2007 Awardee
Jing Zhang, M.D., Ph.D.

Jing Zhang, M.D., Ph.D., is an Associate Professor of Pathology and Ophthalmology at the University of Washington School of Medicine in Seattle, Washington. He received his initial undergraduate and medical training in Shanghai, China. After graduating from a Ph.D. program in Cell Biology at Duke University in 1995, he finished his medical residency and fellowship in Anatomic Pathology and Neuropathology, respectively, at Vanderbilt University in 2001. While his research focus was centered on brain ischemia in his Ph.D. program, as a neuropathology fellow, Dr. Zhang turned his attention to neurodegenerative disorders, particularly Parkinson’s disease. Since that time, Dr. Zhang has begun applying a novel technology – proteomics – to neurodegenerative research.

Proteomics was developed to study protein expression, structure, and function, typically in a nonbiased and robust fashion. The current intense interest in proteomics is largely driven by two forces: (i) the human genome and the genomes of other organisms have been fully sequenced, making their proteomes accessible; and (ii), proteins, not gene transcripts, are the functional endpoints of gene expression, and it is well established that there is often a poor correlation between the level of mRNA and the level of translated proteins. 

Armed with this state-of-the-art technology, Dr. Zhang and his colleagues have been actively searching for unique proteins involved in Alzheimer’s disease (AD) and Parkinson’s disease (PD), as well as in the aging process. One of the hypotheses being tested is that there are unique protein markers for AD and PD in brain tissue, and that some of these markers have the potential to be detected in human cerebrospinal fluid (CSF) as biomarkers. The research team is comprised of several neuropathologists, i.e. Drs. Ellsworth Alvord, James Leverenz, and Thomas Montine. Another key member of the team is Dr. Elaine Peskind, a prominent AD researcher at the University of Washington who has established one of the largest CSF banks in the country. Finally, Dr. Zhang’s pursuit has been supported by a quite a few investigators from other institutions, including Dr. Joseph Jankovic at the Baylor College of Medicine in Houston, Drs. John Nutt, Kathleen Chung and Joseph Quinn at Oregon Health and Science University, Dr. Marla Gearing at Emory University in Atlanta, Dr. Christine Hulette at Duke University in Durham, Dr. Roger Albin at the University of Michigan, and more recently, Dr. Dennis Dickson at the Mayo Clinic in Jacksonville. Obtaining well characterized human brain and CSF samples from his collaborators is a very important, if not the most important, step towards the success of Dr. Zhang’s proteomics study.

Importance of Published Article
The work presented in the paper "Detection of Biomarkers with a Multiplex Quantitative Proteomic Platform in Cerebrospinal Fluid of Patients with Neurodegenerative Disorders" (JAD 9:293-348, 2006) was performed in Dr. Zhang’s lab with CSF collected at Baylor College of Medicine, Oregon Health and Science University, and the University of Washington in Seattle. This study compared the proteins in CSF from patients with AD, PD and dementia with Lewy bodies (DLB), along with healthy controls. To identify and evaluate these proteins, a quantitative proteomics technique called iTRAQ, a highly sensitive and specific method that relies on isotopic labeling of protein molecules was used, followed by a mass spectrometry analysis. This particular technique is a major improvement on other biomarker detection methods, and the subsequent results of this comparison enabled the researchers to identify and quantify more than 1,500 proteins in CSF samples, as well as to determine unique panels of biomarkers that distinguished AD, PD and DLB not only from controls, but also from each other.  A key component to the research was that three different diseases were analyzed simultaneously along with normal controls, which helped to determine whether a particular protein response was related to a specific disease, and not just a neurodegenerative disease in general. These protein biomarkers, if validated, could be used clinically to assist the diagnosis of these major neurodegenerative disorders, monitoring their progression, as well as gauge therapeutic effects of existing and new pharmacological therapies. As new treatments for AD and PD are developed, the importance of early diagnosis grows. A diagnosis early in the course of the disease increases the likelihood of success from treatments that might slow disease progression, as well as helping patients and their families make plans for future care.