HughesLab:Open Positions

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Pre- or Post-doctoral Associate -- Study of Muscle Mobility and Aging (SOMMA)

The Hughes Lab is located in the Division of Pulmonary and Critical Care Medicine at Washington University in St. Louis. We are seeking talented applicants for a pre- or post-doctoral position studying the effects of aging on skeletal muscle and mobility disability.

In collaboration with the Study of Muscle Mobility and Aging (SOMMA), we will use RNA-sequencing to profile gene expression in several hundred skeletal muscle biopsies from subjects aged 70 years and older. We therefore have access to a new and unique dataset describing the physiological changes associated with aging. Consortium members will (1) identify subjects who develop mobility disability during the five year term of this project, (2) measure mitochondrial function from the same biopsies, (3) measure autophagic flux and protein turnover, and (4) use MRI imaging to measure structural changes in muscle. Ancillary studies will measure metabolism in white fat and gene expression changes in blood cells. In short, this is a data gold mine, and we have the opportunity to use these resources in combination with machine learning to identify gene expression markers and putative molecular mechanisms underlying muscle aging with direct implications for human health.

Salary will be commensurate with qualifications and experience. The strongest candidates will have experience in some combination of skeletal muscle biology, bioinformatics, and human genetics. Candidates should apply by emailing their cover letter, curriculum vitae, and the names of three references to Dr. Michael Hughes: michael.hughes@wustl.edu.

Minimum qualifications:
• PhD or equivalent in Biomedical sciences or admission to the DBBS program at Washington University
• Comfort and experience working with molecular biology and genetics

Knowledge, Skills, and Abilities:
• Bioinformatics, R, SQL, Python, etc.
• Fluency in molecular biology and genetics
• Ability to work well in a team of scientists from diverse backgrounds


Pre- or Post-doctoral Associate -- RNA Editing in muscle development and function

The Hughes Lab is located in the Division of Pulmonary and Critical Care Medicine at Washington University in St. Louis. We are seeking talented applicants for a pre-or post-doctoral position studying the effects of RNA editing on skeletal muscle.

We have demonstrated that Adar genes are expressed in all adult skeletal muscles, and that RNA editing sites are present in hundreds of key muscle genes, including structural components of the sarcomere, ion channels, and proteins involved in myokine signaling. RNA editing sites are more common in soleus than in EDL tissues, suggesting tissue-specificity in editing profiles. Consistent with this, the biased expression of the ratio of Adar:Aimp2 indicates that differences between slow- and fast-twitch muscle fibers may be due to differential RNA editing frequencies. Based on these preliminary studies, we hypothesize that RNA editing is common and physiologically significant in adult skeletal muscle. To further develop this line of investigation, we propose several specific mechanistic hypotheses, including the possibility that slow-twitch fibers have de-repressed Adar activity due to a relatively low Aimp2 expression. To test these hypotheses, we offer the following specific aims: (1) Using in silico approaches, determine whether RNA editing influences skeletal muscle specialization, (2) Using in vitro cell culture, test whether muscle-specific trans factors regulate RNA editing, and (3) Using in vivo models, test whether RNA editing regulates sarcomere function. These aims make use of the relative strengths of three independent methodologies to test the overall hypothesis that RNA editing is physiologically significant in mature skeletal muscle. Data mining will be used to compare systematically RNA editing frequencies in many different muscle tissues and disease states. Cell culture will be used to screen rapidly candidate factors that may regulate editing specifically in skeletal muscle. Tissue-specific mouse mutants will be used to circumvent the technical limitations of Adar knock-out mice and thereby test the effects of RNA editing in sarcomere function in adult tissues. All three aims are technically independent and mutually reinforcing. Successful completion of this research proposal will provide the first ever detailed understanding of the prevalence, significance, and regulation of RNA editing in adult skeletal muscle tissues. More broadly, it will lay the foundation for mechanistic studies into an entirely novel mechanism by which normal physiology and disease may be manipulated in skeletal muscle. The scientist pursuing this line of investigation will have a unique dataset on Day 1, and the potential to identify and explore a heretofore unexplored aspect of post-transcriptional regulation in muscle.

Salary will be commensurate with qualifications and experience. The strongest candidates will have experience in some combination of skeletal muscle biology, bioinformatics, and mouse genetics. Candidates should apply by emailing their cover letter, curriculum vitae, and the names of three references to Dr. Michael Hughes: michael.hughes@wustl.edu.

Minimum qualifications:
• PhD or equivalent in Biomedical sciences
• Comfort and experience working with laboratory mice

Knowledge, Skills, and Abilities:
• Bioinformatics, R, SQL, Python, etc.
• Fluency in molecular biology and mouse genetics
• Ability to work well in a team of scientists from diverse backgrounds


Postdoctoral Associate -- Muscle Wasting in COPD

Postdoctoral Associate in the Department of Medicine at Washington University
The Hughes Lab is located in the Division of Pulmonary and Critical Care Medicine at Washington University in St. Louis. We are seeking talented applicants for a postdoctoral position studying the effects of systemic inflammation on skeletal muscle.

Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the United States, and its extra-pulmonary manifestations are a shockingly under-studied contributor to morbidity and mortality. Our lab has recently published (Terry et al. (2018) eLife) the definitive resource of gene expression in skeletal muscle (http://muscledb.org). With these data as a foundation, we are now using functional genomics approaches to study how skeletal muscle reacts to pulmonary disease. We have established a pre-clinical mouse model that recapitulates muscle atrophy due to COPD. Our current projects focus on identifying the cells, genes, and signaling pathways that govern reciprocal interactions between the lungs and muscle. Our long-term goal is to manipulate skeletal muscle for the betterment of human COPD patients. These projects will require the effective use of pre-clinical mouse models, RNAseq, single-cell RNAseq, muscle physiology and histology, and the analysis of human clinical samples.

Salary will be commensurate with qualifications and experience. The strongest candidates will have experience in some combination of skeletal muscle biology, bioinformatics, and mouse genetics. Candidates should apply by emailing their cover letter, curriculum vitae, and the names of three references to Dr. Michael Hughes: michael.hughes@wustl.edu.

Minimum qualifications:
• PhD or equivalent in Biomedical sciences or admission to the DBBS program at Washington University
• Comfort and experience working with molecular biology

Knowledge, Skills, and Abilities:
• Bioinformatics, R, SQL, Python, etc.
• Fluency in molecular biology and genetics
• Ability to work well in a team of scientists from diverse backgrounds


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