Published in UAB Insight, Spring 2008
Advancing Biomarker and Drug Target Discovery
Early-stage disease detection, the ability to predict and monitor physiological responses to therapy, and identification of novel drug targets are critical points on the path to improved outcomes for patients with cancers and other conditions. With its goal of unraveling the complex actions and interactions of proteins, the budding field of clinical proteomics holds tremendous potential for discovery of drug targets and noninvasive diagnostic and prognostic biomarkers.
By establishing the Urologic and Clinical Proteomics Facility, UAB is investing in infrastructure that can rapidly catalog and quantify proteins and bring the promise of biomarker discovery to patients. The laboratory is unique — the only such facility within a division of urology in the nation — says its director, medicinal chemist James A. Mobley, PhD, who also directs the UAB Comprehensive Cancer Center Proteomics Program.
The facility combines the latest tools in mass spectrometry and small molecule discovery with animal and cellular models and samples from large tumor and biological fluid banks to facilitate in-depth systems biology-based overviews of disease. “The lab’s goal is working with clinicians to generate a truly translational, effective approach to biomarker discovery,” he says. “Biomarkers of prostate cancer aggressiveness, for example, could allow clinicians to determine noninvasively which patients need immediate surgical intervention and which are candidates for watchful waiting.”
Protein activity underlies the pathogenesis of almost all human disease. Proteomics — the study of the proteome — seeks to identify functions, structures, modifications, and interactions of large sets of cellular proteins and uncover the roles these dynamics play in health and disease.
Individual genes produce many proteins, and mapping the human proteome presents scientists with significant technical challenges. Processing and interpreting the data — by some estimates as much as 10 times of that involved in the Human Genome Project — requires advanced, integrated, high-throughput techniques and instrumentation.
“Mass spectometry technology has evolved and now allows sensitive and robust observation and analysis of protein expression profiles,” Mobley says. “These profiles can distinguish normal versus dysregulated processes and lead scientists to biomarkers of various diseases, as well as suggest novel drug targets.”
Proteomics is just starting to fulfill its promise, he says. In this first decade of proteomic discovery scientists have accumulated thousands of terabytes of high-throughput proteomic data but have identified only a limited number of clinically useful biomarkers.
“Biomarker discovery involves sorting through a great deal of heterogeneity among patients and samples,” Mobley says. “One reason identification of useful markers has lagged behind the enormous amount of data acquired is a lack of uniformity in sample acquisition. In UAB’s lab, we are to a great extent overcoming that obstacle by ensuring vigorous consistency.
“By identifying noninvasive clinically relevant markers of disease for general screening and directed diagnosis and prognosis, clinical proteomics offers true translational potential for treatment of disease,” he says.
For more information:
Dr. James Mobley
1.800.UAB.MIST
mist@uabmc.edu