Photo of Nika Danial,  PhD

Nika Danial, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-6436
Fax: (617) 632-5363


Nika_Danial@dfci.harvard.edu

Nika Danial, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Associate Professor, Cell Biology, Harvard Medical School
  • Associate Professor, Cancer Biology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

An evolving body of evidence indicates that the cellular response to physiologic and pathophysiologic stress is highly attuned to the bioenergetic state of the cell, including ATP/ADP ratio and redox status (NADH/NAD). These parameters are predominantly influenced by mitochondrial fuel metabolism. Importantly, the versatility of the mitochondrial metabolome to process alternate energy substrates such as carbohydrates, fatty acids and ketone bodies may feature prominently in the manner in which cells interpret and respond to stress stimuli. The primary focus of the Danial laboratory is to delineate cellular energy and nutrient sensing pathways, including metabolic checkpoints that integrate cellular bioenergetics and cellular responses to stress, including the decision to undergo apoptosis. We employ a multi-disciplinary approach that draws on mouse genetics, mitochondrial physiology, shRNA library screens, chemical biology and proteomics to identify key mechanisms that determine the cell’s choice of energy substrates and thereby modulate cellular stress responses. The ultimate goal of this integrated approach is to uncover potential therapeutic targets in order to manipulate cellular energy metabolism in diseases such as cancer, diabetes and neurodegeneration.

 

