Gian-Paolo Dotto, MD, PhD

Education, training and positions

Dr. Dotto was educated at the University of Turin, Italy, where he received his MD in 1979. He then earned his PhD in bacteriophage genetics at the Rockefeller University, New York, in 1983. He moved for his postdoctoral training at the Whitehead Institute/MIT in Cambridge Mass. and subsequently joined Yale University, New Haven, Connecticut, as assistant professor of Pathology in 1987. He was promoted to the rank of associate professor in 1992 and soon after moved to Harvard Medical School, in the newly established Cutaneous Biology Research Center. In 2000 he obtained the full professorship at Harvard Medical School and a Biologist position at Massachusetts General Hospital.  In 2002 he accepted a position of Professor in the Department of Biochemistry at the University of Lausanne (UNIL), while retaining his position of Biologist at Massachusetts General Hospital. He has been directing the UNIL PhD program in Cancer and Immunology from 2007 to 2019 and has been responsible for Biochemistry teaching to Medical Students since 2004. Since Aug. 1st 2021 he is honorary professor of the Department of Biochemistry at UNIL. He is founder and director of the International Cancer Prevention Institute, established in Epalinges/Lausanne in 2016.

Scientific contributions

The PI has opened major new perspectives on the complex balance that presides tissue homeostasis and tumorigenesis. His laboratory has been studying the interplay between intracellular and intercellular cell communication pathways that operate in this context, focusing on early steps of skin cancer development as a model. Cancers do not arise solely from a single deregulated cell or group of cells but from more widespread alterations of surrounding tissues. In fact, many genetic changes found in invasive and metastatic tumors are also present in apparently normal tissues and, for reasons that are not yet understood, only a minor fraction of pre-malignant lesions progress to malignancy. In this context, the PI ‘s main research has focused on field cancerization, a process of major clinical significance that consists of multifocal and recurrent tumors associated with widespread changes of surrounding normal tissues, which affects the skin as well as multiple internal organs. On the basis of the bad seed / bad soil hypothesis that he proposed, alterations of both epithelial and stromal cell compartments are involved. His laboratory has pioneered studies on the role that Notch/CSL signaling, a major form of cell-cell communication, plays in both compartments of the skin.

Outreach activities

Dr. Dotto is founder and director of the International Cancer Prevention Institute (IPCI) (www.cancerprev.ch), a new paradigm of teaching / research institute and global forum for educators, policy makers and the general public for development of joint interdisciplinary efforts in primary, secondary and tertiary cancer prevention. He has organized several courses and workshops dedicated to this topic (including a recent EMBO meeting in 2018) and has been a driving force for a new collaborative PhD program on cancer prevention (Marie Curie Innovative Training Network, CANCERPREV) starting November 2019. He has brought to the attention the importance of differences in cancer susceptibility related to sex and ethnic background, two sensitive topics that can be tackled beneficially by rigorous scientific hypotheses and approaches.

More broadly, he is dedicating significant efforts to foster communication between natural sciences and humanities, with general opinion articles and a dedicated website (www.nature-thought-society.com). He has recently published a book entitled “Death and Resurrection: An experiment in progress” in which he tackles the conundrum raised by the historical claims of the Christian faith facing the inescapable tenets of Biology and Medicine.

