Kathrin Muegge, M.D.
Kathrin  Muegge, M.D.
Senior Investigator (Contr)
Head, Epigenetics Section

Dr Muegge studies molecular mechanisms that alter chromatin structure and function during murine development. She discovered several links between chromatin modifiers, including nucleosomal remodeling and DNA methylation.

The work focuses on chromatin changes during normal cellular differentiation and during the reverse process of nuclear reprogramming. Her studies provide insights how stable gene expression is achieved, how cells maintain a proper phenotype, and how this process may be disturbed in pathologic conditions including cancer.

Areas of Expertise
1) nucleosomal remodeling, 2) DNA methylation, 3) histone modification, 4) embryonal stem cell differentiation, 5) reprogramming, 6) murine development

Contact Info

Kathrin Muegge, M.D.
Center for Cancer Research
National Cancer Institute
Building 469, Room 243
Frederick, MD 21702-1201
301-846-1386
Kathrin.Muegge@nih.gov

Lsh, a Guardian of Heterochromatin

Epigenetic modifications comprising DNA methylation and histone modifications are crucial for organization of the genome into active chromatin (euchromatin) and repressed chromatin (heterochromatin). The functional organization of chromatin is important for regulation of transcription, cellular differentiation, imprinting and normal mitosis. Our group studies the role of epigenetic modifications that control chromatin structure, in particular DNA methylation during normal embryonic development and during cancer development. The current focus of our studies is to understand the molecular mechanisms and biological role of lymphoid-specific helicase (Lsh).

Lsh is a chromatin remodeling protein that we previously identified, cloned and characterized. Lsh is predominantly found in lymphoid tissues in the adult animal, but it is ubiquitously expressed during embryogenesis. Lsh is a crucial factor for normal embryonic development since targeted deletion of Lsh leads to death of the newborn animal. Lsh is a component of pericentromeric heterochromatin and Lsh deficiency results in a greatly perturbed heterochromatin organization with loss of DNA methylation and altered histone tail acetylation and methylation. As a functional consequence of perturbed pericentromeric heterochromatin we observe aberrant reactivation of "parasitic" elements (such as endogenous retroviral elements) and abnormal mitosis with amplified centrosomes and genomic instability. Thus Lsh is a major epigenetic regulator that controls DNA methylation patterns and is crucial for normal heterochromatin structure and function. We are currently testing the role of Lsh and genomic demethylation in tumor progression. These studies should provide insights into a number of basic biologic processes that involve epigenetic modifications such as transcription, imprinting, mitosis and cellular transformation.

Scientific Focus Areas:
Cancer Biology, Chromosome Biology, Developmental Biology, Stem Cell Biology

View Dr. Muegge's PubMed Summary.

Selected Key Publications
  1. Tao Y, Xi S, Shan J, Maunakea A, Che A, Briones V, Lee EY, Geiman T, Huang J, Stephens R, Leighty RM, Zhao K, Muegge K.
    Proc Natl Acad Sci U S A. 108: 5626-31, 2011. [ Journal Article ]
  2. Tao Y, Liu S, Briones V, Geiman TM, Muegge K
    Nucleic Acids Res. 39: 9508-20, 2011. [ Journal Article ]
  3. von Eyss B, Maaskola J, Memczak S, Möllmann K, Schuetz A, Loddenkemper C, Tanh MD, Otto A, Muegge K, Heinemann U, Rajewsky N, Ziebold U.
    EMBO J. 31: 972-85, 2012. [ Journal Article ]
  4. Yu W, Briones V, Lister R, McIntosh C, Han Y, Lee EY, Ren J, Terashima M, Leighty RM, Ecker JR, Muegge K.
    Proc Natl Acad Sci U S A. 111: 5890-5, 2014. [ Journal Article ]
  5. Yu W, McIntosh C, Lister R, Zhu I, Han Y, Ren J , Landsman D, Lee E, Briones V, Terashima M, Leighty R, Ecker JR, Muegge K
    Genome Res. 24: 1613-23, 2014. [ Journal Article ]

Dr. Muegge obtained her M.D. degree at the Medical School Hannover, Germany. During her postdoctoral period she worked on cytokines and T cell development in the Laboratory of Molecular Immunoregulation of Dr. Joost Oppenheim and Dr. Scott Durum. As a Principal Investigator at the National Cancer Institute in Frederick, she now investigates in the Laboratory of Cancer Prevention chromatin organization during embryonic development and in tumor progression.

