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Research at Mass General
Laboratory of Squamous / Skin Cancer Prevention
Biography: Gian-Paolo Dotto, MD, PhD
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. In 2000 he was promoted to the rank of Professor at Harvard Medical School and Biologist at Massachusetts General Hospital. 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).
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 is on determinants of pre-malignant to malignant tumor conversion and on 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 also 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.
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.
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Cutaneous Biology Research Center
Directions to Charlestown Navy Yard MGH East - Building 149
From Storrow Drive
From the end of Storrow Drive (Leverett Circle) keep to the far right and take a sharp right (do not go up the ramp), and continue beneath the underpass one quarter mile to the light.
Turn left onto Causeway street under the elevated subway tracks. The Fleet Center will be on your left, the North Station T station on your right.
One block past the Garden, turn left on to N. Washington Street, passing over the Charlestown Bridge.
At the first light after the bridge, take a right. Go through three traffic control lights.
At the fourth light, turn right into Navy Yard (Gate 5 - 13th Street). To park, take first left onto Fifth Avenue. Building 149 is one block on the right.
The parking garage entrance is on the right about half way down the block.
Take the Mass Pike (I-90) to I-93 North (Exit 24B)
Take the Storrow Drive Exit (Exit 26)Stay in the left lane once getting on the exit ramp. Follow signs for North Station/Leverett Circle Go through 1 light and take left at the 2nd light (almost immediately after the first)
Get immediately into the right lane
Take a right at the light onto Route 28N
The Museum of Science will be on your left
Take a right at the 3rd light (there is a sign at the corner for Charlestown)
Go over the bridge and get in the right lane (City Square)
Take your 1st right and get into the left lane
Turn left at the 2nd light (immediately before Charlestown Bridge, at City Square) onto Chelsea Street (If you go over bridge, you've gone too far).
Go through three traffic control lights
At the 4th light, turn right into the Navy Yard (Gate 5 - 13th Street).
To park, take first left onto Fifth Avenue. Parking Garage entrance is on the right above half way down the block. Building 149 is one block on the right once you turn into Gate 5. Building 149 is also connected to the parking garage.
Take Exit 28 (Charlestown/Sullivan Square).
At the end of the exit where the read forks stay to the right and proceed past the bus terminal to the rotary at Sullivan Square.
Go halfway around the rotary towards Charlestown (the Schrafts building with a large American flag on top of it will be on your left).
Cross the railroad tracks and take a left at the fire station onto Medford Street.
At the end of Medford street turn left onto Chelsea Street and make an immediate right into the Navy Yard.
The MGH East Research Building (Bldg. 149) will be on the right and is connected to the parking garage by overhead walkways.
Direct the driver to the MGH East, Building 149 in the Charlestown Navy Yard.
The CBRC is on the 3rd Floor of Building 149.By Public Transportation & the MGH/Partners Shuttle
Take the T (Green Line) to North Station
Take the MGH/Partners Shuttle bus to the Charlestown Navy Yard MGH East Research Building (Building 149).
The CBRC is on the 3rd Floor.
The MGH/Partners Shuttle bus leaves MGH on Blossom Street and stops at North Station on Canal Street by the Green Line T stop. The shuttle goes every 15 minutes during working hours. (Less often on the weekends and holidays).
To get to the CBRC, take the first set of elevators to the left of the main entrance by the Security Desk to the third floor. You may need to check in with security on the main level of Building 149.
From the elevator, exit to the East to the CBRC offices, or in the opposite direction for the laboratories.
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