Denise Faustman, MD, PhD

Institution: Massachusetts General Hospital
Research: TNF Superfamily Receptors and Clinical trials using BCG in type 1 diabetes, Alzhemier’s and COVID-19
Grants & Publications: Harvard Catalyst
Categories: MGH

As Director of the Immunobiology Laboratory at Massachusetts General Hospital (MGH), my research objective is to introduce new therapeutic concepts to treat autoimmune diseases and, more recently, cancer. I have been working in the fields of autoimmunity and immunology for nearly three decades, with a particular interest in identifying new biological processes that may be related to human disease and most frequently on the TNFR2 signaling pathway. The TNF receptor is center to Treg balance with overuse in cancer and underuse in autoimmunity. In the Immunobiology Lab, I lead teams that work to uncover the basic molecular and immunological mechanisms behind human and murine immune pathogenesis as it relates to TNF and translate these new innovations to the clinic. In various forms of autoimmunity (e.g., type 1 diabetes, Sjögren’s syndrome), we found that restoring tumor necrosis factor (TNF, TNFR2 signaling) can selectively eliminate pathogenic T cells and induce beneficial regulatory T cells (Tregs). Our findings have led to the establishment of global and collaborative clinical trial programs using repeat BCG vaccination, a known potent inducer of host TNF, in diverse autoimmune diseases including an effort to decrease the inflammation of Alzheimer’s. At MGH, this nearly century-old, safe and inexpensive vaccine is also being tested for other off-target effects such as for COVID-19 prevention. BCG vaccinations are also being tested in Italy in Phase III clinical trials in patients with multiple sclerosis. In 2015, we gained FDA approval for our protocol for Phase II testing of BCG vaccination in long-term diabetics and also established two new GMP/FDA approved manufacturing processes for BCG. In total, over 7 advanced trials are ongoing in the Immunobiology Labs. In 2018 we published the Phase I efficacy of repeat BCG vaccines in stably restoring blood sugars to the near normal range in long term diabetic subjects, a feat not feasible with insulin alone with safety. The pathway for tolerance induction in humans with TNF appears to be driven strongly by TNFR2 and now this is a target for both agonistic and antagonistic antibodies for the clinic.