Pittet, Mikael, PhD
Samana Cay MGH Research Scholar
For the past >20 years I have performed clinical and/or experimental investigations of immune responses in several inflammatory disorders including cancer, atherosclerosis, myocardial infarction and asthma. In my PhD work at the Ludwig Institute for Cancer Research, Switzerland (with Drs Jean-Charles Cerottini and Pedro Romero) I participated in the identification ex vivo of anti-tumor T cells in human patients with cancer. These studies have shown that tumor-specific T cells frequently accumulate at tumor sites but on account of their anergic state fail to control tumor growth. I then joined the Center for Molecular Imaging Research at MGH as a postdoctoral fellow (directed by Dr Ralph Weissleder), established ties with immunology laboratories at Harvard Medical School (Drs. Harald von Boehmer, Khashayarsha Khazaie and Ulrich von Andrian) and used intravital imaging modalities to assess tumor-specific T cell immune responses directly in vivo. The studies identified key roles for TGF-beta signaling and for T regulatory cells in the inhibition of cytotoxic T cell responses.
My laboratory, established in 2007, performs a research program on the host immune response in vivo. We aim to understand better where, when and how immune cells are produced, traffic, and mediate regulatory or effector functions. For example, our recent work has identified new information on the origins, mobilization and amplification of innate immune cells known as monocytes. We have also started to define some aspects of the functional relevance of these cells in enhancing or suppressing inflammation. Our next goals consist to dissect more intimately the responses mediated by monocytes and other host cells in response to various forms of cancers or other inflammatory diseases. Experimental and clinical evidence indicates that diverse populations of immune cells infiltrate the tumor stroma and enhance cancer progression. We aim not only to understand how tumors are able to co-opt tumor-promoting immune cells––both locally and remotely––but also whether new cancer molecular and cellular targets may prove valuable in the diagnosis and treatment of the disease.
To contribute a more dynamic understanding of immune reactions in the body, we examine the behavior and functions of cells by combining several experimental tools. These include classic molecular and cellular techniques, microsurgical procedures and in vivo imaging modalities. In vitro readouts do not always recapitulate the complexity of in vivo environments, thus we use real-time imaging technologies, which permit to assess the immune system quantitatively and in living subjects. We collaborate with various CSB investigators and with other laboratories in Boston, the U.S., and abroad.