PHILADELPHIA – Zhe Lu, M.D., Ph.D., Professor of Physiology at the University of Pennsylvania School of Medicine, was selected to be a Howard Hughes Medical Institute (HHMI) investigator last week. HHMI honors and supports some of the nation's most creative biomedical scientists by giving them the opportunity to tackle their most ambitious and risky research projects. Dr. Lu is one of the 56 biomedical scientists chosen. HHMI has committed more than $600 million to support these newly selected investigators.

Dr. Lu is truly humbled by the award, crediting the honor largely to the members of his lab, and is extremely grateful to the supportive environment created by the colleagues in his department and at other institutions throughout his career. “I would never be able to do the research I do today without their support and especially the guidance of such mentors as Professor Roderick MacKinnon at Harvard Medical School [now a HHMI investigator at Rockefeller University], and Professors Paul DeWeer and Clay Armstrong in the Department of Physiology at Penn.” He is delighted that the support from HHMI will enable his lab to develop therapeutic strategies to combat certain diseases that currently lack effective treatment, and to pursue the answers to some fundamental biological questions.    

“These 56 scientists will bring new and innovative ways of thinking about biology to the HHMI community,” said Thomas R. Cech, president of HHMI. “They are poised to advance scientific knowledge dramatically in the coming years, and we are committed to providing them with the freedom and flexibility to do so.”

Lu works on ion channels, tunnels in a cell’s membrane that allow ions – such as potassium or chloride – to enter or exit. He started formulating his ideas about ion channels when he was a postdoctoral fellow in the lab of Dr. Roderick MacKinnon at Harvard University. For nearly a decade he has been exploring the inner workings of ion channels and how this knowledge sheds new light on the pathology of such diseases as cystic fibrosis and MRSA.

For example, last year his lab discovered that an enzyme produced by lung-infecting bacteria further shuts down the channel protein that is defective in cystic fibrosis (CF) patients. Disruption of the function of this channel causes thick mucus to buildup inside the lungs of CF patients. The effect of the bacterial toxin now helps to explain why the severity of CF symptoms did not match the type of genetic mutation. This finding suggests a new therapeutic target for treating lung disease in some CF patients.

More recently, Lu and colleagues demonstrated that a bacterial toxin, sphingomyelinase C, from the common bacterium Staphylococcus aureus disables the controlmechanism of the ion channel in immune-cell membranes. Shutting down ion channels has long been known to suppress the immune response, and the bacteria may use the toxin to neutralize host defenses against bacteria. Their finding suggests that identifying inhibitors against the toxin may provide a new way to combat S. aureus infections. One strain of S. aureus is the much-talked-about MRSA, or methycillin-resistant S. aureus. Specific inhibitors of the toxin may expand the choice of therapies for treating MRSA and other resistant S. aureus infections.

Lu received his MD from Beijing Medical University and his PhD in physiology from the University of Wisconsin-Madison.

HHMI chose the finalists from among 1,070 applications submitted in a nationwide competition, which was announced in 2007. Researchers with 4 to 10 years of experience as faculty members at more than 200 institutions were eligible to apply. To evaluate the applications, HHMI assembled review panels of distinguished biomedical scientists.

This is the first time that HHMI opened up a general competition to the direct application process. Prior institutional approval was not part of the process, as it had been for previous HHMI investigator competitions. It is an approach HHMI used for the first time in November 2006, for a smaller, more focused competition that led to the appointment of 15 physician scientists. HHMI changed the way it selects investigators to ensure that candidates are drawn from a broader and deeper pool of scientists.


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