Our laboratory focuses on the engineering of human monoclonal antibodies for their use in discovery research and as drugs for the treatment of human diseases. We are working in two broad disease areas: emerging infectious diseases and cancer. We have constructed and characterized one of the largest human antibody phage display libraries ever made with tens of billions of members. Our laboratory uses all of the modern molecular techniques to isolate and characterize human monoclonal antibodies (mAbs) including phage, yeast and mammalian display, human CD34+ stem cell reconstructed mice, memory B-cell sorting and single B cell cloning, in silico modeling and co-crystallographic studies. We have all of the expertise necessary to move human mAbs into clinical trials.

Our laboratory is pursuing active research programs in human monoclonal antibody immunotherapy. In the field of infectious diseases, we are discovering and targeting highly conserved epitopes on viral glycoproteins that are recalcitrant to neutralization escape. These include influenza A and B hemagglutinin and neuraminidase, Spike protein of human SARS and MERS coronaviruses and E-protein on flaviviruses including West Nile Virus and Denge serotypes 1-4. We are using next generation sequencing to characterize the circulating antibodyome of influenza vaccinated volunteers as well as MERS and Ebola survivors to understand host defense against emerging viral pathogens.

In the field of cancer immunotherapy, we are targeting CXCR4 and CAIX on different solid tumors such as breast cancer and renal cell carcinoma. We are also developing mAbs targeting molecules that are involved in checkpoint pathway control of human T cells such as PD1-L and GITR. Our anti-CCR4 mAbs lead to reversal of regulatory T cell (Treg) suppression and are being developed clinically to restore host anti-tumor immunity and to augment and boost natural and vaccine induced immunity for infectious and cancer vaccines. We are also developing chimeric antigen receptor (CAR) retargeted CD8 T cells (CART cells) for their use in cancer immunotherapy with the goal of bringing this therapy to the clinic for the treatment of solid tumors. We have also spent considerable time developing adult stem cell reconstructed humanized mouse models and several models are available to use in mechanistic and therapeutic studies (http://www.humouse.org) and stem cell medicine studies (http://hsci.harvard.edu/humanized-neonatal-mouse-center-hnmc). In addition, we also founded the National Foundation for Cancer Research Center for Therapeutic Engineering (NFCR-CTAE) to assist cancer investigators with the isolation and characterization of new anti-cancer human monoclonal antibodies (see http://research4.dfci.harvard.edu/nfcr-ctae/) and CHAT to discover human antibody drugs that can lead to differentiation of stem cells down directed lineage pathways (see http://hsci.harvard.edu/center-human-antibody-therapeutics-chat).