Sensory biology and neurobiology of the auditory system – from basic research to biomedical applications

Organisational unit: Research Group

Organisation Profile

SENSORY BIOLOGY AND NEUROBIOLOGY OF THE AUDITORY SYSTEM – FROM BASIC RESEARCH TO BIOMEDICAL APPLICATIONS

 

RESEARCH

Our research examines the mechanisms regulating development, regeneration and repair of the cells of the auditory system. Currently, we focus on the pathophysiology of the auditory organ and the brain auditory network following exposure to loud sounds. We believe that this understanding allows the design of interventions to fight against noise-induced hearing impairment. These interventions could also be effective against the disorders of the central auditory disorders.

Our experimental approach involves in vivo functional assays, use of transgenic mouse models, analysis gene and protein expression, versatile microscopic imaging, and organ cultures coupled with viral-mediated gene transfer.

DEVELOPMENT: We have recently shown that the GTPases Cdc42 and RhoA are required for planar cell polarity and normal cytoskeletal development of hair cells and supporting cells of the cochlea. These studies were done using transgenic mouse models in vivo (Anttonen et al., 2012, 2017; Kirjavainen et al., 2015).

REPAIR: We have recently described the modes of hair cell death and the mechanisms of actin cytoskeleton-based wound healing in the organ of Corti of the cochlea, using serial block-face scanning electron microscopy (SBEM). This method is very suitable for 3D subcellular modelling of the organ of Corti (Anttonen et al. 2014, 2017).

REGENERATION: We have recently studied the regeneration capacity of the inner ear supporting cells, the cells that serve as a potential platform for new hair cell formation. We have shown that DNA damage and limited DNA repair capacity form a challenging barrier for the attempts to stimulate supporting cell proliferation, particularly in the adult cochlea. These studies were done using viral-mediated gene transfer in organ cultures and the analysis of transgenic mouse models in vitro and in vivo (Mdm2, p53) (Laos et al., 2014, 2017).

STRESS SIGNALING: We have recently shown the mode of action of JNK/c-Jun stress signaling in the lesioned cochlea. We have provided genetic and pharmacological evidence that inhibition of this signaling attenuates hair cell loss following noise exposure (Anttonen, Herranen et al., 2016). Most recently, we have studied the role of JNK/c-Jun, ERK and NF-kB stress pathways in the lateral wall of the cochlea. We have implicated their role in inflammation, in the sensitivity of hair cells to loud sounds and in aging (Herranen et al. JARO 2018, in press).

CURRENTLY: In our current research, we study the proteostasis control of cell function and survival in the auditory system, both in the peripheral and central pathway, and in basal conditions and following trauma. In the other project, we study how metabolic disturbances affect the function and survival of auditory cells.

 

GROUP LEADER

Ulla Pirvola, PhD, Adjunct Prof.

Molecular and Integrative Biosciences Research Programme

University of Helsinki

 

P.O. Box 65 (Viikinkaari 1),

00014 University of Helsinki

Finland
Phone +358 44 5384409
E-mail ulla.pirvola@helsinki.fi

 

GROUP MEMBERS

Anni Herranen, PhD student

Kuu Ikäheimo, PhD student

graduate students

 

ASSOCIATED TO THE GROUP THROUGH COLLABORATION

Jukka Ylikoski, Prof. & Jarmo Lehtimäki, Helsinki Ear Institute

Jussi Virkkala, PhD, Finnish Institute of Occupational Health

Maria Lindahl, PhD & Mart Saarma, Prof., Inst. of Biotechnology, Univ. of Helsinki

Eija Jokitalo, Prof. & Ilya Belevich, PhD, Inst. of Biotechnology, Univ. of Helsinki

Tommi Anttonen PhD

 

ALUMNI

Tommi Anttonen PhD

Maarja Laos PhD

Anna Kirjavainen PhD

Heidi Loponen PhD

 

RECENT PUBLICATIONS

Herranen A, Ikäheimo K, Virkkala J, Pirvola U (2018) The Acute and Chronic Stress Response in the Non-sensory Cells of the Cochlea – Possible Role in Mediating Noise Vulnerability. J Assoc Res Otolaryngol, in press. doi: 10.1007/s10162-018-0069

Szibor A, Hyvärinen P, Lehtimäki J, Pirvola U, Ylikoski M, Mäkitie A, Aarnisalo A, Ylikoski J (2018) Hearing disorder from music; a neglected dysfunction. Acta Otolaryngol 128:21-24. doi: 10.1080/00016489.2017.1367100

Anttonen T, Belevich Y, Kirjavainen A, Laos M, Herranen A, Jokitalo E, Brakebusch C, Pirvola U (2017) Cytoskeletal stability in the auditory organ in vivo: RhoA is dispensable for wound healing, but essential for hair cell development. eNeuro 4. doi: 10.1523/ENEURO.0149-17.2017

Laos M, Anttonen T, Herranen A, Pirvola U (2017) Indispensable role of Mdm2/p53 interaction during the embryonic and postnatal inner ear development. Sci Rep 7:42216. doi: 10.1038/srep42216

Ylikoski J, Lehtimäki J, Pirvola U, Mäkitie A, Aarnisalo A, Hyvärinen P, Ylikoski M (2017) Non-invasive vagus nerve stimulation reduces sympathetic preponderance in patients with tinnitus. Acta Otolaryngol 137:426-431. doi: 10.1080/00016489.2016.1269197

Anttonen T*, Herranen A*, Virkkala J, Kirjavainen A, Elomaa P, Laos M, Liang X, Ylikoski J, Behrens A, Pirvola U (2016) c-Jun N-Terminal Phosphorylation: Biomarker for cellular stress rather than cell death in the injured cochlea. eNeuro 3. 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. doi:10.1242/bio.20149753

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. J Assoc Res Otolaryngol 15:975-992. doi: 10.1007/s10162-014-0480

Laos M, Anttonen T, Kirjavainen A, af Hällström T, LaihoM, Pirvola U (2014) DNA damage signaling regulates age-dependent proliferative capacity of quiescent inner ear supporting cells. Aging 6:496-510. doi: 10.18632/aging.100668

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. doi: 10.1038/srep00978

 

 

 

Latest research outputs

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