The common theme of Prof.sa Silvia Garavaglia’s research is the analysis of the relationship between enzyme structure and function. Structural biology represents the core of her scientific activity and is integrated with detailed biochemical characterization and enzyme kinetic studies. These approaches are also aimed at developing assays suitable for high-throughput screening procedures and at identifying enzyme inhibitors through in silico methods, particularly structure-based rational drug design.

One of the main active research lines concerns the structural and biochemical characterization of NAD+-dependent enzymes. In particular, aldehyde dehydrogenase 1A3 (ALDH1A3), a retinaldehyde-metabolizing enzyme with detoxifying activity, has recently been found to be overexpressed in cancer stem cells from glioblastoma and neuroblastoma. The objective of this project is the design and synthesis of fluorescent compounds capable of selectively binding ALDH1A3, using crystallographic information to guide ligand optimization. The selected molecules are evaluated for specificity, sensitivity, and their potential application as diagnostic tools for the identification and tracing of cancer stem cells in glioblastoma and other solid tumors.

Another research activity focuses on the bioremediation and detoxification of toxic environmental aldehydes, a class of highly reactive compounds generated by industrial processes, combustion products, air pollution, and environmental degradation pathways. These aldehydes can accumulate in living organisms and ecosystems, causing oxidative stress and cellular damage. The project investigates enzymatic strategies for the removal and biotransformation of toxic aldehydes through the characterization of aldehyde-metabolizing enzymes, combining structural biology, enzymology, and biochemical approaches. Particular attention is devoted to understanding the molecular determinants governing substrate recognition, catalytic efficiency, and enzyme stability, with the aim of developing sustainable and biologically based solutions for the detoxification of environmental contaminants. The research also explores the use of chemically modified and free aldehyde substrates to evaluate enzymatic performance under different environmental and physiological conditions.