Name Position
Samantha Barbour Postbaccalaureate Fellow
Yixing Han Postdoctoral Fellow (Visiting)
Jianke Ren Postdoctoral Fellow (Visiting)
Weishi Yu Ph.D. Postdoctoral Fellow (Visiting)

Research

Lsh, a Guardian of Heterochromatin

Epigenetic modifications comprising DNA methylation and histone modifications are crucial for organization of the genome into active chromatin (euchromatin) and repressed chromatin (heterochromatin). The functional organization of chromatin is important for regulation of transcription, cellular differentiation, imprinting and normal mitosis. Our group studies the role of epigenetic modifications that control chromatin structure, in particular DNA methylation during normal embryonic development and during cancer development. The current focus of our studies is to understand the molecular mechanisms and biological role of lymphoid-specific helicase (Lsh).

Lsh is a chromatin remodeling protein that we previously identified, cloned and characterized. Lsh is predominantly found in lymphoid tissues in the adult animal, but it is ubiquitously expressed during embryogenesis. Lsh is a crucial factor for normal embryonic development since targeted deletion of Lsh leads to death of the newborn animal. Lsh is a component of pericentromeric heterochromatin and Lsh deficiency results in a greatly perturbed heterochromatin organization with loss of DNA methylation and altered histone tail acetylation and methylation. As a functional consequence of perturbed pericentromeric heterochromatin we observe aberrant reactivation of "parasitic" elements (such as endogenous retroviral elements) and abnormal mitosis with amplified centrosomes and genomic instability. Thus Lsh is a major epigenetic regulator that controls DNA methylation patterns and is crucial for normal heterochromatin structure and function. We are currently testing the role of Lsh and genomic demethylation in tumor progression. These studies should provide insights into a number of basic biologic processes that involve epigenetic modifications such as transcription, imprinting, mitosis and cellular transformation.

Scientific Focus Areas:
Cancer Biology, Chromosome Biology, Developmental Biology, Stem Cell Biology

Publications

View Dr. Muegge's PubMed Summary.

Selected Key Publications
  1. Tao Y, Xi S, Shan J, Maunakea A, Che A, Briones V, Lee EY, Geiman T, Huang J, Stephens R, Leighty RM, Zhao K, Muegge K.
    Proc Natl Acad Sci U S A. 108: 5626-31, 2011. [ Journal Article ]
  2. Tao Y, Liu S, Briones V, Geiman TM, Muegge K
    Nucleic Acids Res. 39: 9508-20, 2011. [ Journal Article ]
  3. von Eyss B, Maaskola J, Memczak S, Möllmann K, Schuetz A, Loddenkemper C, Tanh MD, Otto A, Muegge K, Heinemann U, Rajewsky N, Ziebold U.
    EMBO J. 31: 972-85, 2012. [ Journal Article ]
  4. Yu W, Briones V, Lister R, McIntosh C, Han Y, Lee EY, Ren J, Terashima M, Leighty RM, Ecker JR, Muegge K.
    Proc Natl Acad Sci U S A. 111: 5890-5, 2014. [ Journal Article ]
  5. Yu W, McIntosh C, Lister R, Zhu I, Han Y, Ren J , Landsman D, Lee E, Briones V, Terashima M, Leighty R, Ecker JR, Muegge K
    Genome Res. 24: 1613-23, 2014. [ Journal Article ]

Biography

Dr. Muegge obtained her M.D. degree at the Medical School Hannover, Germany. During her postdoctoral period she worked on cytokines and T cell development in the Laboratory of Molecular Immunoregulation of Dr. Joost Oppenheim and Dr. Scott Durum. As a Principal Investigator at the National Cancer Institute in Frederick, she now investigates in the Laboratory of Cancer Prevention chromatin organization during embryonic development and in tumor progression.

Team

Name Position
Samantha Barbour Postbaccalaureate Fellow
Yixing Han Postdoctoral Fellow (Visiting)
Jianke Ren Postdoctoral Fellow (Visiting)
Weishi Yu Ph.D. Postdoctoral Fellow (Visiting)