About

Amy Hauck, PhD, is an assistant professor in the Department of Biochemistry, Molecular Biology and Biophysics at the University of Minnesota Medical School. Her research focuses on how metabolic signals are integrated within the nucleus by a family of transcription factors called nuclear receptors (NRs) and their coregulators to coordinate gene expression patterns. She investigates how derangements in NR signaling and function contribute to metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and Type II Diabetes. Hauck's lab employs an integrated multi-omic approach and novel mouse models to explore the signals and coregulators that determine NR function and genomic occupancy, aiming to better modulate NR activity to combat metabolic disease. Her work emphasizes understanding the mechanisms that dictate and differentiate the activities of NRs in tissue- and disease-specific conditions, with the ultimate goal of developing targeted interventions for metabolic dysfunction.

Research topics

• Biology
• Cell biology
• Biochemistry
• Chemistry
• Endocrinology

Selected publications

• Nuclear receptor corepressors non-canonically drive glucocorticoid receptor-dependent activation of hepatic gluconeogenesis

  Nature Metabolism · 2024-04-15 · 12 citations

  articleOpen access1st author
  PublisherOA PDFDOI

• Short-term cold exposure induces persistent epigenomic memory in brown fat

  Cell Metabolism · 2024-06-17 · 32 citations

  articleOpen access
  PublisherOA PDFDOI

• Balanced control of thermogenesis by nuclear receptor corepressors in brown adipose tissue

  Proceedings of the National Academy of Sciences · 2022-08-08 · 8 citations

  articleOpen access

  Brown adipose tissue (BAT) is a key thermogenic organ whose expression of uncoupling protein 1 (UCP1) and ability to maintain body temperature in response to acute cold exposure require histone deacetylase 3 (HDAC3). HDAC3 exists in tight association with nuclear receptor corepressors (NCoRs) NCoR1 and NCoR2 (also known as silencing mediator of retinoid and thyroid receptors [SMRT]), but the functions of NCoR1/2 in BAT have not been established. Here we report that as expected, genetic loss of NCoR1/2 in BAT (NCoR1/2 BAT-dKO) leads to loss of HDAC3 activity. In addition, HDAC3 is no longer bound at its physiological genomic sites in the absence of NCoR1/2, leading to a shared deregulation of BAT lipid metabolism between NCoR1/2 BAT-dKO and HDAC3 BAT-KO mice. Despite these commonalities, loss of NCoR1/2 in BAT does not phenocopy the cold sensitivity observed in HDAC3 BAT-KO, nor does loss of either corepressor alone. Instead, BAT lacking NCoR1/2 is inflamed, particularly with respect to the interleukin-17 axis that increases thermogenic capacity by enhancing innervation. Integration of BAT RNA sequencing and chromatin immunoprecipitation sequencing data revealed that NCoR1/2 directly regulate Mmp9 , which integrates extracellular matrix remodeling and inflammation. These findings reveal pleiotropic functions of the NCoR/HDAC3 corepressor complex in BAT, such that HDAC3-independent suppression of BAT inflammation counterbalances stimulation of HDAC3 activity in the control of thermogenesis.

  PublisherOA PDFDOI

• Circadian REV-ERBs repress E4bp4 to activate NAMPT-dependent NAD+ biosynthesis and sustain cardiac function

