Cellular Trafficking & Polycystic Kidney Disease - The Caplan Lab at Yale School of Medicine

Transcript

• 00:04Epithelial cells are the cells that form the boundary
• 00:07between the inside of you and the outside of you,
• 00:10and as such, they have to do two things:
• 00:12One is they have to prevent you from mixing with the outside world,
• 00:16but also they have to control what you take in from the outside world
• 00:21and what you excrete back into the outside world.
• 00:25There's a top of the cell that faces the outside world,
• 00:29we call that the apical side,
• 00:31and then there are the sides that face the the intracellular fluid or blood space,
• 00:36we call that the basolateral side,
• 00:38and then there's glue that holds those epithelial cells together
• 00:42and prevent stuff from leaking between them,
• 00:45we call those tight junctions.
• 00:47So we're very interested in understanding
• 00:50the structures that are required to mediate function.
• 00:56Part of my lab is studying kidney epithelial cells
• 00:59and trying to figure out how they target proteins to the right places,
• 01:04apical versus basolateral,
• 01:06and how they organize their unique structures
• 01:09in order to carry out their function.
• 01:12The rest of the lab is studying polycystic kidney disease,
• 01:16and there are sort of two sets of projects within that group.
• 01:20One is focused on trying to understand at a molecular and cellular level
• 01:25what is it that the proteins encoded by the polycystic kidney disease genes do?
• 01:30What is their physiologic functions?
• 01:32And the other part of the lab is trying to figure out
• 01:36what are the therapeutic vulnerabilities in polycystic kidney disease?
• 01:40Are there small molecules or gene therapy strategies that could be
• 01:44used to try and fix the disease, or at least slow it down?
• 01:51We use a lot of different microscopy techniques,
• 01:54including immunofluorescence microscopy,
• 01:58electron microscopy, to analyze the kidney and understand its structures.
• 02:03We do a lot of protein biochemistry.
• 02:05We do a lot of molecular analysis
• 02:08and what we're trying to do is put together a holistic picture
• 02:13of what's going on in cells by interrogating
• 02:16all of these different features that allow us to assess whether
• 02:19the pathways and functions that we're exploring
• 02:22and the therapies that we're trying to develop
• 02:25mimics the aspects of the human disease.
• 02:30Like everybody, we're hoping, right, that we're going to develop
• 02:33a new understanding of how nature works in the context of how
• 02:37epithelial cells organize themselves
• 02:40and more immediately, we're hoping that we can identify
• 02:44new mechanisms that are responsible for polycystic kidney disease
• 02:48and, most importantly, new therapies.
• 02:50So our lab has developed a couple of therapies,
• 02:54one of which is in human clinical trials,
• 02:56one of which is hopefully headed towards human clinical trials.
• 03:01The great thing about
• 03:03working on a genetic disease like polycystic kidney disease
• 03:07is it can teach us both about
• 03:09potential therapies and also about fundamental physiology.