| Name: | Thomas Pressley, Ph.D. | |
| Job Title: | Associate Professor | |
| Place of work: | Texas Tech Health Sciences Center - Physiology Department | |
TQ team: What is your field of research?
Dr. Pressley: Well, I study ion transport, and the enzyme system that I study is sodium potassium ATPase (Na/K ATPase). It's central to ionic homeostasis in cells. The enzyme catalyzes the transport of sodium potassium ions and is the reason that the interior of cells is depleted in sodium and has an abundance of potassium. This doesn't seem very important, but because of this situation you have a membrane potential, an electrical potential across the plasma membrane, that then forms the basis of action potentials, that allow nerves to communicate, and provides the basis of pacemaking functions in the heart that control the heart beat. It also provides the means by which cells absorb nutrients so that the transfer mechanisms in the GI track depend on this gradient to absorb nutrients. So many, many cellular processes originate from the ion gradients established by NA/K ATPase. That is one of the reasons that I and many other people study it. In addition it is the target for a very important class of drugs, the Digitalis Glycosides, and these are a very popular treatment for heart failure. Digitalis, Digitoxin, and Oubain, all these drugs have an ameliorative effect on the failing heart: increase the strength of the heart beat, increase it's ability to function and their [the drugs] target of action is the NA/K ATPase. One of the things that got me involved is that for many years we thought of the NA/K ATPase of being a single enzyme, and we know now, thanks to molecular biology and some very careful biochemistry and there are very many different variants. One of the central questions that I ask and that many other laboratories ask is: "Why is this necessary?" It seems like a needless complication. The truth is we don't understand why you need so many different kinds of NA/K ATPase. But in the heart clearly there is something going on because the heart expresses different forms. Different parts of the heart express different proportions of the pumps [NA/K ATPase], the proportions of the various types of enzymes change with the heart failure, with the use of drugs. So clearly there is something going on, we just don't have a good handle yet on what that might be. One of the central things we do in my laboratory is try to explore the enzymatic differences between the different forms of the pump and what their structural basis might be. You know, it becomes relevant from the point of view of medicine because of these different forms of the pump react slightly differently to the Digitalis Glycosides and so it becomes a very real question now: what happens to an individual who you are treating Digitalis [Glycosides] long term, what changes in enzyme expression are occurring in the heart, and in response to this? So it's hardly a lewd issue.
TQ team: Wow, I'm trying to grasp all this. In your field of study what progress have you made that you are most proud of?
Dr. Pressley: Um, I would have to say it was the development of antibodies as tools for exploring structure. When I first started doing this about 10 years ago it was still relatively difficult to distinguish between the different forms of the pump [NA/K ATPase]. Most of the reagents that we used were all dependent on the molecular biology, they were all nucleic acid probes or something like that, which doesn't really allow a biochemist to explore the protein very easily: basically we were lacking the tools we thought were necessary to explore the question. So again, about 10 years ago, we started developing what are called site directed antibodies, antibodies that recognize very small pieces of protein, and not surprisingly we picked pieces of the proteins that differed the most among the different forms of the pump and by raising antibodies against those regions we developed a whole panel of antibodies that distinguish between the different forms of the pump. That by itself wasn't a big breakthrough, but then to turn around and use those to explore structure and many different examples of the enzyme was something that hadn't really been tried very much before. So we started calling it 'poor man sequencing.' For example we were able to make predictions about the structure of the pump in fish,which no body had bothered to try and clone out the enzymes for fish, at least at that time they hadn't. But yet we could make some predictions about what the structure of the pump should be like in those animals because of what antibodies bound and what antibodies didn't bound, and so we could make a list of similarities between the mammalian and fish forms and the differences between the mammalian and fish forms, long before we actually saw the actual sequencing. And subsequently a number of labs have cloned out the pump from fish and many of the things we said turned out to be right.
TQ team: You guys started it, it was a revolution!