Publications

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  • Giménez-Cassina A, Danial NN. Regulation of mitochondrial nutrient and energy metabolism by BCL-2 family proteins. Trends Endocrinol Metab 2015; 26:165-175. PubMed
  • Ljubicic S, Polak K, Fu A, Wiwczar J, Szlyk B, Chang Y, Alvarez-Perez JC, Bird GH, Walensky LD, Garcia-Ocaña A, Danial NN. Phospho-BAD BH3 mimicry protects 硫 cells and restores functional 硫 cell mass in diabetes. Cell Rep 2015; 10:497-504. PubMed
  • Ribeiro SM, Giménez-Cassina A, Danial NN. Measurement of mitochondrial oxygen consumption rates in mouse primary neurons and astrocytes. Methods Mol Biol 2014; 1241:59-69. PubMed
  • Lo JC, Ljubicic S, Leibiger B, Kern M, Leibiger IB, Moede T, Kelly ME, Chatterjee Bhowmick D, Murano I, Cohen P, Banks AS, Khandekar MJ, Dietrich A, Flier JS, Cinti S, Blüher M, Danial NN, Berggren PO, Spiegelman BM. Adipsin is an adipokine that improves 硫 cell function in diabetes. Cell 2014; 158:41-53. PubMed
  • Schoumacher M, Hurov KE, Lehar J, Yan-Neale Y, Mishina Y, Sonkin D, Korn JM, Flemming D, Jones MD, Antonakos B, Cooke VG, Steiger J, Ledell J, Stump MD, Sellers WR, Danial NN, Shao W. Inhibiting Tankyrases sensitizes KRAS mutant cancer cells to MEK inhibitors via FGFR2 feedback signaling. Cancer Res 2014. PubMed
  • Akbay EA, Moslehi J, Christensen CL, Saha S, Tchaicha JH, Ramkissoon SH, Stewart KM, Carretero J, Kikuchi E, Zhang H, Cohoon TJ, Murray S, Liu W, Uno K, Fisch S, Jones K, Gurumurthy S, Gliser C, Choe S, Keenan M, Son J, Stanley I, Losman JA, Padera R, Bronson RT, Asara JM, Abdel-Wahab O, Amrein PC, Fathi AT, Danial NN, Kimmelman AC, Kung AL, Ligon KL, Yen KE, Kaelin WG, Bardeesy N, Wong KK. D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes Dev 2014; 28:479-90. PubMed
  • Giménez-Cassina A, Garcia-Haro L, Choi CS, Osundiji MA, Lane EA, Huang H, Yildirim MA, Szlyk B, Fisher JK, Polak K, Patton E, Wiwczar J, Godes M, Lee DH, Robertson K, Kim S, Kulkarni A, Distefano A, Samuel V, Cline G, Kim YB, Shulman GI, Danial NN. Regulation of hepatic energy metabolism and gluconeogenesis by BAD. Cell Metab 2014; 19:272-84. PubMed
  • Stanley IA, Ribeiro SM, Giménez-Cassina A, Norberg E, Danial NN. Changing appetites: the adaptive advantages of fuel choice. Trends Cell Biol 2014; 24:118-27. PubMed
  • Szlyk B, Braun CR, Ljubicic S, Patton E, Bird GH, Osundiji MA, Matschinsky FM, Walensky LD, Danial NN. A phospho-BAD BH3 helix activates glucokinase by a mechanism distinct from that of allosteric activators. Nat Struct Mol Biol 2014; 21:36-42. PubMed
  • Yan J, Xiang J, Lin Y, Ma J, Zhang J, Zhang H, Sun J, Danial NN, Liu J, Lin A. Inactivation of BAD by IKK inhibits TNF留-induced apoptosis independently of NF-虜B activation. Cell 2013; 152:304-15. PubMed
  • Shah DI, Takahashi-Makise N, Cooney JD, Li L, Schultz IJ, Pierce EL, Narla A, Seguin A, Hattangadi SM, Medlock AE, Langer NB, Dailey TA, Hurst SN, Faccenda D, Wiwczar JM, Heggers SK, Vogin G, Chen W, Chen C, Campagna DR, Brugnara C, Zhou Y, Ebert BL, Danial NN, Fleming MD, Ward DM, Campanella M, Dailey HA, Kaplan J, Paw BH. Mitochondrial Atpif1 regulates haem synthesis in developing erythroblasts. Nature 2012; 491:608-12. PubMed
  • Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB, Polak K, Tondera D, Gounarides J, Yin H, Zhou F, Green MR, Chen L, Monti S, Marto JA, Shipp MA, Danial NN. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell 2012; 22:547-60. PubMed
  • Chae YC, Caino MC, Lisanti S, Ghosh JC, Dohi T, Danial NN, Villanueva J, Ferrero S, Vaira V, Santambrogio L, Bosari S, Languino LR, Herlyn M, Altieri DC. Control of tumor bioenergetics and survival stress signaling by mitochondrial HSP90s. Cancer Cell 2012; 22:331-44. PubMed
  • Fu S, Fan J, Blanco J, Gimenez-Cassina A, Danial NN, Watkins SM, Hotamisligil GS. Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting. PLoS Genet. 2012; 8:e1002902. PubMed
  • Tinoco AD, Kim YG, Tagore DM, Wiwczar J, Lane WS, Danial NN, Saghatelian A. A peptidomics strategy to elucidate the proteolytic pathways that inactivate Peptide hormones. Biochemistry 2011; 50:2213-22. PubMed
  • Gimenez-Cassina A, Danial NN. Noxa: a sweet twist to survival and more. Mol Cell 2010; 40:687-8. PubMed
  • Danial NN, Gimenez-Cassina A, Tondera D. Homeostatic functions of BCL-2 proteins beyond apoptosis. Adv Exp Med Biol 2010; 687:1-32. PubMed
  • Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med 2008; 14:144-53. PubMed
  • Danial NN, Gramm CF, Scorrano L, Zhang CY, Krauss S, Ranger AM, Datta SR, Greenberg ME, Licklider LJ, Lowell BB, Gygi SP, Korsmeyer SJ. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 2003; 424:952-6. PubMed
  • Ranger AM, Zha J, Harada H, Datta SR, Danial NN, Gilmore AP, Kutok JL, Le Beau MM, Greenberg ME, Korsmeyer SJ. Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 2003; 100:9324-9. PubMed
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