Your degree, “M.D., C.M.”, is not one I’m familiar with. What does the C.M. stand for?
Master of surgery. It’s given by schools in the Commonwealth, I graduated from McGill, which is a Commonwealth school.
In one of your recent papers, you and your colleagues identified a single common receptor for three different bacterial pathogens: Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Why is this significant?
I am a pediatrician, and I do infectious diseases, so microbiology comes into my life from the medical side. The three most important killers of children are those three bugs, so anything that they do together is highly significant, because you can use that information to kill three major pathogens with one intervention. The three of them have figured out this one common way to cause meningitis, even though they’re very different bacteria. Viruses also use this door into the brain, which suggests that it’s sort of an Achilles’ heel: you can get into the brain here and the pathogens have figured that out.
What is that receptor? How can we exploit this knowledge?
It’s the laminin receptor, and if you can block it you can stop most of the major pathogens that cause brain infections. The way we’d propose to do that is to immunize using the pieces of the bacteria that are required to get to that receptor. That should stop meningitis from all three major causes of that infection. It’s taken us 30 years to get here, and now we’re working together with several different companies to go ahead with such a vaccine.
At St. Jude’s Research Hospital, you initiated the Children’s GMP Manufacturing Facility and the Translational Trials Unit, which are devoted to new trials in pediatric diseases. Where do you see the biggest opportunities for improving pediatric health, globally speaking?
The biggest killers are usually infections, so our approach is to develop interventions that we can share worldwide, with vaccines that are going to be appropriate to the third world. Our goal is to make something that’s affordable for everybody and we can actually deploy everywhere. We’re not interested in the profit of just selling it in the U.S. – we want it to work for everybody. We’re working with companies and with non-profits.
Some of your other recent work involves sickle cell disease, a condition that increases the risk of pneumococcal sepsis. How does sickle cell disease relate to pneumococcal infection? What did your lab find about the possible treatments or preventative measures for sickle cell patients?
Children with sickle cell disease have a 600 times higher risk of acquiring a fatal pneumonia infection – so they get it a lot and they die. That’s one of those medical clues that we can learn a lot from.
Sickle cell patients have an activated endothelium in their blood vessels – because the sickle cells keep hitting them. The cells in those linings are expressing activated receptors, and the bacteria recognize those receptors and can invade better because there are more doorknobs to grab hold of and move through. In sickle cell patients, we can learn the details of exactly what part of the bacterium is seeing what part of the blood vessel wall, but we can also see how to calm down the blood vessel wall so that interaction can’t happen. In our study, we used statins as a way of calming down the blood vessels.
That part worked as we expected in mice models, but what was surprising was that there was yet another mechanism that we could use to block infection: the statins also blocked the toxin that the bacteria use. This toxin is one of a family that’s widespread in bacteria and they bind to cholesterol in cell membranes and from pores. Now there’s a possibility that you can expand the use of statins to treat other toxin-producing bacteria. So, looking at sickle cell disease taught us something that’s applicable to a broader range of problems.
Where do you see your field in 10 years?
I hope pneumococcal disease will be eliminated, but I don’t think that will happen.
I hope that worldwide there will be a much better disease prevention capability. This bacterium is naturally competent, so it takes up DNA without much stimulation. This makes it difficult to keep it in a cage, because it’s always out shopping for genes, so any vaccine or antibiotic that you use against it, it just goes out to a new store and finds something that can counteract your strategy. So, in order to stop it from using that circumvention technique we need a vaccine that will knock out all the different 92 types of the bacterium. I hope that 10 years from now we’ll have a vaccine that will stop all of them.
If you had to change careers today and you could do anything, what would you do?
What people don’t know about me is that I’m a competitive ballroom dancer, so I would probably dance if I could afford to.
What’s your favorite dance?
The tango. My son is a junior national champion. He’s 17. Next week is a competition – we probably go to 8-10 a year.
What’s your favorite science book?
Ender’s Game – it’s a science fiction book. I’m a trekkie.