Articles, Blog

NHLBI Orloff Award 2018: Robert S. Balaban


(light music) I think to understand disease and to understand the human condition, we need to understand how things work. Here on the Bethesda campus of NHLBI, we are working in basic biology, looking at protein structures,
we’re doing cell biology, understanding how cells
work, and then finally, working on the human condition, that is clinical studies,
population studies, and then applying that
information both ways. Taking the clinical data to
drive the basic sciences, taking the basic sciences
where we get opportunities to impact what the clinicians
are doing around the world. My name is Bob Balaban, I’m the Scientific Director for NHLBI, and the Laboratory Chief for the Laboratory of Cardiac Energetics. If there’s one hallmark
of our intramural program, it’s an area of imaging, that is trying to visualize proteins, visualize what cells do,
visualize what happens inside your body and use that information to better understand disease, but then to come up with better therapies. One of the things I’ve been
working on for a long time is trying to get a better understanding of how the body deals with
water, we’re 70% water. I’ve had a great opportunity
for many years to be studying this phenomenon using
magnetic resonance imaging, which is basically an
imaging method of water. One of the frustrating
things is that the resolution of the MRI is rather poor,
we can’t see inside cells, we can only see gross structures. So we developed and worked on
optimizing a technique called Coherent Anti-stokes
Resonance Spectroscopy which is called CARS. How this technique works
is by measuring the actual vibration of the water molecule, (hi-frequency buzzing) and using that vibration
signal, we can actually image it’s presence inside the
cell on a sub-cellular scale. (lo-frequency buzzing) We’ve never been able to see water on the submicron scale, and the question we were addressing was how does the artery work, that is the heart pumps
blood at high pressure throughout your body. Somehow it does that at high pressure without leaks in your arterial system, but we didn’t really know how
the vessel, the artery wall prevented water from leaking out. So these studies using the CARS microscope permitted us to find that there is a very specific position
in the arterial wall where the water is blocked, or prevented from moving forward. What happens is the
pressure in the water move right through the endothelial cell, this barrier to water which sits right on all the large macromolecules that then absorb that energy. So here’s a case where
imaging, you actually saw the process, and in
retrospect you went, wow, that makes sense. And so now that we understand
where that barrier is, we start looking at disease states, what happens when you
have atherosclerosis, does this barrier break down? How are drugs moving? If this is blocking water, one of the tiniest molecules in the body, what is happening when we’re
trying to administer a drug, where is it getting blocked, and where is it getting concentrated? So those are the types of questions that we’re now addressing. There’s a wonderful history
of the Bethesda campus having a tremendous impact on health. Engineers, physicists,
chemists, cell biologists and clinicians all working together, bringing a lot of the
state of the art technology to the understanding of biology, I think that’s one of the
beauties of this program. We let the invetigators
try to find those areas where they could have a
keen insight into biology, keen insight in diseases, and potentially keen insights into therapy, and make our lives a little better.

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