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Related Research Units

Endocrinology Research
Kalaany Laboratory Research

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)

Research Background

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.

Publications

  1. Glutamine analogs for pancreatic cancer therapy. Nat Cancer. 2024 Jan; 5(1):2-4. View Abstract
  2. How nearby nutrients shape tumor growth. Elife. 2023 07 17; 12. View Abstract
  3. Ornithine aminotransferase supports polyamine synthesis in pancreatic cancer. Nature. 2023 04; 616(7956):339-347. View Abstract
  4. Adaptation of pancreatic cancer cells to nutrient deprivation is reversible and requires glutamine synthetase stabilization by mTORC1. Proc Natl Acad Sci U S A. 2021 03 09; 118(10). View Abstract
  5. Author Correction: Tumours with PI3K activation are resistant to dietary restriction. Nature. 2020 May; 581(7807):E2. View Abstract
  6. 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
  7. Critical role for arginase 2 in obesity-associated pancreatic cancer. Nat Commun. 2017 08 14; 8(1):242. View Abstract
  8. Starved epithelial cells uptake extracellular matrix for survival. Nat Commun. 2017 01 10; 8:13989. View Abstract
  9. Autophagy is required for glucose homeostasis and lung tumor maintenance. Cancer Discov. 2014 Aug; 4(8):914-27. View Abstract
  10. 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
  11. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011 Aug 18; 476(7360):346-50. View Abstract
  12. Tumours with PI3K activation are resistant to dietary restriction. Nature. 2009 Apr 09; 458(7239):725-31. View Abstract
  13. 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
  14. LXRS and FXR: the yin and yang of cholesterol and fat metabolism. Annu Rev Physiol. 2006; 68:159-91. View Abstract
  15. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 2005 Apr; 1(4):231-44. View Abstract
  16. ECM-induced gap junctional communication enhances mammary epithelial cell differentiation. J Cell Sci. 2003 Sep 01; 116(Pt 17):3531-41. View Abstract

Contact Nada Kalaany

Phone: 617-919-4896
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