Pagliarini


Email

441B Biochemistry Laboratories
433 Babcock Drive
Madison, WI 53706-1544
USA

(608) 890-3254

   

David J Pagliarini

           

Assistant Professor
B.S.: University of Notre Dame
Ph.D.: University of California, San Diego
Postdoc: Harvard Medical School

For more information on the Pagliarini Lab, please visit our lab website: www.pagliarinilab.org

      

Mitochondrial biogenesis and metabolism; cell signaling; proteomics


Three mitochondria images
PDF
Mitochondria are complex organelles whose dysfunction underlies a broad spectrum of human diseases. Mitochondria house a wide range of metabolic pathways and are central to apoptosis and reactive oxygen species production. Thus, to maintain cellular homeostasis cells must exert careful control over their mitochondrial composition and function.

How do cells custom-build mitochondria to suit their metabolic needs? What mechanisms do cells leverage to efficiently control mitochondrial processes? Which mitochondrial processes are disrupted in diseases and how might these be targeted therapeutically?

Our lab takes a multi-disciplinary approach to investigating these questions. By integrating classic biochemistry, molecular biology and genetics with large-scale proteomics and systems approaches, we aim to elucidate how cells regulate mitochondrial metabolism and establish a customized mitochondrial infrastructure across tissues and in response to a changing cellular environment. Below are current focuses of our lab.

uORF diagram
Post-transcriptional control of gene expression

Post-transcriptional regulatory processes are becoming increasingly appreciated as a means of controlling the efficiency, timing, location, and tissue specificity of gene expression. We leverage quantitative proteomics and expression profiling to identify genes subject to regulation at the mRNA level. In particular, we focus on elements in the untranslated regions (UTR) of mRNA that are involved in titrating the expression of mitochondrial proteins. PDF

Molecular Cell cover
Regulation of mitochondrial function by post-translational modifications

While transcriptional and post-transcriptional processes are instrumental to mitochondrial biogenesis and restructuring, real-time regulation of protein function is generally carried out by post-translational modifications (PTMs). Much of the mitochondrial proteome is modified by PTMs such as phosphorylation and acetylation, but the proteins responsible for these modifications and their roles in regulating mitochondrial function are largely unknown. We combine molecular biology and proteomics to match mitochondrial signaling molecules with their substrates, and to explore how the cell uses PTMs to control mitochondrial function in response to cellular stresses such as hypoxia, nutrient deprivation and inflammation.
 

Comparative mitochondrial proteomics of healthy and disease states


Faulty mitochondrial function has been implicated in ~50 monogenic disorders, and growing evidence suggests it is also a major contributor to a range of common diseases. Most notably, mitochondrial dysfunction is a central theme of type 2 diabetes mellitus (T2DM), which currently affects more than 20 million individuals in the US alone. However, the specific mitochondrial alterations that appear to play a role in the development of T2DM remain poorly defined. In collaboration with Alan Attie and Josh Coon, we are applying state-of-the-art quantitative mass spectrometry to produce a map of proteome and phospho-proteome alterations in mitochondria during the onset of diabetes.
 
 Comparative proteomics diagram

Control of OXPHOS function and assembly

Oxidative phosphorylation (OXPHOS) is the engine that drives the bulk of ATP production in cells, and OXPHOS disorders are the most common group of inborn errors of metabolism. An array of gene mutations that give rise to OXPHOS disorders have been identified through human genetics, but many of these genes encode proteins of no known function. We use mitochondrial physiology and biochemistry to explore the role of these proteins in the proper assembly and function of the OXPHOS complexes, with the ultimate goal of identifying promising therapeutic targets for mitochondrial diseases.
 Oxidative phosphorylation diagram
PDF


    

 

 

Copyright 2014 – This page last modified 9/7/2011

Website Feedback, questions or other issues