Sugar Breakdown, Safety Rundown

The very first talk I attended on Sunday morning was by Craig J. Thomas from the NIH Chemical Genomics Center. I wandered in in time to see only the last couple of slides, but I was intrigued enough to ask Craig for more details during lunch. That’s because he and his coworkers are collaborating with Lewis C. Cantley at Harvard Medical School and his company Agios Pharmaceuticals. I blogged about Cantley and Agios a little over a week ago- the company is working toward cancer therapies that selectively target key enzymes involved in metabolic pathways, including the glucose breakdown process known as glycolysis.

From Cantley’s work, we know that it might be possible to tackle tumor cells by targeting a specific form of pyruvate kinase, an enzyme that catalyzes the final step in glycolysis. Thomas’s talk unraveled a bit more of the biochemistry involved. Apparently, the form of pyruvate kinase that is expressed in all tumor cells studied to date, called pyruvate kinase M2, has a slower catalytic cycle compared to the form in normal cells (pyruvate kinase M1). Phosphorylated peptides found in cancer cells slow it down even more.

Thomas, biochemist Doug Auld and their team at NIH are aiming to boost M2’s catalytic turnover to levels normally associated with M1. The idea is that that will bring cancer cells’ metabolism back to normal, so they’ll proliferate more like normal, healthy cells. In preliminary tests in cancer cell lines, at least two families of molecules seem to do the trick, including a set of bis-sulfonamides. The team has submitted two manuscripts on the identification and optimization of the molecules and is preparing a more comprehensive paper dealing with their mechanism and biological activity, Thomas says.

Later that day, I sat in on “Ask Dr. Safety,” a discussion sponsored by the Division of Chemical Health and Safety. Chemical safety consultant Neal Langerman chaired the session, and several other division members were on hand to answer questions as well.

Neal Langerman fields a question (Drahl/C&EN)

Neal Langerman fields a question (Drahl/C&EN)

I was curious whether the topic of pyrophoric reagents would come up, given the extensive coverage of the t-BuLi fire that ultimately claimed the life of Sheri Sangji. By the time I arrived, participants were already deep in discussion about how to classify compounds’ pyrophoricity. Also discussed: what type of syringe is best to use for handling pyrophorics (while each option, glass Luer-Lok; glass, gas-tight Luer-Lok; or plastic had both advantages and disadvantages, the consensus was that extensive training in how to properly handle whatever syringe transfer method is used is more important than the actual syringe) and what types of gloves to wear (protection from fire should be the priority, because dexterity/technique can be learned by practice if gloves lead to more clumsiness than usual). Feel free to chime in in the comments with your thoughts on these areas.

Overwhelmingly, the folks in the audience of 18 had a working involvement with safety, such as a job as an EHS specialist, or as a faculty member on a safety task force at a community college. Part of me had thought that, perhaps, some grad students or postdocs might have shown up with questions of their own, but that didn’t seem to be the case. Location might have had something to do with that- the Plaza hotel is several blocks up the road from the convention center. I’ll admit, I hopped a cab there to avoid the searing heat- I doubt I’d have had much fun walking it. “At the San Francisco meeting, to get to our session, you had to walk through a kitchen,” Langerman says, in a way reminiscent of Rodney Dangerfield.

Author: Carmen Drahl

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