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Nathan Witmer

Address: 4400K PBDBNathan Witmer photo
Phone: (319) 353-5573
Email: nathan-witmer@uiowa.edu

Mentor: Ryan Boudreau, PhD

Undergraduate Institution:

Graduate Program: Molecular Medicine

Year entered into Program: 2019

Research Description

Characterizing Novel Mitochondrial Microproteins in Cardiac Disease

Emerging data indicate we have underestimated the number of unique proteins encoded by our genome due to misconceptions about how big proteins need to be in order to serve a cellular purpose; only ORFs containing >100 amino acids were annotated. Ribosome profiling, an approach that maps actively translating ribosomes at sub-codon resolution, has recently been utilized to reveal short open reading frames (sORFs) that encode microproteins (MPs; proteins of less than 100 amino acids). Recently, bioinformatic studies have shown that the mitochondrial proteome is enriched in MPs. During heart failure, the deterioration of cardiac function coincides with decreased mitochondrial function and serve as attractive targets for therapeutic pharmacological intervention. The goal of this study is to characterize the impact of several novel MPs on mitochondrial function in vitro for future in vivo studies in murine cardiac disease models. Thus far, I have cloned epitope-tagged expression constructs, confirmed mitochondrial localization, begun basic mitochondrial phenotyping assays (mitochondrial membrane potential and mitochondrial ROS production), and analyzed bioinformatic data (RNA-seq, Ribo-seq, co-expression, etc.) to look for connections to cardiac disease states.

Awards

  • Predoctoral Training Grant in the Pharmacological Sciences (T32 GM067795), 2020-present
  • Molecular Medicine Retreat Poster Presentation Award, Sept 2020

Publications

  1. Stein CS, McLendon JM, Witmer NH, and Boudreau RL.:  Modulation of miR-181 influences dopaminergic neuronal degeneration in a mouse model of Parkinson’s disease. EMBO Molecular Medicine. Nearing submission
  2. Stein CS, Jadiya P, Zhang X, McLendon JM, Abouassaly GM, Witmer NH, Anderson EJ, Elrod JW, Boudreau RL.:  Mitoregulin: A lncRNA-Encoded Microprotein that Supports Mitochondrial Supercomplexes and Respiratory Efficiency. Cell Reports, 23(13):3710-3720.e8, 2018.  PMCID: PMC6091870

 

Research