Sarah Franklin

Associate Professor of Internal Medicine and
Adjunct Assistant Professor of Biochemistry

Sarah Franklin

B.S. Brigham Young University

Ph.D. Brigham Young University

Research

References

sarah.franklin@utah.edu

Sarah Franklin's Lab Page

Sarah Franklin's PubMed Literature Search

Molecular Biology Program

Biological Chemistry Program

Chromatin, Chromatin Remodeling Epigenetics, Proteomics, Heart Failure, Heart Disease, Cardiovascular Disease, Mass Spectrometry

 Research

The Franklin lab is investigating epigenetic regulation of gene expression during the development of heart disease. In the nucleus DNA is wrapped around histone proteins, forming nucleosomes. This combination of DNA, histones and other proteins is referred to as chromatin.  Both the DNA and proteins in this complex are susceptible to modifications which can alter the chromatin structure and consequently influence the genes which are transcribed.  Changes in gene transcription can influence cell fate and physiology and have been shown to be altered in disease, including heart disease. Because more people die from heart disease than any other pathology the Franklin lab is interested in identifying the specific factors that regulate gene expression in the heart during disease progression. We are specifically interested in understanding the mechanistic basis for how remodeling of chromatin induces the re-expression of fetal genes in the heart during the development of cardiac hypertrophy and failure. To do this the lab uses a combination of cell and animal models, proteomics, biochemistry and molecular biology to elucidate the function of histone isoforms, post-translational modifications and other chromatin binding proteins on chromatin structure and gene accessibility.

 Selected Publications

  1. Cuellar J, Ludlam W, Tensmeyer N, Aoba T, Dhavale M, Santiago C, Bueno-Carrasco M, Mann M, Plimpton R, Makaju A, Franklin S, Willardson B, Valpuesta J. Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly. (2019) Nature Communications (accepted; in press)

  2. Warren J, Tracy CM, Miller MR, Makaju A, Szulik MW, Yuzyuk TN, Barton DW, Wang L, García J, Sabry AD, Cawley K, Cox J, Yong Hwan Han, Boudina S, Fiehn O, Tucker H, Zaitsev AV, Franklin S. (2018) Histone Methyltransferase Smyd1 Regulates Mitochondrial Energetics in the Heart. PNAS, 115 (33): E7871-E7880. PMID: 30061404.

  3. Tracy C, Warren J, Szulik M, Wang L, Garcia J, Makaju A, Russel K, Miller M, Franklin S. (2017) The Smyd family of methyltransferases: Role in cardiac and skeletal muscle physiology and pathology. Current Opinion in Physiology. 1:140-152.

  4. Miller MR, Franklin S, Foster DB. (2016) Organelle, Protein and Peptide Fractionation in Cardiovascular Proteomics. Chapter In Manual of Cardiovascular Proteomic. Editors: Agnetti, Lindsey and Foster. DOI:10.1007/978-3-319-31828-8.

  5. Franklin S, Kimball T, Rasmussen TL, Rosa-Garrido M, Chen H, Tran T, Miller MR, Gray R, Jiang S, Ren S, Wang Y, Tucker HO, Vondriska TM. (2016)The chromatin binding protein Smyd1 restricts adult mammalian heart growth. AJP-Heart and Circ. Physiol. PMID:27663768. [pdf]

  6. Velinder, M.; Singer, J.; Meznarich, J.; Bareyan, D.; Tracy C. M.; Fulcher, J.; McClellan, D.; Lucente, H.; Franklin, S.; Sharma, S.; Engel, M. E. (2016)Gfi1 functions in transcriptional control and cell fate 1 determination require snag domain methylation to recruit LSD1. Biochem J. 473(19):3355-69. PMID:27480105. [pdf]

  7. Monte E, Rosa-Garrido M, Karbassi E, Chen H, Lopez R, Rau CD, Wang J, Nelson SF, Wu Y, Stefani E, Lusis AJ, Wang Y, Kurdistani SK, Franklin S, Vondriska TM. (2016)Reciprocal Regulation of the Cardiac Epigenome by Chromatin Structural Proteins HMGB and CTCF: Implications for Transcriptional Regulation. J Biol Chem. PMID:27226577. [pdf]

