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DVM
Mirella Meyer-Ficca

Mirella Meyer-Ficca

Research Assistant Professor
Animal, Dairy and Veterinary Sciences: DVM, Faculty , Research Faculty
Location:  CIB 311
Office Phone:  435-797-1685
Fax:  435-797-2766
UMC 4700

Position Available

Specialties: germline epigenetics, environmental reproductive toxicology

About Me

My main research interest is to understand how environmental factors (e.g. exposure to toxicants, dietary conditions, oxidative stressors, etc.) can change the germ-line epigenome, and thus indirectly gene regulation in offspring, and influence their health and disease.

The epigenome comprises additional levels of structural and biochemical information superimposed to the primary DNA sequence information, such as nuclear architecture and genome organization, DNA methylation, posttranslational modification the chromatin associated proteins, e.g. histones, and small RNAs. Epigenetic control appears to be for the development of complex and often late-onset diseases, such as cancer, diabetes and autism.

My lab is particularly interested in exposures that occur during the prenatal phase of germ cell development. In other words, we focus on this central question: How does exposure of a pregnant mother to adverse environmental factors influence the germ-line epigenome of the developing offspring?

A thorough understanding of the relevant mechanisms will help us to develop adequate lifestyle choices and pharmacological interventions that can improve human and animal health, which is our long-term goal.

Undergraduate and graduate student opportunities in the lab are currently available – please contact me by email: Mirella.Meyer@usu.edu. Take a look at the opening here.

Research projects in my lab address individual facets of this central question:

  1. Which epigenetic alterations of the germ line occur as a consequence of adverse prenatal conditions?
  2. What are the molecular mechanisms that translate environmental conditions into epigenetic information and control imprint establishment in germ line cells?
  3. What are consequences of an altered germ-line epigenome for fertility of the individual and health of his offspring?

One of the potential candidate mechanisms my lab currentlyfocuses on is poly(ADP-ribosyl)ation (PARsylation). PARsylation is a biochemical pathway that is central to DNA repair and chromatin remodeling processes in all mammalian cells. It can change DNA integrity and the epigenetic make up of DNA, e.g. nuclear architecture, chromatin composition and DNA methylation patterns. Its level of activity largely depends on exogenous factors, such as the availability of certain nutrients (niacin), and cellular exposure to oxidative stressors or other environmental toxicants.

My prior research focused on the role of PARsylation during the continually ongoing germ cell differentiation (spermatogenesis) that occurs in adult males. Those studies demonstrated in genetic and pharmacological rodent models that proper PARsylation is required for normal sperm chromatin composition and nuclear organization, two important layes of the epigenetic information contained within each sperm.

My research has been supported by funds from The Found Animals Foundation, start-up funding from the Utah State University and by a Research Catalyst grant from the Utah State University’s Office of Research and Graduate Studies.

Between 1992 and 1997, I studied Biology and Chemistry at the University of Kaiserslautern (TU Kaiserslautern), Germany, and 1997 received the German Diploma in Biology (equivalent to M.S., with major focus on Genetics, Human Genetics and Organic Chemistry). For graduate training and doctoral research I moved to the Eberhard-Karls-University of Tübingen and the University Hospital of Tübingen, Germany, where I focused on Virology and Human Genetics, and received my Ph.D. degree (Dr.rer.nat., Doctorate in Natural Sciences) in 2002.

In 2002, I joined the University of Arizona (Arizona Cancer Center and College of Pharmacy, Department of Pharmacology and Toxicology) as post-doctoral research associate and received further training in Cancer Biology and Toxicology. Between 2005 and 2013, I worked as a Senior Research Investigator at the University of Pennsylvania, conducting research in the fields of Male Reproductive Biology and Toxicology. In 2013, I joined Utah State University as Research Assistant Professor in the Department of Animal, Dairy and Veterinary Sciences and the School of Veterinary Medicine, where I teach Veterinary Toxicology.

 


For Students

  • Classes I Teach
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    Course name:  Veterinary Toxicology 
    Course number:  VM7523, Course Director
    Description: Students will learn about pharmacology and toxicology of the systems of domestic animals.
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Education

  • Education & Training
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    M.S., Biology (German Diplom-Biologin)
    1997, University of Kaiserslautern, Germany
    Thesis: Molecular Cytogenetic Analysis of Spermiogenesis in the Rat
     
    Ph.D. (Dr.rer.nat.)
    2002, Eberhard-Karls-Universität Tübingen, Germany
    Dissertation: Analyses of Cytotoxicity of the Cardiotropic Coxsackievirus B3 and Development of Strategies for Immortalization of human Cardiomyocytes
     
    Postdoc in Pharmacology and Toxicology
    2002-2005, University of Arizona
    Research Focus: Role of Poly(ADP-ribosyl) ation for Genomic Integrity
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  • Peer Reviewed Research Articles
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    For a complete list of publications click here.
     
