Dave Pagliarini, Ph.D.

Professor
Cell Biology and Physiology
Biochemistry and Molecular Biophysics
Genetics

Biochemistry, Biophysics, and Structural Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Computational and Systems Biology Program

  • 314-273-2331

  • 314-273-2330

  • pagliarini@wustl.edu

  • https://pagliarinilab.org

  • @Pagliarini_Lab

  • Mitochondria, Metabolism, Coenzyme Q, Orphan protein function, Proteomics, Metabolic disease, Systems biochemistry

  • We seek to understand the cellular and biochemical underpinnings of mitochondrial dysfunction in human diseases. Our work integrates large-scale methodologies with traditional biochemistry and cell biology to investigate the modulation, adaptation, and basic metabolic function of mitochondria.

Research Abstract:

Mitochondria are complex and dynamic organelles that are essential to the survival of nearly every eukaryotic cell. The approximately ten million billion mitochondria throughout our bodies produce the bulk of our chemical energy in the form of ATP and are the cellular home to a vast array of essential metabolic pathways and processes.
Dysfunction of these organelles underlies hundreds of inborn errors of metabolism and strongly contributes to a growing list of common metabolic and neurodegenerative disorders, including type II diabetes, Parkinson’s disease, Alzheimer’s disease, and various forms of cancer.

Despite this central role for mitochondria in human health and disease, much of the basic biology of these organelles remains obscure, and therapeutic options to treat mitochondrial dysfunction remain woefully inadequate. By blending classic biochemistry, molecular & cellular biology, and genetics with large-scale proteomics and systems approaches, our lab aims to systematically define the functions of uncharacterized mitochondrial proteins, identify new gene mutations that underlie human disease, and explore new molecular therapeutics to rectify mitochondria-based disorders.

Mentorship and Commitment to Diversity Statement:

As a graduate student mentor, I strive to assist students in choosing thesis work that is meaningful, feasible, and impactful; to empower students to engage in cutting-edge research by guiding their experimental approach, providing ample financial resources, and enriching their graduation education through collaborations and meetings; to provide a healthy and supportive laboratory community where they can grow and develop as scientists; to teach students how to think clearly about science and to communicate their work in a lucid, compelling manner; to assist students in achieving their stated career goals and, when possible, to inform them of viable career options in academia and beyond.

In building a vibrant research team, I strive to instill a culture where all students feel valued, appreciated, and free to be who they are. I believe that preventing discrimination against our students—whether that be based in gender identity, sexual orientation, religion, ethnicity, age, neurodiversity, disability status, citizenship, or any other aspect which makes them unique—is not only a moral imperative, but a route to discovery. Our group adopts a philosophy that diversity drives innovation. We therefore celebrate multiple approaches and points of view, and embrace a culture where difference is valued.

Selected Publications:

Pptc7 is an essential phosphatase that promotes mitochondrial metabolism by enabling protein import and processing
Niemi NM, Wilson GM, Overmyer KA, Vögtle FN, Lohman DC, Schueler KL, Attie AD, Meisinger C, Coon JJ, and Pagliarini DJ
Nature Communications, 2019 10: 3197

An isoprene lipid binding protein promotes eukaryotic coenzyme Q biosynthesis
Lohman DC*, Aydin D*, Von Bank H, Smith R, Linke V, Weisenhorn EM, McDevitt MT, Hutchins PD, Wilkerson EM, Wancewicz B, Russell JD, Stefely MS, Beebe ET, Jochem A, Coon JJ, Bingman CA, Dal Peraro M†, and Pagliarini DJ†
Molecular Cell, 2019 73(4):763-774

Multi-omics reveal specific targets of the RNA-binding protein Puf3p and its orchestration of mitochondrial biogenesis
Lapointe CP*, Stefely JA*, Jochem A, Hutchins PD, Wilson GM, Kwiecien NW, Coon JJ, Wickens MP†, and Pagliarini DJ†
Cell Systems, 2018 6(1):125-135

Conserved lipid and small molecule modulation of COQ8 reveals regulation of the ancient kinase-like UbiB family
Reidenbach AG, Kemmerer ZA, Aydin D, Jochem A, McDevitt MT, Hutchins PD, Stark JL, Stefely JA, Reddy T, Hebert AS, Wilkerson EM, JA, Johnson IE, Bingman CA, Markley JL, Coon JJ, Dal Peraro M, and Pagliarini DJ
Cell Chemical Biology, 2018 25(2):154-165

Multi-omic mitoprotease profiling defines a role for Oct1p in coenzyme Q production
Veling MT, Reidenbach AG, Freiberger EC, Kwiecien NW, Hutchins PD, Drahnak MJ, Jochem A, Ulbrich A, Rush JPR, Russell JD, Coon JJ, and Pagliarini DJ
Molecular Cell, 2017 68(5):970-977

Mitochondrial protein functions elucidated by global mass spectrometry profiling
Stefely JA*, Kwiecien NW*, Freiberger E, Richards AL, Jochem A, Rush MJP, Ulbrich A, Robinson KP, Hutchins PD, Veling MT, Guo X, Kemmerer ZA, Connors KJ, Trujillo EA, Sokol J, Westphall MW, Hebert AS, Pagliarini DJ†, and Coon JJ†
Nature Biotechnology, 2016 34(11):1191-1197

Iron Deprivation Induces Transcriptional Regulation of Mitochondrial Biogenesis
Rensvold JW, Krautkramer KA, Dowell JA, Denu JM, and Pagliarini DJ
Journal of Biological Chemistry, 2016 291(40):20827-20837

Mitochondrial protein interaction mapping identifies new regulators of respiratory chain function
Floyd BJ*, Wilkerson EM*, Veling MT*, Minogue CE*, Xia C, Beebe ET, Wrobel, RL, Cho H, Kremer LS, Alston CL, Gromek KA, Dolan BK, Ulbrich A, Stefely JA, Bohl SL, Werner KM, Jochem A, Westphall MS, Rensvold JW, Taylor RW, Prokisch H, Kim JJ, Coon JJ, and Pagliarini DJ
Molecular Cell, 2016 63(4): 621-32

Cerebellar Ataxia and Coenzyme Q Deficiency Through Loss of Unorthodox Kinase Activity<
Stefely JA*, Licitra F*, Laredj L, Reidenbach AG, Kemmerer AZ, Grangeray A, Jaeg-Ehret T, Minogue CE, Ulbrich A, Hutchins PD, Wilkerson EM, Ruan Z, Aydin D, Hebert AS, Guo X, Freiberger EC, Reutenauer L, Jochem A, Chergova M, Johnson IE, Lohman DC, Rush MJP, Kwiecien NW, Singh PK, Schlagowski AI, Floyd BJ, Forsman U, Sindelar P, Westphall MS, Pierell F, Zoll J, Dal Peraro M, Kannan N, Bingman CA Coon JJ, Isope P, Puccio H†, and Pagliarini DJ†
Molecular Cell, 2016 63(4):608-20

Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis
Stefely JA*, Reidenbach AG*, Ulbrich A, Oruganty K, Floyd BJ, Jochem A, Saunders JM, Johnson IE, Minogue CE, Wrobel RL, Barber GE, Lee D, Li S, Kannan N, Coon JJ, Bingman CA, and Pagliarini DJ,
Molecular Cell, 2015 57(1): 83-94

Last Updated: 3/24/2021 2:18:18 PM

Mitochondria are complex organelles composed of ~1300 proteins, hundreds of which lack clear molecular functions. This image illustrates how our ‘systems biochemistry’ work is helping us to fit these orphan “parts” into the overall mitochondrial “machine.”
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