The promise of high-throughput proteomics approaches to reveal new mechanisms of disease has been difficult to realize. There are many reasons for this lack of success, including difficulties in solubilizing and arraying relevant proteins, lack experimental reproducibility, and inadequate data analysis. This lecture chronicles our attempts to discover novel protein biomarkers of alcoholism, and provides a broad overview of the problems inherent in screening proteomic approaches, as well as how we solved them.
The primary focus of our research is to understand the molecular mechanisms underlying the development of opioid tolerance and dependence and the interactions of pain and analgesic signaling. We employ a multidisciplinary approach to understand these problems using cutting-edge techniques. After demonstrating clinical and physiological relevance in animal behavioral studies, we dissect mechanisms underlying opioid tolerance, physical dependence, and pain. We also aim to translate our findings into clinical trials and ultimately, better treatment for cancer patients.
The overall goal of these projects is to develop more effective therapies for treating chronic pain without causing the devastating side effects of tolerance, dependence, and addiction. Trainees gain experience integrating molecular, genetic, neuroanatomic, biochemical, and behavioral techniques to explore important neurobiological questions from many perspectives. Close relations with clinical colleagues in the pain clinic provide opportunities to translate our basic findings into clinical practice and eventually see the direct application of our efforts.