Representative Publications

1. Missero C, Calautti E, Eckner R, Chin J, Tsai L-H, Livingston DM, Dotto GP. Involvement of the cell cycle inhibitor Cip1/WAF1 and the Ela-associated p300 protein in terminal differentiation. Proc Natl Acad Sci USA 1995;  92:5451-55
2. Di Cunto F, Topley G, Calautti E, Hsiao J, Ong L, Seth PK, Dotto GP. Inhibitory function of  p21Cip1/WAF1 in differentiation of primary mouse keratinocytes independent of cell cycle control.  Science, 1998;   280: 1069-1072
3. Rangarajan, A., C. Talora, M. Nicolas, R. Okuyama, C. Mammucari, H. Oh, J. C. Aster, S. Krishna, D. Metzger, P. Chambon, L. Miele, M. Aguet, F. Radtke and G. P. Dotto.  Notch signaling functions as a direct determinant of the exit of keratinocytes from the cell cycle and entry into differentiation.  The EMBO Journal, 2001;   20:3427-3436
4. Nguyen B-C, Lefort K, Mandinova A, Antonini D, Devgan V, Della Gatta G, Koster MI, Zhang Z, Wang J, Tommasi di Vignano A, Kitajewski J, Chiorino G, Roop DR, Missero C and Dotto GP, Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes & Dev. 2006; 20, 1028-42
5. Wu, X., Nguyen, B.C., Dziunycz, P., Chang, S., Brooks, Y., Lefort, K., Hofbauer, G.F., and Dotto, G.P. (2010). Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 465, 368-372
6. Hu, B, Castillo, E., Harewood, L., Ostano, P., Reymond, A., Dummer, R., Raffoul, W., Hoetzenecker, W., Hofbauer, G.F.L. and Dotto, G.P. (2012)  Multifocal Epithelial Tumors and Field Cancerization from Loss of Mesenchymal CSL Signaling. Cell, 149, 1207–1220
7. Dotto, G.P. Multifocal epithelial tumors and field cancerization: stroma as a primary determinant. J Clin Invest. 2014; 124 :1 446-53. doi: 10.1172/JCI72589
8. Procopio, M.G., Laszlo, C., Al Labban, D., Eun Kim, D., Bordignon, P., Jo, S., Goruppi, S., Menietti, E., Ostano, P., Ala, U., Provero, P., Hoetzenecker, W., Neel, V., Kilarski, W., Swartz, M.A., Brisken, C., Lefort¹, K. and Dotto, G.P. (2015) Combined CSL and p53 downregulation promotes cancer-associated fibroblast activation. Nature Cell Bio. 17, 1193–1204  doi:10.1038/ncb3228
9. Dotto, G.P, and Rustgi, A., Squamous cell cancers: a unified perspective on biology and genetics. Cancer Cell 2016; 29, 622-637
10. Katarkar, A., Bottoni, G., Clocchiatti, A., Goruppi, S., Bordignon, P., Lazzaroni^, F., Gregnanin, I., Ostano, P., Neel, V., and G.P. Dotto (2020) NOTCH1 gene amplification promotes expansion of Cancer Associated Fibroblast populations in human skin. Nature Comm. doi: 10.1038/s41467-020-18919-2
11. Ma, M., Ghosh, S., Tavernari, D., Katarkar, A., Clocchiatti, A., Mazzeo, L., Samarkina, A., Epiney, Yu, Y._R. Ho, P.-C., Levesque, M.P. Özdemir, B.C., Ciriello, G., Dummer, R. and G.P. Dotto (2020) Sustained Androgen Receptor signaling is a determinant of melanoma cell growth potential and tumorigenesis. J. Exp. Med. 218. PMID: 33112375
12. Xu, X., Tassone, B., Ostano, P., Katarkar, A., Proust, T., Joseph, J.M., Riganti, C., Chiorino, G., Kutalik, Z., Lefort, K., and Dotto, G.P. (2021). HSD17B7 gene in self-renewal and oncogenicity of keratinocytes from Black versus White populations. EMBO Mol Med 13, e14133.

Opinion articles (mostly in Italian, full text in English provided by links):

1. The death of God (La morte di Dio), Osservatore Romano, 2017, April 18th daily edition and 20th weekly edition
2. The mystery of the empty tomb (Il mistero della tomba vuota), Osservatore Romano, 2017, May 4th
3. Jesus walks by on the road (Gesu’ passa per strada), Osservatore Romano, 2017, June 15th
4. Charlie and Jesus (Charlie e Gesu’), Osservatore Romano, 2017, July 8th
5. Faust and the little donkey (Faust e l’asinello), Osservatore Romano, 2017, August 26th
6. The day and the night (Il giorno e la notte), Osservatore Romano, 2017, October 8th
7. Generated, not created (Generato non creato), Osservatore Romano, 2017, December 25th daily edition; December 21st weekly edition
8. Enlightment of education (Trasmettere significa portare alla luce), Osservatore Romano, 2018 January 4th^th, daily and weekly editions
9. On the cloning of monkeys (Una notizia che va ridimensionata, la clonazione delle scimmie), Osservatore Romano, 2018, January 28th
10. The many shapes of water (Le forme dell’ acqua), Osservatore Romano, 2018, July 21st
11. Humility and Sanctity of wine (Umiltà e santità del vino), Osservatore Romano, 2018, Nov. 10th
12. Faith and science : are they truly irreconcilable ? (Fede e scienza, due vie davvero inconciliabili ?) Vita e Pensiero, 2018, v.6, p. 112-116
13. Gender and sex—time to bridge the gap, EMBO Molecular Medicine, 2019; DOI:10.15252/emmm.201910668
14. Conjectures, refutations and the search for truths: Science, symbolic truths and the devil. EMBO Reports, 2020; doi: 10.15252/embr.201949924
15. To be or not to be: The second law of thermodynamics and the flow of life and death. EMBO Reports, 2020; doi: 10.15252/embr.202050861

Books

1. Death and Resurrection: An experiment in progress. Gian-Paolo Dotto. 2022, February 24th

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