The cell nucleus surrounds, organizes and mechanically protects the genome. Lamin filament networks and nuclear membrane proteins support and influence most activities in the nucleus, with central and dynamic roles in customizing the 3D spatial organization of individual chromosomes needed for tissue-specific gene silencing. The functions and regulation of nuclear ‘lamina’ networks are an open frontier in biology.
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Katherine (Kathy) Wilson, Ph.D.
Katherine (Kathy) Wilson, Ph.D.website
Department of Cell Biology
Johns Hopkins University School of Medicine
725 N. Wolfe Street, G10 WBSB
Baltimore, MD 21205
Within each human cell is a NUCLEUS, 'mothership' of the human genome and still the least-understood cellular structure. Chromosomes are enclosed by the nuclear envelope (NE) and communicate with the cytoplasm through Nuclear Pore Complexes (NPCs). The inner and outer membranes of the NE are mechanically connected by SUN-domain proteins and nesprins, which form LINC (links the nucleoskeleton and cytoskeleton) complexes. LINC complexes are anchored to nuclear intermediate filament (nuclear ‘lamina’) networks. Together the NE and nuclear lamina protect, organize and help regulate chromatin.
Research in the Wilson lab centers on the three key components of nuclear lamina structure: lamins (encoded by LMNA, LMNB1, LMNB2), LEM-domain proteins (e.g., emerin, encoded by EMD), and BAF (Barrier to autointegration factor, encoded by BANF1). These proteins all bind each other directly, and are collectively required to organize and regulate chromatin, efficiently segregate chromosomes and rebuild nuclear structure after mitosis. Mutations in these proteins cause human ‘laminopathy’ diseases including Emery-Dreifuss muscular dystrophy (EDMD), cardiomyopathy, neuropathy, ‘accelerated aging’ (progeria syndromes), lipodystrophy/diabetes and metabolic syndrome. These disease mechanisms are not understood.
Current work aims to understand the molecular mechanisms of emerin function at the nuclear envelope, emerin molecular attachments to BAF/chromatin and lamin filaments, and how these interactions are controlled by metabolic status (O-GlcNAc cycle), phosphorylation, mechanical force and cell signaling.
Recent Lab Members Include:
Jason Berk, Ph.D.
Postdoctoral Fellow w/Mark Hochstrasser
Ph.D. Student at UMBC
Dan Simon, Ph.D.
Postdoctoral Fellow w/Michael Rout