Dystrophic Epidermolysis Bullosa (EB): Type VII collagen Gene (COL7A1) Mutations by NGS technology
EB is a heritable skin disease manifesting with sub-lamina densa blistering, erosion, chronic ulcers and leading to extensive tissue fibrosis and squamous cell carcinoma. In collaboration with Dr. J. Uitto (P.I.), we are identifying COL7A1 mutations in a large multi-ethnic cohort using a variety of molecular approaches including SNP polymorphism-based linkage analysis, homozygosity mapping, Sanger sequencing and targeted genome sequencing.
PDX Models for Advanced Stage Uveal Melanoma (UM): Targeted Resequencing in Uveal Melanoma Patients
Prognosis for metastatic uveal melanoma is extremely poor. Controlling the growth of hepatic metastases has been a rational approach to extend survival. Patient-derived tumor xenograft (PDX) mouse models provide potential benefit through a personalized medicine approach. In collaboration with Drs. A. Aplin (P.I.) and T. Sato, we aim to develop new uveal melanoma PDX models of liver metastatic uveal melanoma and test relevant NCI-IND agents with the aim of providing the pre-clinical basis for/against their use in metastatic uveal melanoma. These models are being molecularly characterized using high-throughput technologies at the genomic level and will be utilized to test for response and resistance to different therapeutic strategies.
Short and long RNA profiles in pancreatic and prostate cancer patients
MicroRNAs (miRNAs) are small ~22 nt RNAs that are important regulators of post-transcriptional gene expression, and they have been shown to be involved in many cellular processes. In collaboration with Drs. I Rigoustsos (P.I.), and E. Londin we are profiling miRNAs in a variety of tissue types to characterize the human miRNAome, identify signatures of miRNA expression patterns associated with disease, and elucidate the signaling pathways regulated by miRNAs.
Isolation of circulating tumor cells (CTC)
Blood-born biomarkers such as circulating tumor cells (CTC) and cell-free plasma DNA (cfDNA) have been investigated in the peripheral blood of patients with various carcinomas including breast, ovarian, prostate, colorectal and lung cancer. Assessment of CTCs provide a non-invasive accessible source of tumor material, and the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies. We aim (P. Fortina, P.I.) to evaluate CTC detection using a novel microfluidic technology that uses size- and deformability-based capture systems. This platform allows flexibility in the selection of antibody markers and segregates the CTCs in their own chambers, thus, enabling morphological, immunological and genetic characterization at the single cell level. We are currently investigating the incidence and heterogeneity mutational status within single CTCs isolated from individual prostatic cancer patients combining the FDA-approved CellSearch® system for enumeration of CTCs.