Björn Oettinghaus

Björn Oettinghaus
Roche · Pharma Development Quality Assurance

PhD

About

38
Publications
5,298
Reads
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524
Citations
Introduction
Björn Oettinghaus currently works as a Quality Data Scientist at Roche and has formerly worked in neurobiology and mitochondrial dynamics in academia.
Additional affiliations
June 2014 - present
Universitätsspital Basel
Position
  • PostDoc Position
June 2011 - June 2014
Universitätsspital Basel
Position
  • PhD Student
Description
  • Continuation of the Geneva project
June 2008 - June 2011
University of Geneva
Position
  • PhD Student

Publications

Publications (38)
Article
Full-text available
Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that...
Article
Full-text available
Stress adaptation is essential for neuronal health. While the fundamental role of mitochondria in neuronal development has been demonstrated, it is still not clear how adult neurons respond to alterations in mitochondrial function and how neurons sense, signal, and respond to dysfunction of mitochondria and their interacting organelles. Here, we sh...
Article
During apoptosis mitochondria undergo cristae remodeling and fragmentation, but how the latter relates to outer membrane permeabilization and downstream caspases activation is unclear. Here we show that the mitochondrial fission protein Dynamin Related Protein (Drp) 1 participates in cytochrome c release by selected intrinsic death stimuli. While B...
Article
Full-text available
Research efforts during the last decade have deciphered the basic molecular mechanisms governing mitochondrial fusion and fission. We now know that in mammalian cells mitochondrial fission is mediated by the large GTPase dynamin-related protein 1 (Drp1) acting in concert with outer mitochondrial membrane (OMM) proteins such as Fis1, Mff, and Mief1....
Article
Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vit...
Article
Background - As investigator site audits have largely been conducted remotely during the COVID-19 pandemic, remote quality monitoring has gained some momentum. To further facilitate the conduct of remote quality assurance (QA) activities for clinical trials, we developed new quality indicators, building on a previously published statistical modelin...
Article
Full-text available
Translational errors frequently arise during protein synthesis, producing misfolded and dysfunctional proteins. Chronic stress resulting from translation errors may be particularly relevant in tissues that must synthesize and secrete large amounts of secretory proteins. Here, we studied the proteostasis networks in the liver of mice that express th...
Article
Full-text available
Clinical drug development is a complex and extensive process that entails multiple stakeholders alongside patients, requires large capital expenditures and takes nearly a decade on average to complete. To ensure the correct development of this process, rigorous quality activities must be conducted to assess and guarantee the Good Clinical and Pharm...
Article
In the majority of cancers, pathogenic variants are only found at the level of the tumor; however, an unusual number of cancers and/or diagnoses at an early age in a single family may suggest a genetic predisposition. Predisposition plays a major role in about 5-10% of adult cancers and in certain childhood tumors. As access to genomic testing for...
Preprint
Full-text available
Background - As investigator site audits have largely been conducted remotely during the COVID-19 pandemic, remote quality monitoring has gained some momentum. To further facilitate the conduct of remote Quality Assurance (QA) activities for clinical trials, we developed new quality indicators, building on a previously published statistical modelin...
Presentation
Full-text available
The recent COVID-19 pandemic has changed clinical quality assurance as access to investigator sites became limited, resulting in an increase of remote quality activities. Here we provide an overview of how we are using advanced data analytics to support remote quality activities at Roche.
Preprint
Full-text available
In the majority of cancers, pathogenic variants are only found at the level of the tumor; however, an unusual number of cancers and/or diagnoses at an early age in a single family may suggest a genetic predisposition. Predisposition plays a major role in about 5 to 10% of adult cancers and in certain childhood tumors. As access to genomic testing f...
Preprint
Full-text available
Clinical drug development is a complex and extensive process that entails multiple stakeholders alongside patients, requires large capital expenditures and takes nearly a decade on average to complete. To ensure the correct development of this process, rigorous quality activities must be conducted to assess and guarantee the Good Clinical and Pharm...
Article
Full-text available
The world has seen a shift in the ways of working during the Covid-19 pandemic. Routine activities performed at the clinical investigator sites (e.g. on-site audits) that are a part of Quality Assurance (QA) have not been feasible at this time. Analytics has played a huge role in contributing to our continued efforts of ensuring quality during the...
