Explore This Lab


Dr. Dotto received his MD from the University of Turin, Italy, in 1979, and his PhD in Genetics from the Rockefeller University, New York, in 1983. After postdoctoral training with Robert A. Weinberg at the Whitehead Institute/MIT in Cambridge, Mass., in 1987 Dr. Dotto joined Yale University, New Haven, Connecticut, as assistant professor of Pathology. In 1992 he was promoted to the rank of associate professor and soon after moved to Harvard Medical School, as associate professor of Dermatology in the newly established Cutaneous Biology Research Center at Massachusetts General Hospital. In 2000 he was promoted to the rank of Professor at Harvard Medical School and Biologist at Mass General. In 2002 he accepted a position of Professor in the Department of Biochemistry at the University of Lausanne, while retaining his position of Biologist at Massachusetts General Hospital. He has been elected to the European Molecular Biology Organization (2011), the Academia Europaea (2012) and the Leopoldina German National Academy of Sciences (2014). He is the recipient of a number of awards, including the American Skin Association Achievement Award (2012) and an ERC Advanced investigator grant award (2013).

Research Summary

Cancer is a combined result of altered organ and tissue homeostasis, rather than single deregulated groups of cells. Only a minor fraction of pre-malignant lesions progress to malignancy for reasons that are not understood, as many genetic changes found in invasive and metastatic tumors are also found in apparently normal tissues.

The main research focus of the Laboratory Gian Paolo Dotto, MD, PhD at Massachusetts General Hospital is on determinants of pre-malignant to malignant tumor conversion and the field cancerization, a condition of major clinical significance consisting of multifocal and recurrent tumors associated with widespread changes (cancer fields) of surrounding normal tissues. We have started to explore genetic and epigenetic determinants of cancer susceptibility as they relate to gender- and race-related differences. We use skin and Notch signaling as main entry points to understand the complexity of cancer-determining signals.

On the basis of the bad seed / bad soil hypothesis illustrated below, two main topics are being addressed: (i) intrinsic control mechanisms underlying the opposing balance between epithelial cell differentiation and cancer; (ii) role of underlying mesenchymal cells in control of epithelial tumorigenesis.

Field Cancerization: Bad Seed / Bad Soil Hypothesis

Environmental insults, like UV irradiation or smoke, can target both epithelial and stromal compartments of organs such as skin, head/neck, lung, bladder or breast, with ensuing genetic and/or epigenetic changes. Establishment and spreading of “cancer fields” is the likely result of an interplay between epithelial and stromal alterations, with the latter playing an equally important and possibly primary role. The situation leading to multifocal and recurrent neoplastic lesions may be analogous to that of a bad plant difficult to eradicate. This may be due to roots deeply embedded in the terrain or the spreading of bad multiple seeds, growing in the presence of a permissive or favorable soil. An alternative possibility with important conceptual implications is that the main problem is the soil itself. A bad soil could corrupt properties of otherwise perfectly good plants or seeds. According to this view, unless the soil is corrected, various forms of prevention and intervention would be of little or no use.

Lab Members

Principal Investigator: Gian Paolo Dotto

Research team:
Giulia Bottoni
Sandro Goruppi
Andrea Clocchiatti


Selected Publications

Ozdemir BC, Dotto GPRacial Differences in Cancer Susceptibility and Survival: More Than the Color of the Skin? Trends Cancer. 2017 Mar;3(3):181-197. doi: 10.1016/j.trecan.2017.02.002. Epub 2017 Mar 6. Review.

Kim DE, Procopio MG, Ghosh S, Jo SH, Goruppi S, Magliozzi F, Bordignon P, Neel V, Angelino P, Dotto GP. Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation. J Exp Med. 2017 Jul 6. pii: jem.20170724. doi: 10.1084/jem.20170724. [Epub ahead of print]

Dziunycz PJ, Neu J, Lefort K, Djerbi N, Freiberger SN, Iotzova-Weiss G, French LE, Dotto GP, Hofbauer GF. CYFIP1 is directly controlled by NOTCH1 and down-regulated in cutaneous squamous cell carcinoma. PLoS One. 2017 Apr 14;12(4):e0173000. doi: 10.1371/journal.pone.0173000. eCollection 2017.

Ongusaha PP, Kim HG, Boswell SA, Ridley AJ, Der CJ, Dotto GP, Kim YB, Aaronson SA, Lee SW

RhoE Is a Pro-Survival p53 Target Gene that Inhibits ROCK I-Mediated Apoptosis in Response to Genotoxic Stress. Curr Biol. 2016 Aug 22;26(16):2221-2222. doi: 10.1016/j.cub.2016.07.072

Jo SH, Kim DE, Clocchiatti A, Dotto, GP. PDCD4 is a CSL associated protein with a transcription repressive function in cancer associated fibroplast activation. Oncotarget. 2016. Sep. 13;(37):58717-58727. doi: 10.18632/oncotarget.11227.

Lefort K, Ostano P, Mello-Grand M, Calpini V, Scatolini M, Farsetti A, Dotto GP, Chiorino G. Dual tumor suppressing and promoting function of Notch1 signaling in human prostate cancer. Oncotarget. 2016 Jul 26;7(30):48011-48026. doi: 10.18632/oncotarget.10333.

Dotto GP, Rustgi AK. Squamous Cell Cancers: A Unified Perspective on Biology and Genetics. Cancer Cell. 2016 May 9;29(5):622-37. doi: 10.1016/j.ccell.2016.04.004. Review.

Menietti E, Xu X, Ostano P, Joseph JM, Lefort K, Dotto GP. Negative control of CSL gene transcription by stress/DNA damage response and p53. Cell Cycle. 2016 Jul 2;15(13):1767-78. doi: 10.1080/15384101.2016.1186317. Epub 2016 May 10.

Clocchiatti A, Cora E, Zhang Y, Dotto GP. Sexual dimorphism in cancer. Nat Rev Cancer. 2016 May;16(5):330-9. doi: 10.1038/nrc.2016.30. Epub 2016 Apr 15. Review.

Procopio MG, Laszlo C, Dotto GP. CSL-p53: From senescence to CAF activation. Cell Cycle.2016;15(4):485-6. doi: 10.1080/15384101.2015.1130091. Epub 2016 Jan

View my publications at Pub Med