  Nature Cardiovascular Research · 2021 · 66 citations

  • Biology
  • Cell biology
  • Biochemistry
  PublisherOA PDFDOI

• Dichotomous engagement of HDAC3 activity governs inflammatory responses

  Nature · 2020 · 147 citations

  • Cell biology
  • Chemistry
  • Biology
  PublisherOA PDFDOI

• Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

  Antioxidants · 2020 · 31 citations

  1st authorCorresponding
  • Chemistry
  • Biochemistry
  • Cell biology

  ) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

  PublisherOA PDFDOI

• Mitochondrial Oxidative Stress And Adipocyte Protein Carbonylation

  The FASEB Journal · 2019-04-01

  article

  At the molecular level, obesity‐linked type 2 diabetes is characterized by chronic low‐grade inflammation driven by resident macrophages resulting in potentiated adipocyte oxidative stress, mitochondrial dysfunction, lipid oxidation and altered gene expression. Among the many mechanisms linking inflammation to metabolic disease, protein carbonylation has been considered a primary event linking oxidative stress to insulin resistance. Protein carbonylation refers to oxidative posttranslational modification of proteins with reactive lipid aldehydes such as 4‐hydroxy trans 2,3 nonenal (4‐HNE), 4‐hydroxy trans 2,3 hexenal (4‐HHE), or 4‐oxo trans 2,3 nonenal (4‐ONE). Lipid aldehydes are formed at high levels under conditions of increased oxidative stress in visceral, but not subcutaneous, fat tissue and has long been considered a biomarker of oxidative stress in adipocytes, neurons, and muscle cells. Since 4‐HNE and 4‐ONE are derived from lipid peroxidation, C11‐BODIPY 581/591 , a peroxidation‐sensitive sensor, was used to profile which organelle in 3T3‐L1 exhibited the greatest oxidation. Using C11‐BODIPY 581/591 , the mitochondrion exhibited the greatest probe peroxidation and is therefore the likely source of reactive lipid aldehydes in fat cells. Moreover, carbonylation is increased coincident with lipogenesis suggesting that ROS sources in the mitochondrion drive reactive lipid aldehyde formation. Despite the localization of lipid hydroperoxides to the mitochondrion, carbonylated proteins accumulate in the nucleus of visceral, but not subcutaneous, white adipose tissue. Proteomic analysis of carbonylated nuclear proteins reveals that zinc‐finger proteins (ZFP) including the estrogen related receptors a and g are primary targets and result in loss of DNA binding activity. Mapping of carbonylation sites reveals that the DNA/RNA binding domain of ZFPs are primary targets. These results suggest that oxidative stress and lipid peroxidation in the mitochondrion may lead to retrograde signaling of aldehydes to the nucleus culminating in the carbonylation‐dependent inactivation of nuclear zinc‐finger proteins. Support or Funding Information Supported by NIH DK053189 to DAB This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

  PublisherDOI

• Adipose oxidative stress and protein carbonylation

  Journal of Biological Chemistry · 2018-12-19 · 145 citations

  reviewOpen access1st author

  Increased oxidative stress and abundance of reactive oxygen species (ROS) are positively correlated with a variety of pathophysiologies, including cardiovascular disease, type 2 diabetes, Alzheimer's disease, and neuroinflammation. In adipose biology, diabetic obesity is correlated with increased ROS in an age- and depot-specific manner and is mechanistically linked to mitochondrial dysfunction, endoplasmic reticulum (ER) stress, potentiated lipolysis, and insulin resistance. The cellular quality control systems that homeostatically regulate oxidative stress in the lean state are down-regulated in obesity as a consequence of inflammatory cytokine pressure leading to the accumulation of oxidized biomolecules. New findings have linked protein, DNA, and lipid oxidation at the biochemical level, and the structures and potential functions of protein adducts such as carbonylation that accumulate in stressed cells have been characterized. The sum total of such regulation and biochemical changes results in alteration of cellular metabolism and function in the obese state relative to the lean state and underlies metabolic disease progression. In this review, we discuss the molecular mechanisms and events underlying these processes and their implications for human health and disease.

  PublisherOA PDFDOI

• Obesity-induced protein carbonylation in murine adipose tissue regulates the DNA-binding domain of nuclear zinc finger proteins

  Journal of Biological Chemistry · 2018-07-16 · 24 citations

  articleOpen access1st author

  carbonylation decreased the DNA-binding capacity of ERR-γ and correlated with the obesity-linked down-regulation of many key genes promoting mitochondrial bioenergetics. Taken together, these findings reveal a novel mechanistic connection between oxidative stress and metabolic dysfunction arising from carbonylation of nuclear zinc finger proteins, such as the transcriptional regulator ERR-γ.

  PublisherOA PDFDOI

• Adipose Carbonylation and Mitochondrial Dysfunction

  2017-05-17 · 1 citations

  other1st authorCorresponding

  This chapter describes oxidative stress in adipose tissue, its linkage to protein carbonylation, and the current methods used to detect and analyze carbonylated proteins as well as provides a comprehensive evaluation of known proteins and pathways that are targets of these modifications in adipose biology. Although the term oxidative stress encompasses many forms of reactive oxidants, the production and signaling mechanisms of reactive oxygen species (ROS) are the best characterized and are the focus of the chapter. The chapter briefly discusses techniques that have been used successfully to assess carbonylation in adipose tissue or cultured adipocytes. It focuses on the major findings in adipose tissue, though it is prudent to note that many of these findings are relevant to other cell types and diseased states as well. Many of the proteomic studies in adipose and other tissues have focused on mitochondrial targets of 4-hydroxy trans 2,3 nonenal modification.

  PublisherDOI

Frequent coauthors

• David Bernlohr

  University of Minnesota

  7 shared

• Matthew J. Emmett

  Harvard University

  6 shared

• Mitchell A. Lazar

  University of Pennsylvania

  5 shared

• Maria Chondronikola

  University of Cambridge

  4 shared

• Shin‐ichi Inoue

  University of Pennsylvania

  3 shared

• Hee‐Woong Lim

  University of Cincinnati

  3 shared

• Tong Zhou

  Wenzhou Medical University

  3 shared

• Hannah J. Richter

  University of Pennsylvania

  2 shared

Education

• B.A.

  University of San Diego

  2010

• Ph.D., Biochemistry (BMBB)

  University of Minnesota

  2017

• Other

  University of Pennsylvania, Institute for Diabetes, Obesity, and Metabolism