We conduct basic research to better understand human and animal biology and disease, which informs our translational and clinical research programs.
Sufi Thomas, PhD, leads the Department's Head and Neck Oncology Laboratory. Dr. Thomas specializes in head and neck cancer translational research. She has developed several therapeutic approaches that have been tested in clinical trials. She is currently delineating the mechanism in which cells in the tumor microenvironment facilitate head and neck cancer progression and response to therapy. Several types of normal cells surround the cancer, including blood vessels, immune cells and fibroblasts. Dr. Thomas demonstrated that normal fibroblasts in contact with the tumor facilitate tumor growth and metastasis. Her laboratory is currently identifying the factors secreted by the fibroblasts involved in tumor progression.
Despite improvements in conventional therapies, head and neck cancer continues to be a major challenge with poor 5-year survival rates. Dr. Thomas' main focus has been to understand the biological mechanisms involved in head and neck squamous cell carcinoma (HNSCC) progression in order to develop effective therapeutic interventions. In order to better understand HNSCC biology, it is important to examine the supportive environment that the tumor cells exist in. Several non-tumorigenic cells constitute the cellular stromal environment surrounding the tumor including fibroblasts, immune cells, cells that form blood vessels (endothelial cells and pericytes) and neuronal cells. Fibroblasts are the most abundant stromal type in HNSCC. Emerging evidence demonstrates molecular cross talk between HNSCC and fibroblasts that increase tumor growth, invasion into surrounding tissue and metastasis. Dr. Thomas is in the process of identifying signaling molecules involved in the cross-talk between HNSCC and fibroblasts in order to block tumor growth and metastasis. Molecular biology and biochemical studies using number of preclinical models including cell and tissue culture, cell line xenograft and patient-derived xenograft animal models, and human tissue are used to make these determinations. These studies have tremendous potential in target identification and therapeutic development. However, one of the main impediments to cancer therapy is the paucity of specific inhibitors to emerging molecular targets.
Gene therapy with antisense oligonucleotides can be used to specifically target molecules that are important for tumor growth. Antisense oligonucleotides bind to specific target DNA or RNA sequences interfering with protein synthesis. Dr. Thomas and colleagues successfully developed this approach to target oncogenic epidermal growth factor receptor (EGFR) in HNSCC. Although intra-tumoral administration of EGFR antisense gene therapy has been demonstrated antitumor efficacy in a phase 1 clinical trial, intratumoral injections are not a viable route of administration for tumors that are metastatic or difficult to access. Traditional antisense DNA or RNA based molecules cannot be administered systemically due to rapid degradation by serum enzymes. To circumvent this problem, Dr. Thomas and colleagues developed antisense agents with a pseudo-peptide backbone called guanidinium-peptide nucleic acid (GPNA). This novel class of molecules is resistant to enzymes in serum and has a strong affinity for complementary DNA and RNA sequences. The laboratory is currently developing this approach to target specific gene mutations in HNSCC for therapeutic benefit. This method of systemically delivered antisense oligonucleotides holds immense potential for personalized cancer therapy.
Potential Opportunities for Laboratory Research:
Residents and Fellows are encouraged to participate in basic science or translational research pertaining to the main focus areas of the laboratory. Medical students are invited to apply for a short-term research experience.
To apply, submit the Student Research Interest Form
Contact for more information:
Dr. Kevin Sykes, Director of Clinical Research (firstname.lastname@example.org)