Otolaryngology and Cancer Biology
Bachelors: Bombay University, India
Masters: Mumbai University, India
PhD: Mumbai University, India
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Office Line (913) 588-6664
Lab Phone (913) 945-6579
Understanding the biological mechanisms involved in head and neck squamous cell carcinoma (HNSCC) progression and 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 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. The finding from these studies has tremendous potential in target identification and therapeutic development. Fibroblasts not only facilitate tumor growth but are also contribute to radiation induced fibrosis (RIF). RIF is a progressive side-effect of radiation that has a significant impact on the quality-of-life. Most HNSCC patients treated with radiotherapy develop RIF. Currently there are no effective therapeutic interventions to mitigate this condition. Dr. Thomas' team is developing preclinical models for RIF with a goal of finding new therapeutic targets for intervention.
Gene therapy with antisense oligonucleotides can be used to specifically target molecules that are important for disease progression. Gene mutations and dysregulation of growth factor receptors results in a promotion of tumor growth and contributes to treatment resistance and failure. Currently available antisense DNA or RNA based gene targeted approaches cannot be administered systemically due to rapid degradation by serum enzymes. To circumvent this problem, Dr. Thomas' group in collaboration with Carnegie Melon University has developed an approach to specifically target expression of aberrant proteins up on systemic delivery. This new class of antisense agents with a pseudo-peptide backbone called guanidinium-peptide nucleic acid (GPNA) is resistant to enzymes in serum and has a strong affinity for complementary DNA and RNA sequences. As proof-of-concept, we designed a GPNA antisense oligomer targeting the epidermal growth factor receptor (EGFRAS GPNA). EGFRAS GPNA treatment results in tumor growth inhibition on systemic delivery in animal models. The approach is being developed to target specific mutations and non-druggable targets in cancer. This method of systemically delivered antisense oligonucleotides holds immense potential for personalized cancer therapy.
Vikalp Vishwakarma, PhD
Dhruv Kumar, PhD
Sufi Thomas, Ph.D.
3020A Wahl Hall East, Mail Stop 3010
3901 Rainbow Boulevard
Kansas City, KS 66160
(913) 588-6664 Lab Phone (913) 945-6579