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Research Overview

The goal of our laboratory is to identify the mechanisms underlying the association of obesity/type 2 diabetes and cancer.

Evidence for a robust correlation between systemic metabolism and cancer incidence and progression has been accumulating for over a century. Indeed, the anti-tumorigenic effects of dietary restriction that are known to delay cancer incidence and decrease tumor growth in laboratory rodents, have been recognized since the early 1900s. Moreover, the last quarter of the twentieth century has witnessed a worldwide epidemic surge of obesity and its associated metabolic syndrome (e.g. dyslipidemia, hypertension, hyperglycemia, insulin resistance and type 2 diabetes). Recent epidemiological studies demonstrate a linear correlation between the observed increase in obesity as well as type 2 diabetes and mortality from cancers of a wide variety of tissues. This correlation has been estimated to account, in the United States, for 14% and 20% of all deaths from cancer in men and women, respectively.

Our recent work has unveiled a key role for the PTEN/PI3K pathway in determining tumor sensitivity to dietary restriction at early stages of tumor formation. This signaling pathway, known to integrate extracellular hormonal/growth factor stimuli to regulate cell survival, proliferation, and motility, is frequently mutated in a broad array of human cancers and has therefore been extensively studied. However, the role of PTEN/PI3K pathway in modulating the response of tumors to body metabolism is just starting to emerge.

Our laboratory aims at understanding how signaling pathways, such as PI3K/PTEN, influence tumor initiation and maintenance in the context of obesity and its metabolic syndrome and whether such an effect can be exploited therapeutically.

About Nada Kalaany

Nada Kalaany received her PhD from UT Southwestern Medical Center where she studied the role of nuclear hormone receptors in diet-induced obesity. As a postdoctoral fellow, she worked at the Whitehead Institute at MIT where she unveiled a key role for the oncogenic signaling pathway (PI3K/Akt) in modulating the sensitivity of tumors to dietary restriction. She has since joined the faculty of Boston Children's Hospital, Division of Endocrinology and the Center for Basic and Translational Obesity Research.

Key Publications

  • Curry, N.L., Mino-Kenudson, M., Oliver, T.G., Yilmaz, O.H., Yilmaz, V.O., Moon, J.Y., Jacks, T., Sabatini, D.M., and Kalaany, N.Y. Pten-null tumors cohabiting the same lung display differential AKT activation and sensitivity to dietary restriction. Cancer Discov 2013 3: 908-921.
  • Possemato, R., Marks, K.M., Shaul, Y.D., Pacold, M.E., Kim, D., Birsoy, K., Sethumadhavan, S., Woo, H.K., Jang, H.G., Jha, A.K., Chen, W.W., Barrett, F.G., Stransky, N., Tsun, Z.Y., Cowley, G.S., Barretina, J., Kalaany, N.Y., Hsu, P.P., Ottina, K., Chan, A.M., Yuan, B., Garraway, L.A., Root, D.E., Mino-Kenudson, M., Brachtel, E.F., Driggers, E.M., and Sabatini, D.M. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 2011 476: 346-350.
  • Kalaany, N.Y., and Sabatini, D.M. Tumours with PI3K activation are resistant to dietary restriction. Nature 2009 458: 725-731.
  • Kalaany, N.Y., and Mangelsdorf, D.J., "LXRs and FXR: the yin and yang of cholesterol and fat metabolism", Annu Rev Physiol 2006 68: 159-191.
  • Kalaany, N.Y., Gauthier, K.C., Zavacki, AM, Mammen, P.P., Kitazume, T., Peterson, J.A., Horton, J.D., Garry, D.J., Bianco, A.C., and Mangelsdorf, D.J., "LXRs regulate the balance between fat storage and oxidation", Cell Metab 2005 1: 231-244.

Researcher Services

Researcher Areas

  • Mechanisms of Obesity/Type 2 Diabetes and Cancer

Research Departments

Research Divisions

Researcher Labs


Publications powered by Harvard Catalyst Profiles

  1. Xu H, Lee MS, Tsai PY, Adler AS, Curry NL, Challa S, Freinkman E, Hitchcock DS, Copps KD, White MF, Bronson RT, Marcotrigiano M, Wu Y, Clish CB, Kalaany NY. Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis. Proc Natl Acad Sci U S A. 2018 04 17; 115(16):4228-4233. View abstract
  2. Zaytouni T, Tsai PY, Hitchcock DS, DuBois CD, Freinkman E, Lin L, Morales-Oyarvide V, Lenehan PJ, Wolpin BM, Mino-Kenudson M, Torres EM, Stylopoulos N, Clish CB, Kalaany NY. Critical role for arginase 2 in obesity-associated pancreatic cancer. Nat Commun. 2017 08 14; 8(1):242. View abstract
  3. Muranen T, Iwanicki MP, Curry NL, Hwang J, DuBois CD, Coloff JL, Hitchcock DS, Clish CB, Brugge JS, Kalaany NY. Starved epithelial cells uptake extracellular matrix for survival. Nat Commun. 2017 01 10; 8:13989. View abstract
  4. Karsli-Uzunbas G, Guo JY, Price S, Teng X, Laddha SV, Khor S, Kalaany NY, Jacks T, Chan CS, Rabinowitz JD, White E. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov. 2014 Aug; 4(8):914-27. View abstract
  5. Curry NL, Mino-Kenudson M, Oliver TG, Yilmaz OH, Yilmaz VO, Moon JY, Jacks T, Sabatini DM, Kalaany NY. Pten-null tumors cohabiting the same lung display differential AKT activation and sensitivity to dietary restriction. Cancer Discov. 2013 Aug; 3(8):908-21. View abstract
  6. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, Kalaany NY, Hsu PP, Ottina K, Chan AM, Yuan B, Garraway LA, Root DE, Mino-Kenudson M, Brachtel EF, Driggers EM, Sabatini DM. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011 Aug 18; 476(7360):346-50. View abstract
  7. Kalaany NY, Sabatini DM. Tumours with PI3K activation are resistant to dietary restriction. Nature. 2009 Apr 09; 458(7239):725-31. View abstract
  8. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006 Dec; 11(6):859-71. View abstract
  9. Kalaany NY, Mangelsdorf DJ. LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol. 2006; 68:159-91. View abstract
  10. Kalaany NY, Gauthier KC, Zavacki AM, Mammen PP, Kitazume T, Peterson JA, Horton JD, Garry DJ, Bianco AC, Mangelsdorf DJ. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 2005 Apr; 1(4):231-44. View abstract
  11. El-Sabban ME, Sfeir AJ, Daher MH, Kalaany NY, Bassam RA, Talhouk RS. ECM-induced gap junctional communication enhances mammary epithelial cell differentiation. J Cell Sci. 2003 Sep 01; 116(Pt 17):3531-41. View abstract