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John D. Lueck, Ph.D.

Contact Information

Phone Numbers

Office: (585) 276-5489

Fax: (585) 273-2652

Research Labs

Faculty Appointments

Biography

Professional Background

The focus of my research is to evaluate the therapeutic promise of suppressor tRNA for treatment of cystic fibrosis. In my graduate training I studied myotonia in myotonic dystrophy type 1 (DM1) in Dr. Robert Dirksen’s laboratory and in collaboration with Dr. Charles Thornton. I used both molecular biology/genetics and electrophysiology approaches to determine how the DM1-associated problems with alternative splicing affect function of ClC-1 chloride channel and muscle excitability. I showed that chloride conductance is rapidly rescued if ClC-1 splicing is corrected or if sequestration of splicing factors is released. I also investigated the effects of splicing misregulation on function of RyR1. These studies resulted in 10 publications and cemented my interest in doing translational research. Following my graduate work, I joined Dr. Kevin Campbell’s laboratory. There I learned membrane protein biochemistry, antibody generation and testing mouse skeletal muscle physiology testing and gene therapy approaches, in studies focused on muscular dystrophy. This experience makes me well suited to conduct independent research using a breadth of techniques focused disease pathogenesis. My research took a turn as I became interested in the field of genetic code expansion and its use as a therapeutic for cystic fibrosis (CF) that result from nonsense mutations. I quickly published 5 studies in 3 years with Dr. Chris Ahern that propelled me to my current independent position, where I have been able to extend my research in determining the therapeutic promise of our suppressor tRNA technologies for CF. In my next steps, I will use my extensive training in mouse genetics, molecular biology, membrane biophysics and protein biochemistry to investigate the impact on cellular and tissue processes following stop codon suppression in vivo and generate new CF therapeutic deliverables that can be translated into other nonsense associated diseases. More broadly, I'm interested in applying membrane biophysics and molecular and cellular biology approaches to elucidate the molecular underpinning of genetic diseases, and then using mechanistic insights to develop new treatments.

Research

My research focuses on the molecular genetics and experimental treatment of diseases resulting from nonsense mutations. I am investigating the use of engineered tRNAs for suppression of nonsense mutations in cystic fibrosis transmembrane conductance regulator (CFTR) transcripts as therapeutic intervention for cystic fibrosis. Additionally, I am interested in the molecular genetics and experimental treatment of the trinucleotide repeat disorder myotonic dystrophy (DM1). Moving forward, I intend to study pre-mRNA splicing defects in DM1 to determine the causes of muscle weakness and wasting, and develop and test new therapeutic strategies to target the genetic misstep and reverse symptoms. More broadly, I'm interested in applying membrane biophysics, molecular and cellular biology approaches to understand the molecular underpinning of genetic diseases and develop therapeutic interventions.

Publications

Journal Articles

2/7/2020
Rook ML, Williamson A, Lueck JD, Musgaard M, Maclean DM. "?11-12 linker isomerization governs acid-sensing ion channel desensitization and recovery." eLife.. 2020 Feb 7; 9Epub 2020 Feb 07.

2/18/2019
Lueck JD, Yoon JS, Perales-Puchalt A, Mackey AL, Infield DT, Behlke MA, Pope MR, Weiner DB, Skach WR, McCray PB, Ahern CA. "Engineered transfer RNAs for suppression of premature termination codons." Nature communications.. 2019 Feb 18; 10(1):822. Epub 2019 Feb 18.

4/6/2018
Molinarolo S, Lee S, Leisle L, Lueck JD, Granata D, Carnevale V, Ahern CA. "Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel." The Journal of biological chemistry.. 2018 Apr 6; 293(14):4981-4992. Epub 2018 Jan 25.

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