Christopher R. Cederroth received his Ph.D. degree in 2009 from the University of Geneva, Switzerland. In the laboratory of Prof. Serge Nef, he investigated the molecular mechanisms of endocrine disruption by xenoestrogens on sexual development, reproduction and metabolism. His Ph.D. work was awarded the Denber-Pinard Prize from the University of Geneva and led to the creation of a start-up company in the medical food sector, named Amazentis S.A.
In 2009, he moved to New York City as a Swiss National Foundation Advanced Fellow to initiate at the Rockefeller University in the laboratory of Prof. A. James Hudspeth a study aimed at bringing tinnitus research to mice
In 2012, thanks to the Wenner Gren Stiftelse and the Nicholson Postdoctoral Fellowship initiated by Torsten Wiesel to enhance collaborations between the Rockefeller University and Karolinska Institutet, he joined the laboratory of Prof. Barbara Canlon at the Karolinska Institutet to work on the circadian influence on hearing sensitivity.
Publications in Experimental Audiology
TrkB-mediated protection against circadian sensitivity to noise trauma in the murine cochlea.
Curr. Biol. 2014 Mar;24(6):658-63.
Identification of a Circadian Clock in the Inferior Colliculus and Its Dysregulation by Noise Exposure.
J. Neurosci. 2016 05;36(20):5509-19.
Circadian regulation of auditory function.
Hear. Res. 2017 04;347():47-55.
Differential Phase Arrangement of Cellular Clocks along the Tonotopic Axis of the Mouse Cochlea Ex Vivo.
Curr. Biol. 2017 Sep;27(17):2623-2629.e2.
Dr. Cederroth is now developing an independent axis of research focusing on tinnitus. More precisely, he aims at identifying new factors implicated in acute and chronic tinnitus using a new mouse model and to evaluate the use of an new technology to objectively assess tinnitus in humans.
- 2003, Bachelors Degree (Biological Sciences), University of Geneva, Switzerland
- 2004, Masters Degree (Biological Sciences), University of Geneva, Switzerland
- 2005, Licenciate Degree (Medical Biology), University of Geneva, Switzerland
- 2009, Ph.D. Degree (Sciences), University of Geneva, Switzerland - S. Nef Laboratory
- 2009-2012, Post-doc, Rockefeller University, USA - A. J. Hudspeth Laboratory
- 2012-2014, Post-doc, Karolinska Institutet, Sweden - B. Canlon Laboratory
Description of current research
Hearing deficits are expected to affect 900 million individuals world wide in 2025, three times what is expected for the pandemic diabetes. However, if hearing loss does not kill you, which is probably why we do not talk much about it, it severely affects your daily life being the second cause of “years lived with disability” right after depression and before schizophrenia. One of the most prevalent and distressing symptoms associated with hearing loss is tinnitus, or ringing in the ears, which is defined by the perception of sounds in spite of their physical absence. This condition, which affects about 10-15% of the population, distracts sufferers from work, interferes with concentration and sleep, increases the risk of disability pension and can be so severe as to trigger suicide. Tinnitus, however, is an uncured disorder. Both patients and therapists are highly unsatisfied by the available therapeutic options, and ENTs most often recommend to “live with it”. This is in part due to the lack of fundamental knowledge on the mechanisms causing tinnitus, and those making it persistent.
Hearing loss and tinnitus--are funders and industry listening?
Nat. Biotechnol. 2013 Nov;31(11):972-4.
Our ultimate goal is the prevention and cure of hearing loss and tinnitus. For this purpose, we have established collaborations with the industry to facilitate the translation of our findings into cures. The laboratory focuses on i) the molecular mechanisms that regulate synaptic uncoupling in the ear, ii) the mechanisms that govern homeostatic plasticity in the brain during tinnitus, iii) the causative relationship between peripheral damage and phantom sound generation. We have a dual approach using animal models of hearing loss and tinnitus to decipher the signaling pathways disrupted in the ear and/or in the brain but also using genetics in multi-case families with history of tinnitus, having in aim the identification and validation of new targets for drug development. To address this challenge, we use a battery of techniques including behavior (gap-detection and prepulse inhibition), manganese enhanced MRI, auditory electrophysiology, molecular biology, synaptic histology, cell culture, cytometry, apoptotic assays, mouse genetics, human genetics and epidemiology. In order to assess drug efficacy in humans, we have developed a new technology for the objective measure of tinnitus and are initiating its testing now. We are also actively involved in a worldwide effort to provide international guidelines for clinical trials in tinnitus.
Our research group provides a pre-clinical in vivo screening platform to test drug efficacy for acute or chronic tinnitus. Pharmaceutical companies interested in collaborating with us are welcome to contact us.
