"Innovation requires an open mind and continued challenging of current paradigms. Discovery requires action based on innovation."
I joined Genentech in 2001 as senior director of immunology and antibody engineering, was named vice president and senior vice president of Research- Immunology in 2003 and 2007, respectively. In 2010, I was appointed senior vice president- Research Biology and oversee our research opportunities.
Genentech is one of the few places in the world where scientists have the ability to study basic biology, make new biological or technological discoveries, identify the pathogenic mechanisms driving human disease, discover new therapies and shepherd these therapies to launch and thereafter impact patients’ lives.
Postdoctoral training and mentorship is an essential part of a scientific career. It provides essential training and scientific experience for the mentee and an opportunity for the mentor to continue learning about new scientific paradigms and train the next generations of scientists.
J Immunotherapy of Cancer 2020; 8:”e001439.
We are studying how autoimmunity-associated genes may be a source of targets to augment cancer immunotherapy. We had previously demonstrated that the protein tyrosine phosphatase PTPN22 is a negative regulator of T-cell antigen receptor (Hasegawa, Science 2004) and interferon-alpha receptor (Holmes, J Exp Med 2015) signaling. Here, we demonstrate that loss of PTPN22 phosphatase enzymatic activity augments both T-cell and interferon-alpha mediated functions leading to spontaneous remission of a number of syngeneic tumor models. In addition, individuals carrying the autoimmune-associated PTPN22(W620R) single-nucleotide polymorphism have lower risk of developing skin cancers and have more favorable responses to anti-PDL1 mAb treatment. These studies demonstrate the importance of host genetics in anti-tumor immunity.
My research interests focus on regulation of immune cell functions. Our immune system is tightly regulated so that it has the ability to efficiently combat infectious pathogens without overexuberant immunity that can cause autoimmune or inflammatory diseases. My recent interests are focused on how modest alterations in lymphocyte signaling results in dysregulated immune cell functions in this tight balance of health and disease.