md, Skinner MK (2012) "Global Genome Analysis of the Downstream Binding Targets of Testis Determining Factor SRY AND SOX9." PLoS ONE 7(9):e43380.

Bhandari R, Schinke E, Haque Md, Skinner MK (2012) "SRY Induced TCF21 Genome-wide Targets and Cascade of bHLH Factors During Sertoli Cell Differentiation and Male Sex Determination." Biology of Reproduction 6;87(6):131.

Skinner MK, Manikkam M, Haque Md., Zhang B, Savenkova M (2012) "Epigenetic Transgenerational Inheritance of Somatic Transcriptomes and Epigenetic Control Region." Genome Biology 3;13(10):R91.

Mohan Manikkam, Rebecca Tracey, Carlos Guerrero-Bosagna, and Michael K. Skinner (2012) "Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations." PLoS ONE 7(9): e46249.

Mohan Manikkam, Rebecca Tracey, Carlos Guerrero-Bosagna, Michael K. Skinner (2012) "Pesticide and Insect Repellent Mixture (Permethrin and DEET) Induces Epigenetic Transgenerational Inheritance of Disease and Sperm Epimutations." Reproductive Toxicology 34(4):708-19.

Clement, T. M., R. K. Bhandari, et al. (2011). "SRY Directly Regulates the Neurotrophin 3 Promoter During Male Sex Determination and Testis Development in Rats." Biology of Reproduction.

Skinner, M. K., M. Manikkam, et al. (2011). "Epigenetic transgenerational actions of endocrine disruptors." Reproductive Toxicology 31(3): 337-343.

Clement, T. M., M. I. Savenkova, et al. (2010). "Alterations in the developing testis transcriptome following embryonic vinclozolin exposure." Reproductive Toxicology 30(3): 353-364.

Guerrero-Bosagna, C., M. Settles, et al. (2010). "Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome." PloS One 5(9).

Nilsson, E. E., M. I. Savenkova, et al. (2010). "Gene bionetwork analysis of ovarian primordial follicle development." PloS One 5(7): e11637.

Schindler, R., E. Nilsson, et al. (2010). "Induction of ovarian primordial follicle assembly by connective tissue growth factor CTGF." PloS One 5(9): e12979.

Skinner, M. K. (2010). "Metabolic disorders: Fathers' nutritional legacy." Nature 467(7318): 922-923.

Skinner, M. K., M. Manikkam, et al. (2011). "Epigenetic transgenerational actions of endocrine disruptors." Reproductive Toxicology 31(3): 337-343.

Skinner, M. K., M. Manikkam, et al. (2010). "Epigenetic transgenerational actions of environmental factors in disease etiology." Trends in Endocrinology and Metabolism: TEM 21(4): 214-222.

Skinner, M. K., A. Rawls, et al. (2010). "Basic helix-loop-helix transcription factor gene family phylogenetics and nomenclature." Differentiation; research in biological diversity 80(1): 1-8.

Nilsson, E., G. Dole, et al. (2009). "Neurotrophin NT3 promotes ovarian primordial to primary follicle transition." Reproduction 138(4): 697-707.

Washington State University