  8. Shimizu H, Schredelseker J, Huang J, Lu K, Naghdi S, Lu F, Franklin S, Fiji HDG, Wang K, Zhu H, Tian C, Lin B, Nakano H, Nakai J, Stieg AZ, Gimzewski JK, Nakano A, Goldhaber JI, Vondriska TM, Hajnóczky G, Kwon O, Chen JN (2015). Mitochondrial Ca2+ uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity. Elife 4. PMID: 25588501. PMID:25588501. [pdf]
  9. Plimpton RL, Cuéllar J, Lai CW, Aoba T, Makaju A, Franklin S, Mathis AD, Prince JT, Carrascosa J, Valpuesta JM, Willardson BM (2015). Structures of the G beta CCT and PhLP1 G beta CCT complexes reveal a molecular mechanism for G protein beta subunit folding and beta gamma dimer assembly.  112(8):2413-8. PMID: 25675501. PMID:25675501. [pdf]
  10. Shibayama J, Yuzyuk T, Cox J , Makaju A, Miller M, Lichter J, Li H, Leavy JD, Franklin S, Zaitsev AV (2015). Metabolic Remodeling in Moderate Synchronous versus Dyssynchronous Pacing-Induced Heart Failure: Integrated Metabolomics and Proteomics Study. PLoS One. 10(3):e0118974. PMID: 25790351. PMID:25790351. [pdf]
  11. Kumar PP, Emechebe U, Smith R, Franklin S, Moore B, Yandell M, Lessnick SL, Moon AM (2014). Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex. Elife 3:e02805. PMID:24876127. [pdf]
  12. Puvula P, Franklin S, Emechebe U, Hu H, Moore B, Lehman C, Yandell M, Moon A (2014). TBX3 regulates splicing in vivo: a novel molecular mechanism for ulnar-mammary syndrome. PLoS Genet. 10(3):e1004247. PMID:24675841. [pdf]
  13. Chen H, Monte E, Vondriska TM, Franklin S. Systems proteomics of healthy and diseased chromatin. Chapter In Heart Proteomics: methods and protocols. Editor: F. Vivanco. Methods Mol. Biol. 2013; 1005: 77-93
  14. Monte E, Chen H, Kolmakova M, Parvatiyar MS, Vondriska TM, Franklin S. Quantitative analysis of chromatin proteomes in disease. J. Vis Exp. 2012 Dec 28; (70): pii: 4294
  15. Chen H, Monte E, Parvatiyar MS, Rosa-Garrido M, Franklin S, Vondriska TM. Structural considerations for chromatin state models with transcription as a functional readout. FEBS Lett. 2012; 586(20): 3548-54
  16. Mitchell-Jordan S, Chen H, Franklin S, Stefani E, Bentolila LA, Vondriska TM. Features of endogenous cardiomyocyte chromatin revealed by super-resolution STED microscopy. J Mol Cell Cardiol. 2012; 53(4): 552-8
  17. Franklin S*, Chen H, Mitchell-Jordan SA, Ren S, Wang Y, Vondriska TM*. Quantitative analysis of the chromatin proteome in disease reveals remodeling principles and identifies high mobility group protein B2 as a regulator of hypertrophic growth. Mol Cell Proteomics. 2012; 11(6): M111.014258 *Denotes co-corresponding authorship
  18. Franklin S*, Vondriska TM*. Genomes, proteomes, and the central dogma. Circulation Cardiovasc Genet. 2011; 4(5): 576. Invited Review
  19. Javaherian AD, Yusifov T, Pantazis A, Franklin S, Gandhi CS, Olcese R. Metal-driven operation of the human large-conductance voltage- and Ca2+-dependent potassium channel (BK) gating ring apparatus. J. Biol. Chem. 2011; 286(23): 20701-9
  20. Franklin S*, Zhang M, Chen H, Paulsson AK, Mitchell-Jordan SA, Li Y, Ping P, Vondriska TM*. Specialized compartments of cardiac nuclei exhibit distinct proteome anatomy. Mol Cell Proteomics. 2011; 10(1): M110.000703 *Denotes co-corresponding authorship
  21. Paulsson AK*, Franklin S*, Mitchell-Jordan SA, Ren S, Wang Y, Vondriska TM. Post-translational regulation of calsarcin-1 during pressure overload induced cardiac hypertrophy. J Mol Cell Cardiol. 2010; 48(6): 1206-14 *Denotes equal contribution
  22. Lomenick B, Hao R, Jonai N, Chin RM, Aghajan M, Warburton S, Wang J, Wu RP, Gomez F, Loo JA, Wohlschlegel JA, Vondriska TM, Pelletier J, Herschman HR, Clardy J, Clarke CF, Huang J. Target identification using drug affinity responsive target stability (DARTS). Proc Natl Acad Sci. 2009; 106(51): 21984-9
  23. Lu G, Sun H, She P, Youn JY, Warburton S, Ping P, Vondriska TM, Cai H, Lynch CJ, Wang Y. Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. J Clin Invest. 2009; 119(6): 1678-87
  24. Mitchell-Jordan SA, Holopainen T, Ren S, Wang S, Warburton S, Zhang MJ, Alitalo K, Wang Y, Vondriska TM. Loss of Bmx non-receptor tyrosine kinase prevents pressure overload-induced cardiac hypertrophy. Circ Res. 2008; 103(12): 1359-62.

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Last Updated: 7/29/19