    The 10 most recent publications:
     
    1. Gao H., Coyle D.L., Meyer-Ficca M.L., Meyer R.G., Jacobson E.L., Wang Z.Q., Jacobson M.K. (2007) Altered poly(ADP-ribose) metabolism impairs cellular responses to genotoxic stress in a hypomorphic mutant of poly(ADP-ribose) glycohydrolase. Exp Cell Res 313(5):984-96.
    2. Meyer R.G., Meyer-Ficca M.L., Whatcott C.J., Wang Z.Q., Jacobson M.K. (2007) Two small enzyme isoforms mediate mammalian mitochondrial poly(ADP-ribose) glycohydrolase (PARG) activity. Exp Cell Res 313(13):2920-36.
    3. Meyer-Ficca M.L., Lonchar J.D., Credidio C., Ihara M., Li Y., Wang Z.Q., Meyer R.G. (2009) Disruption of Poly(ADP-Ribose) Homeostasis Affects Spermiogenesis and Sperm Chromatin Integrity in Mice. Biol Reprod 81(1):46-55. Epub Mar 4, 2009
    4. Whatcott C.J., Meyer-Ficca M.L., Meyer R.G., Jacobson M.K. (2009) A specific isoform of poly(ADP-ribose) glycohydrolase is targeted to the mitochondrial matrix by a N-terminal mitochondrial targeting sequence.
    Exp Cell Res 315(20):3477-85. Epub Apr 21, 2009.
    5. Meyer-Ficca M.L., Lonchar J.D., Ihara M., Meistrich M.L., Austin C.A., Min W., Wang Z.Q., Meyer R.G. (2011) Poly(ADP-ribose) metabolism is essential for proper nucleoprotein exchange during mouse spermiogenesis. Biol Reprod 84(2):218-28, 2011.
    6. Meyer-Ficca M.L., Ihara M., Lonchar J.D., Meistrich M.L., Austin C.A., Meyer R.G. (2011) Poly(ADP-ribose) polymerases PARP1 and PARP2 modulate topoisomerase II beta (TOP2B) function during chromatin condensation in murine spermiogenesis. Biol Reprod 84(5):900-9, 2011.
    Highlighted in Editorial: Ward W.S. Regulating DNA Supercoiling: Sperm Points the Way. Biol Reprod 84(5):841-3, 2011.
    7. Meyer-Ficca M.L., Meyer, R.G. (2011) Genetic approaches to targeting multiple PARP genes in a mammalian genome. Methods in Molecular Biology, Methods Mol Biol. 2011;780:349-76.
    8. Bryant, J. M., Meyer-Ficca M. L., Dang V. M., Berger S. L., Meyer R. G. (2013) Separation of Spermatogenic Cell Types using STA-PUT Velocity Sedimentation. Journal of Visual Experiments, J Vis Exp. 2013 Oct 9;(80).
    9. Meyer-Ficca M. L., Lonchar J. D., Ihara M., Bader J. J., Meyer R. G. (2013) Alteration of poly(ADP-ribose) metabolism affects murine sperm nuclear architecture by impairing pericentric heterochromatin condensation. Chromosoma. 2013 Aug;122(4):319-35.
    10. Ihara M, Meyer-Ficca ML, Leu NA, Rao S, Li F, Gregory BD, Zalenskaya IA, Schultz RM, Meyer RG. (2014) Paternal poly (adp-ribose) metabolism modulates retention of inheritable sperm histones and early embryonic gene expression. PLoS Genet. 2014 May 8;10(5):e1004317. doi: 10.1371/journal.pgen.1004317. eCollection 2014
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  • Patents
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    1. Küpper J-H, Meyer R, Meyer-Ficca M, Kandolf R. Coxsackievirus B3 Vectorsystems for Gene Terapy. German patent application DE 199 39 095.9, priority August 18, 1999; International patent application PCT/EP00/07768.
    2. Küpper J-H, Meyer R, Meyer-Ficca M, Kandolf R. Tumor-specific vector for Gene Terapy. German patent application DE 199 47 668.3, priority October 4, 1999; International patent application PCT/EP00/08921. 
    3. Küpper J-H, Meyer R, Meyer-Ficca M, Kuhn A. Transient Immortalization. German patent application DE 101 52 972.4, priority October 18, 2001. International patent application PCT/EP02/11200.(Patent assignees: 1: University Hospital of Tuebingen, Germany, 2-3: Heart BioSystems GmbH, Tuebingen, Germany)
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  • Financial Support
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    My research has been supported by funds from The Found Animals Foundation, start-up funding from the Utah State University and by a Research Catalyst grant from the Utah State University’s Office of Research and Graduate Studies.
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  • Book Chapters
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    Meyer R.G., Meyer-Ficca M.L., Jacobson E.L., Jacobson M.K. (2004) Enzymes in poly(ADP-ribose) metabolism; bookchapter in: Burkle, A (ed): Poly(ADP-ribosyl)ation, Landes Bioscience, ISBN 1-58706-292-5
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Honors and Activities

  • Honors & Awards
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    2004
    Special Recognition Award in Basic Science, American Association for Cancer Research,
    AACR Pathobiology of Cancer: The Edward A. Smuckler Memorial Workshop, Snowmass Village, Colorado

    2004
    Travel Award, The 53rd Fujihara International Seminar,
    Tomakomai, Hokkaido, Japan, The Fujihara Foundation of Science

    2011
    Travel Award, XXIst North American Testis Workshop, Montreal, Quebec, Canada

    2011
    Susan Heyner Award for Excellence in Research, Center for Research on Reproduction and Women’s Health, University of Pennsylvania, Philadelphia, Pennsylvania

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  • Professional Membership
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    2001-2002
    European Society for Gene Therapy

    2003-2008
    Associate Member, American Association for Cancer Research, AACR

    2008
    Member, American Association for Cancer Research, AACR

    2005
    Member, German Society for DNA Repair Research, DGDR

    2009
    Member, American Society for Andrology

    2011
    Member, Society for the Study of Reproduction

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  • Peer Review
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    Analytical Biochemistry
    Experimental Cell Research
    Int J Biochem Cell Biol
    Cell & Tissue Research
    Molecular Aspects of Medicine
    Fertility and Sterility
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