Our research has long been focused on the use of genetically-altered mice to advance our understanding of the biology of the pancreatic beta cell, which plays a central role in the pathophysiology of monogenic and polygenic glycemic disorders including type 1 and type 2 diabetes mellitus.  We have developed novel and efficient methods for rapidly generating mice in which key genes that control cell fate decisions in pancreas development are tagged with different colored fluorescent proteins, conditionally knocked out, or placed under the control of exogenous chemical inducers.  These animals have enabled world-wide advances in multiple facets of both pancreatic and beta cell biology.

Our current research is focused on understanding how genetic and epigenetic factors interact to maintain pancreatic cellular identities.  This is important for two reasons.  First, the loss of beta cell identity, and hence function, may be an important aspect of disease progression in type 2 diabetes mellitus.  To study this we are utilizing mice that lack ATP-sensitive potassium channels and are chronically hyperstimulated independent of the blood glucose concentration.  Second, the development of new cell-based therapies based on reprogramming strategies holds great promise for the treatment of type 1 diabetes mellitus.  Thus, the ability to selectively disrupt acinar cell identity may be critical for the efficient reprogramming of acinar to beta cells by the forced expression of exogenous transcription factors.

In addition to our proven ability to derive state-of-the-art mouse models, we have begun to utilize advanced methodologies, such as RNA-seq and ChIP-seq, to characterize the effects of specific genetic and chemical manipulations on gene expression profile and epigenetic landscape of the cell. The management and analysis of this information has also led us to become interested in the use of both informatics and bioinformatics strategies in order to build models that describe both the gene regulatory networks and epigenetic architectures that determine and maintain specific pancreatic cellular identities.

Publications

Featured publications

  1. Rictor/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis. Tassone B, Saoncella S, Neri F, Ala U, Brusa D, Magnuson MA, Provero P, Oliviero S, Riganti C, Calautti E (2017) Cell Death Differ
    › Primary publication · 28211872 (PubMed)
  2. The mammal-specific Pdx1 Area II enhancer has multiple essential functions in early endocrine-cell specification and postnatal β-cell maturation. Yang YP, Magnuson MA, Stein R, Wright CV (2016) Development
    › Primary publication · 27993987 (PubMed)
  3. Setd5 is essential for mammalian development and the co-transcriptional regulation of histone acetylation. Osipovich AB, Gangula R, Vianna PG, Magnuson MA (2016) Development 143(24): 4595-4607
    › Primary publication · 27864380 (PubMed)
  4. Pancreatic Inflammation Redirects Acinar to β Cell Reprogramming. Clayton HW, Osipovich AB, Stancill JS, Schneider JD, Vianna PG, Shanks CM, Yuan W, Gu G, Manduchi E, Stoeckert CJ, Magnuson MA (2016) Cell Rep 17(8): 2028-2041
    › Primary publication · 27851966 (PubMed) · PMC5131369 (PubMed Central)
  5. Transcriptional Maintenance of Pancreatic Acinar Identity, Differentiation, and Homeostasis by PTF1A. Hoang CQ, Hale MA, Azevedo-Pouly AC, Elsässer HP, Deering TG, Willet SG, Pan FC, Magnuson MA, Wright CV, Swift GH, MacDonald RJ (2016) Mol Cell Biol 36(24): 3033-3047
    › Primary publication · 27697859 (PubMed) · PMC5126291 (PubMed Central)
  6. Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells. Bechard ME, Bankaitis ED, Hipkens SB, Ustione A, Piston DW, Yang YP, Magnuson MA, Wright CV (2016) Genes Dev 30(16): 1852-65
    › Primary publication · 27585590 (PubMed) · PMC5024683 (PubMed Central)
  7. BMP Antagonist Gremlin 2 Limits Inflammation After Myocardial Infarction. Sanders LN, Schoenhard JA, Saleh MA, Mukherjee A, Ryzhov S, McMaster WG, Nolan K, Gumina RJ, Thompson TB, Magnuson MA, Harrison DG, Hatzopoulos AK (2016) Circ Res 119(3): 434-49
    › Primary publication · 27283840 (PubMed) · PMC4961528 (PubMed Central)
  8. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. Satapati S, Kucejova B, Duarte JA, Fletcher JA, Reynolds L, Sunny NE, He T, Nair LA, Livingston KA, Fu X, Merritt ME, Sherry AD, Malloy CR, Shelton JM, Lambert J, Parks EJ, Corbin I, Magnuson MA, Browning JD, Burgess SC (2016) J Clin Invest 126(4): 1605
    › Primary publication · 27035816 (PubMed) · PMC4811133 (PubMed Central)
  9. p16(Ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion. Helman A, Klochendler A, Azazmeh N, Gabai Y, Horwitz E, Anzi S, Swisa A, Condiotti R, Granit RZ, Nevo Y, Fixler Y, Shreibman D, Zamir A, Tornovsky-Babeay S, Dai C, Glaser B, Powers AC, Shapiro AM, Magnuson MA, Dor Y, Ben-Porath I (2016) Nat Med 22(4): 412-20
    › Primary publication · 26950362 (PubMed)
  10. p73 Is Required for Multiciliogenesis and Regulates the Foxj1-Associated Gene Network. Marshall CB, Mays DJ, Beeler JS, Rosenbluth JM, Boyd KL, Santos Guasch GL, Shaver TM, Tang LJ, Liu Q, Shyr Y, Venters BJ, Magnuson MA, Pietenpol JA (2016) Cell Rep 14(10): 2289-300
    › Primary publication · 26947080 (PubMed) · PMC4794398 (PubMed Central)

Community Leaders

  • Mark Magnuson
    Louise B. McGavock Professor of Molecular Physiology and Biophysics
  • Pam Uttz
    Administrative Assistant III

Contact Information

2213 Garland Ave.
9465 MRB IV
Nashville, TN 37232-0494
United States

Pam Uttz
615-322-7006 (p)
615-322-6645 (f)
Email

Keywords & MeSH Terms

MeSH terms are retrieved from PubMed records. Learn more.

Key: MeSH Term Keyword

Adenosine Monophosphate Amino Acid Sequence Blastocyst Bone Morphogenetic Proteins Carbohydrates Chloramphenicol O-Acetyltransferase Chromosomes, Artificial, Bacterial CRISPR DNA Footprinting Embryonic Development endodermal development Fibroblasts Gene Dosage gene networks genetically modified mice HeLa Cells Hot Temperature Human Growth Hormone human pluripotent stem cells Integrases inter-species chimeras iterative WGCNA Molecular Sequence Data pancreas development Perfusion Receptors, Adrenergic, alpha-2 Receptors, Glutamate RNA-Seq scRNA-Seq Substantia Nigra transcription factors