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Research Interests
Infections in immunocompromised host
Natural immunity/Hematopoiesis
Clinincal Interests
Hemoglobinopathies
Tell us about your research interests.
Starting with hematopoeisis- it's more like hemoglobinopathies, which are basically disorders of hemoglobin. Hemoglobin is the molecule inside red blood cells that carries oxygen. Like any protein, you can have a long message to construct that protein, and that causes an abnormal protein or lack of production, and that results in the disease state. So I'm interested in how those diseases present and cause problems, and how to find better ways to treat people. There are several diseases of hemoglobin, but they really come in two different forms: one is that you just don't make enough hemoglobin- the message to make hemoglobin is broken. It's as if you have a tape-recorder with the DNA in it, and you have a tape-recording of how to make that protein, and one set of disorders is that DNA's just not there- so you don't make enough of that protein. Or you make a little bit of it, and it's normal in structure, but you just don't make enough of it.
The other set of disorders is that you make enough of that protein but there's a mistake in the message. That gives you a normal amount, but it's a structure with an abnormal protein. Here in Atlanta the most common disease of this type is sickle-cell anemia. Those are the hemoglobinopathies that I'm interested in working in, and in particular, and in terms of the SURE program, what we're interested in doing is that some of those patients require blood transfusions to treat those conditions, and so patients come once a month for a blood transfusion, and that's a way to treat the condition.
The problem with that is, when you give blood, you also give a lot of iron. Our body doesn't have a system to get rid of iron. Iron is such a scarce thing in the environment that all living organisms have methods of capturing iron and keeping it, and organisms don't have good mechanisms for getting rid of iron because they don't really need those mechanisms; it's such a scarce thing. So when you start giving lots and lots of iron, not-natural amounts like you do with transfusion, that iron accumulates inside the body, and that becomes toxic at a certain level.
So we're trying to understand this iron buildup in children with sickle-cell that are continually receiving transfusions. And we're trying to understand how to measure this iron buildup. There's very little that is understood about how to measure this iron buildup. Basically we're going to look at the common ways of measuring iron buildup that have been used.
One that's been used for a long time is a blood-measure called Feratin. We're going to compare that with a more-recently used technique, which is to measure how much iron there is in the liver. This is also part of clinical management. But these two methods have never really been looked at side-by-side. With the existing data, we're going to look at how these two methods compare.
What sickle-cell disease does is that this abnormal hemoglobin, instead of being in a liquid form, will, at times, polymerize, (link) and develops these spaghetti-like strands inside red cells, and those red-cells clog blood vessels and cause damage by preventing oxygen delivery. Many parts of the body can become damaged that way. One part of the body that can be damaged that way is the spleen, in children. The spleen is an important organ in that it's a filter, basically. It filters red blood cells, but it also filters microorganisms. In children with damaged spleens, they're unable to filter microorganisms.
The way the spleen works, or the way that we think it works, is that, when those bugs go through the spleen, they're trapped there, and the way they're trapped is by two mechanisms. One is that antibodies latch onto the bug, and then the antibodies are recognized by the spleen. There's also another kind of chemical that latches onto those bugs called the complement system. In these children the spleen doesn't work, it gets damaged by sickle-cell disease, and they get a lot more infections by certain types of bacteria that are cleared by the spleen, and one in particular called the pnumoccocus. That's a big problem, because it's the number one cause of death in these children.
What people had found was that a good way to prevent those infections from happening was, first of all, do a newborn screening to find children who are born with sickle-cell disease. For example, in Georgia, it's a universal screening- every child that's born here gets tested for sickle-cell. And then, once you know that a child has sickle-cell, you start those children on penicillin. However, what we're finding is that there is more and more resistance to penicillin. That's more and more of a concern, so what we're interested in now is developing new strategies to prevent those infections. One of them is a new vaccine that's coming out to prevent pneumoccocus. We hope to start testing that in these children.
So what I'm doing is collecting data around the country from eight different sickle-cell treatment centers to find out how frequent the resistance rate is, whether the children that get the resistant organisms have a different infection than those that have non-resistant organisms. And also we're trying to find out the different
What do you teach?
I'm an assistant professor in the department of pediatrics, which means that I teach to medical students, interns, and residents. I teach hematology and oncology, and it's more clinical teaching and seminars, and, later on, I teach the students decision-making. It's a matter of making decisions in a clinical setting. I try to quiz students and try to bring them out more- not in a hostile fashion, but as a part of the learning process. This is what they'll have to do when they're clinicians themselves- make these kinds of decisions.
You have an M.D. rather than a Ph.D. How does that change your perspective on your research?
Nowadays people often do both. I think a Ph.D. gives one a certain rigor in asking scientific questions. But as an M.D., you're obligated to do research during the course of your education. Then, once you are practicing, you're more or less obligated to do it. As a specialist, you realize that within your field there are certain issues that need to be addressed. And since I'm in academia, of course I continued my research.
In terms of the experimentation itself, it's more or less the same, whether you're an M.D. doing experiments or a Ph.D. You have to conduct these experiments in the same way. The difference, perhaps, is that in a clinical setting, you don't have the same degree of control that you have in the lab. In addition, you have to deal with certain ethical issues- these are people you're dealing with, not tissue cultures, and so that limits what you can do. But ultimately, this is where the research is supposed to be applied, in the clinical field.
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