Ulla Pirvola - Physiology and neuroscience

Fig: The auditory sensory epithelium. Anna Kirjavainen, 2014.
  Fig: The auditory sensory epithelium. Anna Kirjavainen, 2014.

 

Cellular development, repair and protection in the auditory organ – from basic science to translational research

Ulla Pirvola, PhD,
University Lecturer, Group leader

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The sensory cells of the auditory organ, the hair cells and the innervating neurons, are responsible for mechanotransduction and encoding of sound information. These cells are born during embryogenesis. The same cells are responsible for hearing function during the whole lifetime. Hair cells and neurons are easily damaged by factors such as noise, certain drugs and the effects of aging. Loss of these cells leads to permanent hearing impairment, since they do not regenerate in mammals. Hearing loss is a very common disability in humans. Due to the lack of good medical treatment, the main part of the affected population goes currently untreated. Understanding the mechanisms how the sensory cells develop and how they and other cell types of the hearing organ respond to stress allows the development of therapeutic interventions to treat hearing impairment.

Fig: 3D reconstruction of an auditory hair cell. Tommi Anttonen, 2014.

We study the regulation of inner ear development. We have recently shown the importance of the GTPase Cdc42 in cytoskeletal development and planar cell polarity in the cells of the auditory organ. These in vivo studies used novel mutant mouse models and high-resolution confocal and electron microscopical imaging.

We study the regeneration capacity of the cells of the inner ear. We have recently shown that DNA damage and limited DNA repair capacity critically limit the attempts to stimulate regeneration of supporting cells, the cells that serve as a potential platform for new hair cell formation. This study used organotypic explant culturing and viral-mediated gene transfer.

We study the mechanisms of hair cell death and repair (wound healing) of the damaged auditory organ. We have used a novel method, serial block-face scanning electron microscopy, allowing 3D modeling at subcellular level of the auditory organ. Using this method, we have recently described the modes of hair cell death and the process of wound healing performed by supporting cells.

Our goal is to find pharmacological methods to protect hair cells from noise trauma, the most common cause of hearing impairment. We have recently shown the mechanisms how the JNK/c-Jun stress signaling pathway mediates hair cell death following traumas. We have provided genetic and pharmacological evidence that inhibition of this signaling attenuates noise-induced hair cell loss.

Fig: 3D reconstruction of an auditory hair cell. Tommi Anttonen, 2014.

 


Selected publications | More publications >>

Anttonen T*, Herranen A*, Laos M, Elomaa P, Kirjavainen A, Virkkala J, Behrens A, Pirvola U (2016) c-Jun N-terminal Phosphorylation: Biomarker for Cellular Stress rather than Cell Death in the Injured Cochlea. eNeuro DOI: 10.1523/ENEURO.0047-16.2016

Kirjavainen A, Laos M, Anttonen T, Pirvola U (2015) The Rho GTPase Cdc42 regulates hair cell planar polarity and cellular patterning in the developing cochlea. Biol Open 4, 516-526.

Anttonen T, Belevich I, Kirjavainen A, Laos M, Brakebusch C, Jokitalo, Pirvola U (2014) How to Bury the Dead: Elimination of Apoptotic Hair Cells from the Hearing Organ of the Mouse. JARO 15, 975-992.

Laos M, Anttonen T, Kirjavainen A, af Hällström T, Laiho M, Pirvola U (2014) DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells. Aging 6, 496-510.

Anttonen T*, Kirjavainen A*, Belevich I, Laos M, Ylikoski J, Richardson WD, Jokitalo E, Brakebusch C, Pirvola U (2012). Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood. Sci Rep 2, 978.

Fig: DNA damage foci in the nuclei of cell cycle reactivated supporting cells. Maarja Laos, 2014

Fig: DNA damage foci in the nuclei of cell cycle reactivated supporting cells. Maarja Laos, 2014