Over the past years, my laboratory has focused on gene therapies and cancer immunotherapies. My laboratory has also, to a large extent, focused on elucidating the mechanisms underlying the establishment of immune suppressive tumor microenvironments, a major impediment to the success of immune-based cancer therapies and overcoming cancer cells’ resistance to chemo-radiation therapies. Specifically, we have been examining the mechanisms of immune suppression that are mediated by myeloid derived suppressor cells, macrophages, B cells, and T regulatory cells. In addition, we have been studying the biology of cancer initiating cells, the control of differentiation of myeloid cells and tumor associated macrophages, and modulation of the tumor microenvironment, all of which will influence our ability to control malignant disease.

Our laboratory is working to further define the activation of cancer initiating cells, as well as the immunological changes inside the distinct tumor microenvironment, after administration of radiation therapy, chemotherapy, targeted therapeutics, T cell therapy, and antibody-based novel immune checkpoint therapies. This will help researchers and clinicians integrate conventional therapies with the ideal immunotherapies, thereby achieving the maximal therapeutic efficacy in patients. We are also investigating whether and how targeting therapeutics can overcome the stress-/inflammation-induced immune suppression that subsequently interferes with the success of immunotherapy and chemo/radiation therapy.

One of the primary aims of my lab is to examine how novel immune checkpoint pathways influence tumor growth, receptor/ligand interaction, and the tumor microenvironment. We also aim to develop novel therapeutic agents that effectively target tumors or tumor stromal cells, causing an increase local antigen priming and T cell activation/infiltration for subsequent immunotherapy. This is a key component of achieving long-term tumor remission and lasting immune memory. Using our newly developed immune checkpoints, nanotechnology, and T cell therapy, we can improve tumor targeting and reduce toxicity in patients. Collaborating with colleagues, we have been continually successful in obtaining support from NIH, DOD, and pharmaceutical companies, with the aim of developing novel therapeutic strategies through preclinical and clinical trials.