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Research Overview

A main focus of the Kalaany lab is to investigate the correlation between systemic metabolism and cancer incidence and progression, with the goal of identifying metabolic dependencies that could be targeted therapeutically in cancer patients.

Altered metabolism is a hallmark of cancer. It is however, not only driven by cell-autonomous genetic alterations in oncogenes and tumor suppressor genes, but also by the surrounding tissue microenvironment, as well as the systemic macroenvironment of the host. Evidence for a robust correlation between systemic metabolism and cancer incidence and progression has been accumulating for over a century. For instance, the anti-tumorigenic effects of dietary restriction have been recognized since the early 1900s. Moreover, recent epidemiological studies demonstrate a linear correlation between obesity, type 2 diabetes and mortality from cancers of a wide variety of tissues. Conversely, cancer-associated cachexia, or the organismal energy-wasting syndrome that degrades muscle and fat, can be detrimental to many cancer patients, negatively impacting their quality of life and shortening survival.

Using different models of lung and pancreatic cancer, the Kalaany lab aims at identifying metabolic dependencies in tumors growing under distinct systemic metabolic states, with the goal of targeting them therapeutically in cancer patients, while minimizing toxicity in normal tissues.

In particular, the Kalaany lab aims at understanding:

  • How tumors survive and thrive in a nutrient-limiting microenvironment
  • How tumor growth and metabolism can be affected by the systemic metabolic state of the host (e.g. dietary restriction, obesity, insulin resistance)
  • How the host systemic metabolic state can, itself, get affected by tumor growth and metabolism (e.g. cancer-associated cachexia, or energy-wasting syndrome)

 

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 uncovered a role for oncogenic signaling in modulating the sensitivity of tumors to dietary restriction. She has since joined the faculty of Boston Children's Hospital, Division of Endocrinology. She is also an Associate Member at the Broad Institute of MIT and Harvard, and a member of the Dana-Farber/Harvard Cancer Center.

Researcher Services

Researcher Areas

  • Cancer
  • Metabolism

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PUBLICATIONS

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