Research in the Wu Lab focuses on how best to effectively mount human immune responses to recognize and eradicate cancer, with dedicated effort on the discovery and targeting of tumor antigens. A longstanding theme of our studies has been how best to launch immunotherapeutic efforts in a personalized fashion, initially through studies in the area of hematopoietic stem cell transplantation (HSCT), together with whole tumor cell vaccination (Burkhardt JCI 2013), and more recently through the implementation of personal neoantigen-targeting cancer vaccines (Ott & Hu Nature 2017; Keskin Nature 2019).

Key to our antigen discovery efforts has been our pioneering of approaches to leverage the recent availability of next-generation massively parallel sequencing technologies to perform comprehensive genomic dissection of malignant cells. Our efforts have led to the discovery of key mutated genes and pathways involved in the pathogenesis of chronic lymphocytic leukemia (CLL) (N Engl J Med, 2011), the development of animal models reflective of human leukemia genetics to interrogate their functional impact, the understanding of the vast clonal heterogeneity of leukemia samples and its impact on clonal evolution (Cell, 2013; Cancer Cell 2014), and the development of resistance to therapy (Nature 2015, Nat Comm 2016; Cancer Cell 2019).

We have further leveraged these sequencing technologies to pioneer computational tools for the comprehensive discovery of potential personal tumor-specific neoantigens (Blood 2014; Nat Biotech 2015; Nat Biotech 2020). Neoantigens are a promising novel class of cancer targets created by the personal mutations found in each patient’s tumor. Because these mutations generate peptides that are distinct from “self”-peptides, the resulting epitopes are expected to escape the immune dampening effects of central tolerance. Ongoing studies focus on developing more effective approaches for building cancer vaccines, with applications across diverse blood and solid tumor malignancies.

Other associated activities

Translational Immunogenomics Laboratory (TIGL), which uses state-of the-art genomic technologies and systems for molecular and cellular analysis of immune response to cancer therapeutics

DFCI CIMAC –CIDC Network, an initiative of the NCI Cancer Moonshot that provides cutting-edge technology and expertise in genomic, proteomic, and functional molecular analysis to enhance clinical trials in cancer immune therapies