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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.
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.