The Dahl lab is focused on the following major endeavors: 1. Using chemical tools to dissect disease relevant biological pathways or mechanisms to discover new drug targets. 2. Validation of novel therapeutic targets using pharmacological modulators in both a traditional drug discovery sense and in a systems-oriented approach exploring complex molecular states typified by disease. 3. Optimizing newly discovered small molecule modulators in the areas of neuroscience and cancer for validation in animal models of disease. In addition, our lab collaborates with other faculty members on various drug discovery-oriented projects, utilizing synthetic chemistry to develop structure-activity-relationships (SAR) to enable preclinical optimization of candidate molecules.
Synthetic Chemistry. Our lab relies heavily on synthetic organic chemistry to generate small molecules to interrogate biological pathways and mechanisms of interest. The lab features state-of-the-art technology for the synthesis, purification, and characterization of molecules. We have automated instrumentation and facilities comparable to those typically found in major pharmaceutical companies. We are interested in both traditional, multi-step syntheses of complex molecules and parallel synthesis of focused chemical libraries to expedite SAR. Within our discovery workflow, we routinely employ in vitro ADMET profiling assays to optimize drug efficacy and disposition in a parallel manner. The lab has expertise in all phases of modern drug discovery and development including structure-based drug design, hit-to-lead and lead optimization, and preclinical optimization of compounds for further drug development.
Neurodegeneration and Cancer. Two areas of interest in our lab are neurodegeneration and cancer. These aging-associated diseases are seemingly opposite -- one is marked by the massive cell death of neurons leading to loss of cognition, and the other is characterized by uncontrolled cell proliferation. However, it has been established that many of the signaling pathways that control cellular fate are common amongst these two seemingly antipodean diseases. We are using small molecules to interrogate multiple cellular signaling pathways to discover putative therapeutic targets for both cancer and neurodegenerative diseases (Alzheimer’s, Parkinson’s). As such, we are focusing on the positive and negative modulation of both cell proliferation and cell death pathways to apply to these diseases.