Date of Award
2023
Document Type
Campus Access Dissertation
Degree Name
Doctor of Philosophy in Chemistry (PhD)
Administrative Home Department
Department of Chemistry
Advisor 1
TARUN K. DAM
Committee Member 1
CHRISTO CHRISTOV
Committee Member 2
SHIYUE FANG
Committee Member 3
RUPALI DATTA
Abstract
Biomarkers are disease specific proteins that are overexpressed under pathological conditions. These proteins save lives because they play key roles in early diagnosis of diseases. Many of these biomarkers are glycosylated proteins (glycoproteins) and their receptors (lectins). Current biomarker detection techniques depend on antibodies and/or tagged reagents. Thus, there is a constant need to develop fast and simple detection techniques that do not require antibodies and labeled reagents. We recently developed such a simple method for (glyco)protein purification/identification and found that this method could also be used for biomarker detection. Our method was able to detect biomarker proteins in blood plasma and in other complex mixtures. One of those detected proteins was human Galectin-3 (Gal-3), a protein that serves as a biomarker for multiple diseases such as cancer, cardiovascular diseases, and diabetes. Gal-3 is a multifunctional protein (lectin), which is overexpressed in a wide variety of cellular and pathological events. However, the molecular basis of its multifunctional property and the reasons behind its occurrence in multiple diseases are poorly understood. Our research has revealed that the binding site of Gal-3 shows considerable plasticity to accommodate a completely unexpected group of ligands, namely proteoglycans and their constituents glycosaminoglycans (GAGs). Our findings explain, at least in part, the multifunctional ability of Gal-3 and provide a reason why this protein is involved in so many pathological events. To understand the plasticity of the binding site of Gal-3, several mutants were generated and characterized. I will present the biomarker detection technique and will discuss the binding site plasticity of Gal-3 as revealed by mutational analysis.
Recommended Citation
Kadav, Priyanka Dipak, "DETECTION AND MUTATIONAL ANALYSIS OF A HUMAN PROTEIN ASSOCIATED WITH CANCER AND CARDIOVASCULAR DISEASES", Campus Access Dissertation, Michigan Technological University, 2023.