Sayeed Lab: Biomarkers
Principal Investigator: Aejaz Sayeed, PhD, Cancer Biology
Professor Sayeed’s research interests are centered around studying tumor metabolism and molecular signatures associated with different pathological grades of human cancer with an objective to identify the earliest etiological events and associated bio-markers. Two specific projects are underway in his laboratory:
A. Identification of metabolic alterations in hepatocellular carcinoma. Investigating metformin- and enzalutamide-induced transcriptomic and metabolic reprogramming.
As much of the work in the metabolic field to date has focused on rapidly proliferating tumor models and cells in vitro, it is unclear to what extent these metabolic changes are important in slow growing tumors in which metabolic demands are not as extreme. We propose to develop primary cultures from low-, intermediate- and high-grade human HCC tumors to study the metformin-regulated gene signature and metabolism-related gene profiles using whole-transcriptome profiling analysis. The fact that the incidence of HCC in males is three times more than females suggests the involvement of an androgen axis. We propose to test the use of a known androgen receptor inhibitor, enzalutamide in combination with the anti-diabetic drug metformin. Essentially, this study would evaluate the ability of combination therapy of metformin and enzalutamide on primary culture model systems to reprogram cancer cell metabolism and trigger tumor cell death. We have built a strong collaborative team with Thomas Jefferson University investigators and the application for IRB protocol for acquiring tumor specimens is under process.
In pursuit of noninvasive biomarkers of liver cancer our laboratory is characterizing RNA from microvesicles secreted out in media from HCC cell lines in parallel with intracellular RNA. Encouraged by the detection of mRNA in microvesicles, RNA analysis was extended to blood plasma for detection of circulating mRNA in HCC patients of varying clinical stage/grade. Our goal is to develop a complete panel/signature of circulating transcripts in a tumor stage/grade dependent manner. We are particularly interested to detect and quantify mRNA transcripts with diagnostic and prognostic importance and the corresponding protein products of which are not usually secreted or readily detected in the blood. We propose to develop the HCC circulating mRNA profile and study the correlation with the clinical stage and histological grade of HCC. This study would also determine the extent to which detection of these circulating transcripts correlates with their levels within the circulation and tumor tissue, and ultimately the extent to which the method can be used alone and in combination with other biomarkers to detect the presence of HCC in people.
- Siegel, R. L.; Miller, K. D.; Jemal, A., Cancer Statistics, 2017. CA Cancer J Clin 2017, 67 (1), 7-30.