Alan H.B. Wu, Ph.D.
Professor of Laboratory Medicine

Contact Information:
Contact Information: wualan@labmed2.ucsf.edu
Tel: (415) 206-3540
Fax: (415) 206-3045
Box 0134

Protein and nucleic acid biomarkers for therapeutic drugs

A major area of research with the School of Pharmaceutical Sciences and Phamacogenomics will be focused on "personalized therapeutics," i.e., the use of biomarkers to determine proper selection and dosing of drugs to maximize efficacy and minimize adverse drug reactions (ADRs). These biomarkers are usually in the form of proteins or nucleic acids that are found in blood. It is likely that many future drugs will require biomarker testing prior to use on individual patients. Although there is much research effort placed on the discovery of new biomarkers, clinical trials are needed to validate their use on real patients. A reduction in patient morbidity and mortality and/or a reduction in healthcare costs are the drivers for this research.

In the area of protein biomarkers, my research has been focused on validating troponin and B-type natriuretic peptide (BNP) for use in cardiovascular disease. These markers are now routinely used for diagnosis of disease, risk stratification for future cardiovascular events, selection of therapies, and monitoring the success of drug therapies. We are currently engaged in a large multi-center clinical trial to determine how BNP can be used to optimize drug therapies for patients with heart failure. High concentrations of this hormone require the use of higher doses of drugs such as -blockers and angiotensin converting enzyme inhibitors. In another clinical trial, we are testing patients with acute coronary syndromes to determine if they are resistance to the antithrombotic effects of aspirin, using a functional test for platelet aggregation. Those who are salicylate resistant require higher dosing or use of alternative medications such as clopidogrel.

In the area of nucleic acid biomarkers, we have identified and recruited patients who have developed side effects when taking lipid lowering drugs. Compared to subjects who tolerate these statins, we have identified polymorphisms in the cytochrome P450 3A4 gene that are associated with the incidence of myalgias and skeletal injury. As the statins differ in how they are metabolized by the liver, the results of this research might be used to select the proper statin for each patient. Warfarin is a widely used anticoagulant that is metabolized by CYP 2C9. Individuals with the *2 or *3 polymorphism have reduced metabolic capabilities. We are engaged in a prospective clinical trial to determine the proper dosage of warfarin with these genotypes.

As Chief of the Clinical Chemistry and Toxicology Laboratories in the Department of Laboratory Medicine, it is my responsibility to deliver relevant and current clinical laboratory services to patients admitted to the San Francisco General Hospital and the surrounding medical community. As such, we have access to patient specimens and clinical outcomes that are necessary to perform these clinical trials. Results of these and other studies are necessary to determine which of these new pharmacogenomic tests should be incorporated into daily clinical practice.

Recent Publications:
1. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AHB, et al. Rapid measurement of B-type natriruetic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002; 347:161-7.

2. Wu AHB, Broussard LA, Hoffman RS, et al. National Academy of Clinical Biochemistry. Laboratory Medicine Practice Guidelines. Recommendations for the Use of Laboratory Tests to Support the Impaired and Overdosed Patients from the Emergency Department. Clin Chem 2003;49:357-79.