“I was born and grew up in China. After I finished my MD degree, I moved to Australia and pursued my PhD degree at the University of Sydney. I obtained my PhD degree in 1999. Then I decided to commit myself to medical research and attended the University of Michigan for my postdoctoral training. During this time, I was well equipped with molecular and biologic techniques to expand my research field. In 2001, I was looking for a lab that focused on CLL research.
I was very interested in Dr. Kipps’ research and was so impressed by his passion for finding the mechanism and cure for CLL that I joined his lab and have been here for the past several years.
I was involved in a project funded by the National Institutes of Health to investigate the difference of two groups of CLL patients. CLL can be segregated into two major subsets based upon the mutational status of the expressed immunoglobulin (Ig) heavy-chain variable region genes (IgVH). Patients with CLL cells that express unmutated IgVH tend to have a relatively aggressive clinical course when compared with patients who have CLL cells that express IgVH with somatic mutations. I made an original and significant contribution of identification of a protein called ZAP-70 in the differentiation between indolent and aggressive forms of CLL. ZAP-70 is essential for signaling through the T-cell antigen receptor. I found that ZAP-70 is uniquely expressed in CLL patients with a poor prognosis. Expression of ZAP-70 is associated with enhanced signal transduction via the BCR complex, which may contribute to the more aggressive clinical course associated with CLL cells that express non-mutated Ig receptors. Subsequently, I discovered that ZAP-70 enhances B-cell receptor signaling by modifying the action of another protein tyrosine kinase called Syk.
These original findings were first presented at the American Society of Hematology (ASH) 2002 annual meeting and later published in the journal Blood (2002, 100:4609-4614). In a continued study, we determined the levels of phosphorylated p72 Syk, BLNK, and PLC and measured the intracellular flux of calcium ([Ca2+]i) following BCR-ligation on CLL cells that did or did not express ZAP-70. Moreover, to test the hypothesis that ZAP-70 is involved in BCR-receptor signaling, we infected CLL cells lacking ZAP-70 with an adenovirus vector encoding this ZAP-70 and then examined for changes in intensity of BCR-signaling. We conclude from our data that expression of ZAP-70 in CLL allows for more effective IgM-signaling in CLL B cells. These original findings were presented at the American Society of Hematology (ASH) 2003 annual meeting and recently published in the journal Blood.
In a study with Dr. Rassenti, we found that ZAP-70 is a better marker for aggressive CLL. These findings were published in New England Journal of Medicine. The recent focus of our work is to investigate why the mechanism ZAP-70 contributes to the progression of CLL. Recently, in a study with Dr Fukuda, we found a new protein expressed in CLL, ROR1. It’s a CLL survival-signaling receptor and can be targeted by the immune response to Ad-ISF35-transduced CLL cells. Now we are investigating the role ROR1 plays in causing CLL. With Dr. Kipps’ insight and thoughts and our hard work, I think we can find the mechanism and a cure for CLL.”