The survival rate for head and neck squamous cell carcinomas has not improved in more than four decades, and new approaches to treat these cancers are needed. These tumors present along the mucosal linings of the head and neck and are notably heterogeneous in regards to their prognosis and response to therapy. Unlike advances in other adult cancers, there are no predictive biomarkers to indicate the best treatment options for head and neck cancer patients.

Basic Research

Structure-guided redesign of an antischistosomal drug New drugs to treat schistosomiasis, a disease caused by the blood flukes Schistosoma mansoni (Sm), Schistosoma haemtobium (Sh) and Schistosoma japonicum (Sj), are urgently needed because only treatment with a monotherapy (Praziquantel - PZQ) is used and effective vaccines are not available. Oxamniquine (OXA) has an excellent safety record and it is extremely effective against Sm, but it is no longer used because unlike PZQ, OXA is ineffective against Sh and Sj.

Candidiasis represents the third leading cause of hospital-acquired bloodstream infections in the U.S. Candida albicans, the most commonly isolated human fungal pathogen, is associated with 50% of infections while several non-albicans Candida species (NACS), including Candida tropicalis and Candida parapsilosis, account for the remainder of cases. Only three major classes of antifungals are currently available for treatment and there is a significant demand for new and more effective therapies. A major virulence property of C.

Basic Research

Candida species are the fourth leading cause of hospital-acquired bloodstream infections in the United States with an attributable mortality rate of 40-50%. Oral candidiasis is the most common fungal infection encountered in the general dental practice and immunocompromised individuals, including AIDS patients, are particularly susceptible. Candida albicans is the most frequently isolated species in oral thrush patients. C. albicans and C. glabrata are increasingly being co-isolated from fungal lesions in the oral cavity.C.

Basic Research

Chemotherapy-induced peripheral neuropathy (CIPN) and the associated pain represent a clinically relevant limit to patient treatment with anti-cancerdrugs. Currently, there is no effective treatment for CIPN. Enhanced excitability of peripheral sensory neurons is thought to contribute to the generation and progression of CIPN. By directly affecting membrane excitability, CIPN-causing chemotherapy drugs may enhance neuronal activity eventuating neuroexcitotoxicity and neuropathy.

In this R01 proposal, we plan to use an integrative genomics (Omics) analysis to test two central hypotheses: 1) TF modules form different transcriptional chromatin hubs and co-regulate dynamical interactomes; and 2) an environmental or cellular stimulus such as hormones triggers different transcription modulators to facilitate dynamical chromatin conformation changes. The ultimate goal is to model and analyze TF modules from one- dimension (1D) to three-dimension (3D) scale and describe the relationship between chromatin organization and TF modules.

Basic Research