Howard Hang: An immunologist's chemist

Credit: © 2008 Landon Nordeman" /> Credit: © 2008 Landon Nordeman As a high school student trying to pick a college, Howard Hang was more interested in where he would be able to catch the best waves than academic programs. A native Californian, Hang looked at many of the University of California schools, finally choosing UC, Santa Cruz, which clearly had the best surf. It wasn't long before his surfboard was

May 1, 2008
Andrea Gawrylewski
<figcaption> Credit: © 2008 Landon Nordeman</figcaption>
Credit: © 2008 Landon Nordeman

As a high school student trying to pick a college, Howard Hang was more interested in where he would be able to catch the best waves than academic programs. A native Californian, Hang looked at many of the University of California schools, finally choosing UC, Santa Cruz, which clearly had the best surf. It wasn't long before his surfboard was gathering dust, and Hang became serious about science, "The 'science bug' didn't catch me until I took organic chemistry, and then things started to actually make sense," recalls Hang.

At Santa Cruz, Hang attended a seminar given by UC Berkeley's Caroline Bertozzi, who spoke on chemical remodeling of mammalian cell surfaces by feeding the cells with unnatural sugars. "For a young chemist, that was awesome," says Hang, recalling his reaction to the seminar. Right away he applied for a summer internship in Bertozzi's lab, and spent the summer between his junior and senior years at Berkeley.

Although Hang looked at other labs for his PhD, he returned to Bertozzi's lab in 1998, where he developed many chemical reporters to study posttranslational modifications, creating profiles of glycoproteins in the cell. Many of the reporters Hang designed during that time were licensed and are now commercially available. In 2003, he showed that a label could be attached chemically to glycoproteins 1 and that a key pathway in glycolysis could tolerate these chemical markers. The approach has been a boon to the study of glycolysis. 2

During this time he also developed his natural mentoring abilities. On the morning of her PhD qualifying exams, Jennifer Prescher, also in Bertozzi's lab, was a nervous wreck about the upcoming grilling and started pacing back and forth in Hang's lab section. "He made me recite 'Who's a superstar? Jenn's a superstar!' over and over. Howard always had a very calming influence on me," says Prescher.

During graduate school, Hang became increasingly fascinated by the interactions between pathogens and host cells. For his postdoc he looked for a lab where he might use the chemical tools he had developed at Berkeley to study biological problems in immunity. In 2004 he joined Hidde Ploegh's lab, where Hang began using chemical tools to study how pathogens perturb cell pathways. "I learned to isolate dendritic cells from a mouse, to prepare a specific population of cells," says Hang. "That's an experience I never thought I would have: working on animals as a chemist." In 2005, Hang attached fatty acids to proteins in vitro to identify those that were involved in the process of infection. Following up with knockout mice, he and collaborators showed that asparagine endopeptidase is essential for the development of CD4 and T cells. 3

"Howard is particularly good at finding and populating that niche of scientific questions that are doable from a chemical perspective but haven't been looked at by biologists," says Ploegh.

In February 2007, Hang started up his own lab in chemical biology and microbial pathogenesis at The Rockefeller University, where he concentrates primarily on tuberculosis and pathogens that cause lung infections. "We want to keep pushing the limits of what we can do with chemistry," he says, "to study how viruses and bacteria perturb host cells."