Organismal growth relies on conserved nutrient sensing pathways, such as mechanistic Target of Rapamycin (mTOR) signaling, that respond to presence or absence of amino acids, growth factors, and nutrients to regulate cellular metabolism. Dysregulation of mTOR signaling can contribute to several human diseases. mTOR signaling has been divided into unique macromolecular protein complexes where mTOR is defined by the binding partners, RAPTOR (mTORC1), RICTOR (mTORC2), and mEAK-7 (mTORC3). In head and neck cancers (HNC), the mTOR signaling pathway has emerged as a critical player, often being dysregulated. Aberrant mTOR signaling can drive tumorigenesis, fostering cancer cell proliferation, survival, and resistance to therapy. The pathway's significance in HNC is underscored by the frequent mutations and amplifications seen in its components. Our lab is focused on understanding the molecular underpinnings of mTOR signaling with the goal of developing therapeutics to enhance cancer immunotherapy and immune checkpoint blockade.

The journey to full-blown head and neck cancers often begins with the formation of pre-malignant oral lesions. These lesions, although not cancerous at their inception, possess a considerable risk of transforming into malignant tumors. We intend to enroll patients in a Natural History Protocol to thoroughly analyze patients with pre-malignant oral lesions. By understanding the molecular and cellular mechanisms underlying the formation and progression of these lesions, we can develop more accurate pre-clinical models. A refined model, in turn, allows for better prediction of disease progression and response to treatments, facilitating the development of more targeted and effective therapeutic strategies.

The insights from mTOR signaling and pre-malignant oral lesion studies hold significant potential for optimizing immune checkpoint therapies. Immune checkpoint blockade, which aims to unleash the body's immune system to recognize and destroy cancer cells, has shown promise in several cancers, including HNC. However, its efficacy can be limited by factors such as tumor immunosuppressive environments. By understanding the role of mTOR signaling in tumorigenesis and the progression of pre-malignant lesions, tailored strategies can be developed to enhance the tumor's visibility to the immune system. This could lead to improved responses to immune checkpoint blockade, offering HNC patients better therapeutic outcomes and potentially longer survival.