Research Labs
Head and Neck Tumor Biology and Immunology
The role of the immune system in the surveillance of host tissues for malignant transformation and cancer development is now well accepted but still poorly understood. Recently, a novel paradigm of solid tumor formation was put forth, proposing that a minor population of cells within a tumor has the exclusive tumor-initiating capacity. These cells have been called cancer stem cells since they possess the ability to self-renew and differentiate into non – cancer stem cells, which comprise the majority population of cells within a tumor but lack the capacity to initiate tumor formation. This cancer stem cell paradigm has been demonstrated in a number of different human malignancies, including head and neck squamous cell carcinoma.
Although cancer stem cells are likely to be the cells that initially undergo transformation by mutations or viral infection, almost nothing is known about the host immune system’s ability to recognize and respond to them. My laboratory is interested in deepening our understanding of these issues. We are particularly interested in the study of a special subset of lymphocytes, called natural killer (NK) cells, which have been described to be critically important in the innate immune response to cells undergoing malignant transformation.
Our work is focused on two primary areas of research:
(1) the immune response to head and neck cancer stem cells
(2) the developmental programs of NK cells.
Our laboratory is located at the Stanford Institute for Stem Cell Biology and Regenerative Medicine and has access to the resources and collaborative potential within the Institute. In addition, our efforts are integrated with and supported by the Stanford Cancer Center and are tightly associated with the clinical endeavors of the Head and Neck Cancer Team link including Head and Neck Surgical Oncology (Drs. Michael Kaplan, Willard Fee, Mike Yao, and Dr. Sunwoo), Medical Oncology (Drs. A. Dimitri Colevas and Harlan Pinto), and Radiation Oncology (Drs. Quynh Le and Billy Loo).
- The immune response to head and neck cancer stem cells.
My laboratory’s overarching goal is to understand how NK cells, in the broader context of the host’s immune system, protect against developing and metastasizing tumor cells, specifically, cancer stem cells, and to understand why this system fails in patients with cancer. Significant heterogeneity of immune potency between individuals with these malignancies has been observed but not explained. We are particularly interested in the questions of how and why the immune system can respond to and control malignant cells in some contexts but not in others. Clarity of the underlying basis for these differences would potentially explain why certain individuals are more susceptible to cancer, lead to better screening strategies, and ultimately provide much needed insight into how the host immune system can be manipulated to control cancer.
- The developmental programs of NK cells.
Another major focus of our laboratory is to decipher the developmental programs of NK cells. In many patients afflicted with cancer, the NK cells from those individuals do not respond to typical NK cell stimuli. A more complete understanding of NK cell development may ultimately reveal potential ways by which malignancies render NK cells dysfunctional. We are particularly interested in understanding the transcriptional regulation of NK cell development and differentiation from stem and progenitor cells. The goal is to further our understanding of the molecular basis underlying NK cell development and maturation, which will in turn provide much needed insight into disorders associated with NK cell defects. In addition, it will potentially provide an understanding of how the development and differentiation of these special lymphocytes can be modulated for therapeutic purposes.
