Raffaella Sordella
Associate Professor
Ph.D., University of Turin, 1998
sordella@cshl.edu | (516) 367-5052
Two challenges in cancer biology guide my work: first, how do tumors become addicted to certain gene products, and second, how do tumors develop resistance to anti-cancer drugs. I focus on the epidermal growth factor receptor (EGFR), which is both addictive when mutated and a common source of drug resistance. We are also identifying new targets for the treatment of lung cancer.
Despite their large variety of genetic abnormalities, cancer cells have been found to be extremely sensitive to the reversal of certain mutations. Raffaella Sordella and colleagues study why cells in certain cancers are responsive to the inhibition of one particular gene or gene product. Why, for instance, do non-small-cell lung cancer (NSCLC) cells that have a particular mutation in the epidermal growth factor receptor (EGFR) respond dramatically to its inhibition by the drug Tarceva? This occurs in 15%–20% of patients, the great majority of whom, within 1–3 years, develop resistance. Various mutations have been implicated in about half of resistant patients. Sordella and colleagues have discovered a new resistance mechanism in a subpopulation of NSCLC cells that are intrinsically resistant to Tarceva. These tumor cells were observed to secrete elevated amounts of a growth factor called transforming growth factor-β (TGF-β), which in turn increases secretion of interleukin-6 (IL-6), an immune signaling molecule. Significantly, these effects were independent of the EGFR pathway. The team therefore hypothesizes that inflammation is one of the factors that can render a tumor cell resistant to treatment with Tarceva. In other work, Sordella collaborates with the Krainer lab to study whether alternative splicing has a role in the failure of p53-mediated senescence to halt oncogenesis in certain lung cancers.
New research explains why even targeted therapies eventually fail in lung cancer
March 29, 2017
Cold Spring Harbor, NY — Nearly 50 years into the “war” on cancer, doctors possess weapons that once would have seemed magical in their tumor-killing specificity. The drug Tarceva (erlotinib), for example, can virtually erase all traces of aggressive lung cancer tumors in a subset of patients who bear a particular disease-driving mutation in a...
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
December 9, 2016
Truncated p53 proteins, presumed unimportant, now point to new drug targets for some of ‘the hardest cancers’ Cold Spring Harbor, NY — Discovered in the 1970s, tumor suppressors are among the most important proteins in the body. A master regulator of growth—“the guardian of the genome”—the p53 protein monitors cell growth for errors. We rely...
5th Graders spend a day as young scientists
December 16, 2015
…and it was “the best trip ever.” tiny amoeba crawling across a microscope slide is much more likely to grab kids’ attention than a lecture on single-celled organisms. Any science teacher knows that a hands-on demonstration like setting up a microscope or dissecting an earthworm is the most surefire way to engage kids in learning...
Swim Across America fundraiser supports lung cancer research at CSHL
August 12, 2015
Swim Across America held its annual “Cove to Sound” swim at Morgan’s Park in Glen Cove, NY on August 8, 2015. The event raises important funds to support lung cancer research in Dr. Raffaella Sordella‘s laboratory at CSHL. Nitin Shirole and Paola Pisterzi from Raffaella’s lab participated in the event by swimming and Debjani Pal...
Cancer metabolism and country music with first-year student Jackie Giovanniello
March 9, 2015
First-year Watson School student Jackie Giovanniello loves country music. We’ve learned this not so much from Jackie but from her classmates who either now love country music too, or who refuse to ride in her car because of her strict country-only radio policy. Jackie comes from Brooklyn, not an area considered by many to be...
Experts convene at CSHL to scrutinize, assess low-dose CT screening for lung cancer
October 17, 2014
Cold Spring Harbor, NY — At the first annual Lung Cancer Early Detection and Prevention Workshop held at Cold Spring Harbor Laboratory (CSHL) in late September, nearly two dozen physicians, research scientists and hospital administrators took a close scientific view of rapid advances made in recent years to identify lung cancer at its earliest stages....
Research may explain how the body’s foremost anti-cancer ‘guardian’ protein learned to switch sides
July 29, 2014
The Sordella lab, in collaboration with the Krainer lab, identified a major new isoform of the tumor suppressor p53, called p53Ψ and showed that it induces expression of markers of the epithelial-mesenchymal transition and enhances the motility and invasive capacity of cells.
CSHL lung cancer researcher receives $70,000 from Swim Across America-Nassau Suffolk
March 3, 2014
The Swim Across America (SAA) Nassau Suffolk Committee recently distributed the net proceeds of its 2013 Swims—$500,000—to six Long Island and metro area beneficiaries. Cold Spring Harbor, NY — The Swim Across America (SAA) Nassau Suffolk Committee recently distributed the net proceeds of its 2013 Swims—$500,000—to six Long Island and metro area beneficiaries. The funds...
Long Island foundation presents check for $15,000 to support CSHL lung cancer research
October 1, 2013
The Elisabeth R. Woods Foundation (ERWF) presented a check in September for $15,000 to support lung cancer research of CSHL Associate Professor Raffaella Sordella and graduate student Debjani Pal. The Foundation was established in honor of Elisabeth Woods, wife of long time CSHL Association member and current director, James A. Woods. Elisabeth died in 2000...
Elisabeth R. Woods Foundation marks inaugural year
February 26, 2013
Local foundation makes an impact in their first year. Cold Spring Harbor, NY — In just their first year, the Elisabeth R. Woods Foundation has raised $27,000 to support lung cancer research in the laboratory of Dr. Raffaella Sordella at Cold Spring Harbor Laboratory (CSHL). The Foundation was established in honor of Elisabeth Woods, wife...
Smolen, G. A. and Sordella, R. and Muir, B. and Mohapatra, G. and Barmettler, A. and Archibald, H. and Kim, W. J. and Okimoto, R. A. and Bell, D. W. and Sgroi, D. C. and Christensen, J. G. and Settleman, J. and Haber, D. A. (2006) Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proceedings of the National Academy of Sciences of the United States of America, 103(7) pp. 2316-21.
Kwak, E. L. and Sordella, R. and Bell, D. W. and Godin-Heymann, N. and Okimoto, R. A. and Brannigan, B. W. and Harris, P. L. and Driscoll, D. R. and Fidias, P. and Lynch, T. J. and Rabindran, S. K. and McGinnis, J. P. and Wissner, A. and Sharma, S. V. and Isselbacher, K. J. and Settleman, J. and Haber, D. A. (2005) Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Proceedings of the National Academy of Sciences of the United States of America, 102(21) pp. 7665-70.
Haber, D. A. and Bell, D. W. and Sordella, R. and Kwak, E. L. and Godin-Heymann, N. and Sharma, S. V. and Lynch, T. J. and Settleman, J. (2005) Molecular targeted therapy of lung cancer: EGFR mutations and response to EGFR inhibitors. Cold Spring Harbor Symposia on Quantitative Biology, 70 pp. 419-26.
Sordella, R. and Bell, D. W. and Haber, D. A. and Settleman, J. (2004) Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science, 305(5687) pp. 1163-7.
Lynch, T. J. and Bell, D. W. and Sordella, R. and Gurubhagavatula, S. and Okimoto, R. A. and Brannigan, B. W. and Harris, P. L. and Haserlat, S. M. and Supko, J. G. and Haluska, F. G. and Louis, D. N. and Christiani, D. C. and Settleman, J. and Haber, D. A. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. The New England Journal of Medicine, 350(21) pp. 2129-39.
Additional materials of the author atCSHL Institutional Repository