Tinnitus development: role of glutamate transporters
Using mouse genetics, we identified a role for glutamate transporters in regulating tinnitus. We are now characterizing the mechanisms by which disruption in glutamate homeostasis causes tinnitus. The main aims are 1) to characterize the functional and molecular consequences of glutamate-mediated de-afferentation in the cochlea. Our working hypothesis is that excess glutamate release in the cochlea causes overexcitation of the auditory neurons, hyperactivate auditory relays, reorganize the auditory cortex and subsequent tinnitus; 2) to determine whether glutamate transporters located in the cochlea or in the brain are the major cause of tinnitus. To test this, pharmacological and genetic approaches (i. loss and ii. gain of function) will differentiate peripheral versus central effects; 3) to determine the key downstream candidate molecules in glutamate-mediated synaptic de-afferentation and tinnitus. The ultimate goal is to provide a better understanding of the ear to brain interactions. These results may have a broad clinical application, contributing to the detailed understanding of normal auditory physiology, as well as the origins of tinnitus resulting from subtle auditory dysfunctions.
GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus.
Front Behav Neurosci 2016 ;10():158.
STOP: Swedish Tinnitus Outreach Project
Tinnitus is a very heterogeneous disorder. Distinct forms of tinnitus cannot respond as well to the same therapeutic intervention. The goals of this study are to identify determinants of tinnitus, and use a comprehensive approach to classify tinnitus patients according to subtypes by means of questionnaires and auditory assessment in order to evaluate the prevalence of each form of tinnitus. In a second step, we want to identify homogeneous sub-groups and perform genetic analyses to define new endophenotypes for a more accurate diagnostic of tinnitus patients at the clinic.
See the Swedish Tinnitus Outreach Project (STOP) webpage for more information.
Genetics of Tinnitus: An Emerging Area for Molecular Diagnosis and Drug Development.
Front Neurosci 2016 ;10():377.
Validation of Online Versions of Tinnitus Questionnaires Translated into Swedish.
Front Aging Neurosci 2016 ;8():272.
Genetic susceptibility to bilateral tinnitus in a Swedish twin cohort.
Genet. Med. 2017 Sep;19(9):1007-1012.
COMIT: Establishment of international Core Outcome Measures In Tinnitus
Within the TINNET consortium, we are working to identify and prioritize core domain sets for tinnitus. A core domain set for tinnitus would be the basic building block for developing a world-wide standardization on outcome measures.
Toward a Global Consensus on Outcome Measures for Clinical Trials in Tinnitus: Report From the First International Meeting of the COMiT Initiative, November 14, 2014, Amsterdam, The Netherlands.
Trends Hear 2015 Apr;19():.
TODD: Tinnitus Objective Diagnostic Device
An important gap in the care of tinnitus patients is the lack of robust objective methodologies to diagnose tinnitus. Through funding of the Swedish Research Council, we have developed such device. The Tinnitus Objective Diagnostic Device is based on gap-detection, a variant of pre-pulse inhibition that is commonly used in humans to diagnose schizophrenia. It consists in measuring the blinking reflex of a subject in response to a short startling stimulus presented within a continuous background noise. In individuals without tinnitus, when a silent gap of short duration precedes the startle stimulus, it acts as a warning system that inhibits the amplitude of the blinking reflex. In tinnitus patients, when the frequency of the background closely matches that of the perceived tinnitus, tinnitus interferes with the perception of the gap and as a consequence the inhibition of the blinking reflex is less efficient. Hence, tinnitus affects gap-detection, which translates in greater startle response than in absence of tinnitus. The study aims at identifying the optimal parameters for gap detection in normal individuals and at determining to which subtypes of tinnitus patients this tool is valid for.
Differential Neural Responses Underlying the Inhibition of the Startle Response by Pre-Pulses or Gaps in Mice.
Front Cell Neurosci 2017 ;11():19.
Research funding - past and present
H2020 ITN (ESIT), Vetenskapsrådet, Lars Hiertas Minne, Magnus Bergvalls Stiftelse, Loo och Hans Ostermans, Tysta Skolan and Karolinska Institutet.
Please contact us if you are willing to support our research.
Our research team works in close co-operation with several national and international researchers and is part of the COST Action TINNET BM1306. Among our partners are experts with extensive experience in pre-clinical clinical auditory research, psychologists, geneticists, chemists, basic molecular biology research and industries. This constellation of researchers enables a deeper understanding of how auditory disorders arise and can be cured.
Follow the progress of our Frontiers Research Topic!
We are looking for neuroscientists, cell biologists, biochemists, epidemiologists, audiologists, mouse geneticists: I strongly encourage scientists to contact me with a letter of interest, CV and letters of recommendation. I would be most happy to help with applications for external support for those eligible for postdoctoral fellowships (e.g. SSMF, Swedish Brain Foundation, Swedish Research Council, HSFP, Wenner Gren Stiftelse).
Academic honours, awards and prizes
- 2014 Assistant Professorship from Karolinska Institutet
- 2014 Excellence in Reviewing in the journal Hearing Research
- 2011 Philippe Foundation Prize (USA)
- 2010 Denber-Pinard Prize (CH)
- 2007 Endocrinology Foundation Prize (CH)