Article
In a previous project, we developed a predictive model that enables Roche Quality Program Leads oversight of adverse event (AE) reporting by investigator sites during clinical trials. Subsequently, we provided evidence to validate our model using external clinical trial datasets. At that time, we used historical data and could not include study-sit...
Code
Monitoring of Adverse Event (AE) reporting in clinical trials is important for patient safety. We use bootstrap-based simulation to assign an AE under-reporting probability to each site in a clinical trial. The method is inspired by the ‘infer’ R package and Allen Downey’s blog article: “There is only one test!”.
Article
Full-text available
We set-up an interactive dashboard to derive insights from the FDA Clinical Inspections database. This dashboard is open access and meant to be used by clinical quality professionals. https://erblast.github.io/fda_inspections/
Article
Full-text available
Background The increasing number of clinical trials and their complexity make it challenging to detect and identify clinical quality issues timely. Despite extensive sponsor audit programs and monitoring activities, issues related to data integrity, safety, sponsor oversight and patient consent have recurring audit and inspection findings. Recent...
Data
In this ESM document we provided a detailed list of features and how they were used (Table 1). The coefficients and AUC values of the time series cross validation iterations (Figure 1) and an overview of the distribution of missing data in our data set (Figure 2).
Code
We set-up an interactive dashboard to derive insights from the FDA Clinical Inspections database. This dashboard is open access and meant to be used by clinical quality professionals.
Article
Full-text available
In a previous project, we developed a predictive model that enabled Roche/Genentech quality leads oversight of adverse event (AE) reporting. External clinical trial datasets such as Project Data Sphere allowed us to further test our machine learning-based approach to alleviate concerns of overfitting and to demonstrate the reproducibility of our re...
Article
Full-text available
Introduction Adverse event (AE) under-reporting has been a recurrent issue raised during health authorities Good Clinical Practices (GCP) inspections and audits. Moreover, safety under-reporting poses a risk to patient safety and data integrity. The current clinical Quality Assurance (QA) practices used to detect AE under-reporting rely heavily on...
Data
Electronic Supplementary Material #3 ­ List of formulas
Article
Full-text available
The 1555 A to G substitution in mitochondrial 12S A-site rRNA is associated with maternally transmitted deafness of variable penetrance in the absence of otherwise overt disease. Here, we recapitulate the suggested A1555G-mediated pathomechanism in an experimental model of mitoribosomal mistranslation by directed mutagenesis of mitoribosomal protei...
Article
Pharmacological inhibition of dynamin-related protein 1 (Drp1) the main mammalian promoter of mitochondrial fission - has emerged as a promising therapeutic target for the treatment of neuronal injuries. Genetic studies, however, have revealed that inhibiting Drp1 during development leads to defects especially in neuronal differentiation. Bypassing...
Article
Full-text available
The apoptotic protease activating factor 1 (Apaf1) is the main component of the apoptosome, and a crucial factor in the mitochondria-dependent death pathway. Here we show that Apaf1 plays a role in regulating centrosome maturation. By analyzing Apaf1-depleted cells, we have found that Apaf1 loss induces centrosome defects that impair centrosomal mi...
Article
Full-text available
Antibiotics targeting the bacterial ribosome typically bind to highly conserved rRNA regions with only minor phylogenetic sequence variations. It is unclear whether these sequence variations affect antibiotic susceptibility or resistance development. To address this question, we have investigated the drug binding pockets of aminoglycosides and macr...
Article
Full-text available
Apoptosis is a type of programmed cell death (PCD) conserved among metazoans and crucial for the development and homeostasis of tissues in multicellular organisms. Lower unicellular eukaryotes like yeast would thus have no need for it and they apparently lack the key regulators of mitochondria-dependent apoptosis. In this issue, Buttner et al (2011...

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Projects

Projects (3)
Project
Define strategy and methods for AI/ML quality (incl. validation) in the genomics and RWD space
Project
propose new approaches and innovation in clinical safety and PV
Project
demonstrate the value of advanced analytics to early detect and mitigate clinical quality issues - in order to speed up clinical trial execution, enhance patient safety and ensure data integrity in GCP/PV