Dr. Pressley: Hardly (laughs), but these are laboratory tools that have proved to be useful all over the world. I bet I have sent these reagents now to 80 or 90 laboratories all over the world. So when you have a particular question you are asking these are some of the best things to use, of course they are absolutely useless for other questions. We still do that, we still occasionally make antibodies that are corrected against specific sites when we want to ask a particular question.
TQ team: Where did you go to college, and what did you major in?
Dr. Pressley: Um, let's see. Well as an undergraduate I went to John Hopkins University in Baltimore and I actually majored in Earth and Planetary Sciences, which seems a little far off field, but at that time that's where the Paleontology and Ecology professors were located. Hopkins was ahead of it's time in some respects in that the Biology department was very cellular, very molecular, in it's orientation. And at that time in my life that is not what I wanted to do. I thought I wanted to be an Ecologist and do Marine Biology and study interactions between organisms, and so you ended up in what essentially is the old Geology department because that is where all the Paleontologists and Ecologists ended up. It turns out that as I grew older I became more interested in what was happening in the individual animal rather than among different animals and so I gradually drifted more and more towards physiology and biochemistry. By the time I went to graduate school, which was at the Medical University of South Carolina in Charleston, I was doing predominantly Biochemistry and Physiology.
TQ team: Were those two separate majors?
Dr. Pressley: Well, I actually majored in Biochemistry although most of my work was considered physiology. The story behind that is that I was interested in how organisms evolve, and adapt to environmental change. Again that is my ecological background coming into play. The model that I began exploring is salinity acclimation. And in Maryland of course you grew up eating crabs and the blue crab turns out to be a very interesting organism because it can survive in so many different salinities As they moves up and down the estuary they move from nearly fresh water to 100% sea water. Of course that represents a significant challenge for them physiologically. I wanted to try to understand that and very quickly it became apparent that that was a question of how they handled salt transfer. And so I basically became a comparative Physiologist/Biochemist studying the ability of the blue crab to move salt across it's gills, and that's what I did as a graduate student. In the course of pursuing that I became more and more interested in how cells move salts and solutes around and so as a posdoc that's what I started studying. So then from Charleston I went to New York City and did post doctoral training at the College of Physicians and Surgeons at Columbia University and there I learned molecular biology, I learned cell culture, and really learned the tools that I use today. Focusing now at a very molecular level, at the NA/K ATPase, and similar ion transports.
TQ team: Wow, well what do you like best about your job?
Dr. Pressley: The fact that I get to do what I want (smiles). Clearly in an institutional environment the school has expectations for what they would like us to do, I have teaching responsibilities, administrative responsibilities, but the bottom line is that I do the work that I choose to do. Nobody tells me I have to study ion transport. As long as I am successful at what I do they really could care less if I'm studying salt transport, or hormonal balance, or whatever. They judge the success of the program by how much new knowledge I generate and that's is one of the appeals of academics: you don't always have somebody leaning over your shoulder saying "you need to do this, you need to do this." That's also of course the danger. It's that, you know, when you are setting your own goals you have to be careful that you don't become complacent, you have to constantly remind yourself that you shouldn't settle for mediocrity, you have to do the job as well as you can.
TQ team: You gotta rise above.
Dr. Pressley: Yes.
TQ team: You have been very informative, we thank you, but we have a few side questions.
Dr. Pressley: OK.
TQ team: What's your favorite movie?
Dr. Pressley: What's my favorite movie.. Um, that's hard because I enjoy a lot of movies. I try to use movies in the context of the teaching so one that comes immediately to mind is a movie called Body Heat. It starred William Hurt and Catheline Turner and I think was directed by Lawrence Kazan. And it is useful in the teaching because they sweat so much.
TQ team: So you let your classes see movies?
Dr. Pressley: No, but I show a couple of scenes from the movie and you know we joke a lot about it. It [Body Heat] is set in south Florida during a heat wave and there's a couple of scenes between Hurt and Turner where they're just sweatin' bullets.
TQ team: And I guess there's no relation to Elvis Pressley?
Dr. Pressley: Well I'm still waiting for my inheritance check, so I guess not.
