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. ROCK-nmMyoII, Notch, and gene-dosage link epithelial morphogenesis with cell fate in the pancreatic endocrine-progenitor niche. Bankaitis ED, Bechard ME, Gu G, Magnuson MA, Wright CVE (2018) Development
    › Primary publication · 30126902 (PubMed)
  2. Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain. Fujiyama T, Miyashita S, Tsuneoka Y, Kanemaru K, Kakizaki M, Kanno S, Ishikawa Y, Yamashita M, Owa T, Nagaoka M, Kawaguchi Y, Yanagawa Y, Magnuson MA, Muratani M, Shibuya A, Nabeshima YI, Yanagisawa M, Funato H, Hoshino M (2018) Cell Rep 24(1): 79-94
    › Primary publication · 29972793 (PubMed)
  3. Synaptotagmin 4 Regulates Pancreatic β Cell Maturation by Modulating the Ca Sensitivity of Insulin Secretion Vesicles. Huang C, Walker EM, Dadi PK, Hu R, Xu Y, Zhang W, Sanavia T, Mun J, Liu J, Nair GG, Tan HYA, Wang S, Magnuson MA, Stoeckert CJ, Hebrok M, Gannon M, Han W, Stein R, Jacobson DA, Gu G (2018) Dev Cell
    › Primary publication · 29656931 (PubMed)
  4. Alpha to Beta Cell Reprogramming: Stepping toward a New Treatment for Diabetes. Osipovich AB, Magnuson MA (2018) Cell Stem Cell 22(1): 12-13
    › Primary publication · 29304337 (PubMed)
  5. Defining a Novel Role for the Pdx1 Transcription Factor in Islet β-Cell Maturation and Proliferation During Weaning. Spaeth JM, Gupte M, Perelis M, Yang YP, Cyphert H, Guo S, Liu JH, Guo M, Bass J, Magnuson MA, Wright C, Stein R (2017) Diabetes 66(11): 2830-2839
    › Primary publication · 28705881 (PubMed) · PMC5652607 (PubMed Central)
  6. Chronic β-Cell Depolarization Impairs β-Cell Identity by Disrupting a Network of Ca-Regulated Genes. Stancill JS, Cartailler JP, Clayton HW, O'Connor JT, Dickerson MT, Dadi PK, Osipovich AB, Jacobson DA, Magnuson MA (2017) Diabetes 66(8): 2175-2187
    › Primary publication · 28550109 (PubMed) · PMC5521870 (PubMed Central)
  7. 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 24(4): 731-746
    › Primary publication · 28211872 (PubMed) · PMC5384034 (PubMed Central)
  8. 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 (2017) Development 144(2): 248-257
    › Primary publication · 27993987 (PubMed) · PMC5394757 (PubMed Central)
  9. 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) · PMC5201031 (PubMed Central)
  10. 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)

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 Cell Polarity Chromosomes, Artificial, Bacterial CRISPR DNA Footprinting Embryonic Development endodermal development Fibroblasts Gene Dosage gene networks genetically modified mice Hot Temperature Human Growth Hormone human pluripotent stem cells Integrases inter-species chimeras iterative WGCNA Molecular Sequence Data pancreas development Perfusion Protein Unfolding Pyrazoles Receptors, Adrenergic, alpha-2 RNA-Seq scRNA-Seq Substantia Nigra transcription factors