Endothelial Cells, Lung Biology, & Signaling - The Niethamer Lab at Yale School of Medicine

Transcript

• 00:04Endothelial cells are thin, flat
• 00:06cells lining the blood vessels
• 00:08that deliver oxygen and nutrients
• 00:09to our tissues, but endothelial
• 00:11cells aren't just a structural
• 00:13component of this passive conduit
• 00:15of oxygen and nutrients, they're
• 00:17actually interacting with their environment.
• 00:19So, they receive signals from
• 00:21cells in their niche and
• 00:22they signal to other cells
• 00:24and that can help build
• 00:25organs,
• 00:26pattern tissues during development, but
• 00:28it can also drive some
• 00:29maladaptive processes like fibrosis or
• 00:32cancer and can participate in
• 00:33disease progression. So these cells
• 00:35are really important,
• 00:37components of the microenvironment
• 00:39in most tissues.
• 00:43We are a vascular biology
• 00:44lab and we're particularly interested
• 00:46in the lung endothelium
• 00:47and what we'd like to
• 00:48understand is how these cells
• 00:50do signal with other cells
• 00:51in the lung to build
• 00:52and rebuild three-dimensional structures. But
• 00:55we don't understand a lot
• 00:56about how it's regulated. Regulated.
• 00:58We don't understand a lot
• 00:59about how it's put together,
• 01:00how it's maintained,
• 01:02and how it's repaired during
• 01:04injury or disease. And so
• 01:05we're interested in understanding
• 01:07how endothelial cell signaling contributes
• 01:09to those processes.
• 01:13We are interested in a
• 01:14number of different ways that
• 01:16endothelial cells contribute to the
• 01:18lung, so we have to
• 01:19understand
• 01:20which endothelial cells are present,
• 01:22so we spend a lot
• 01:22of time thinking about different
• 01:24types of endothelial cells that
• 01:26maybe express different genes or
• 01:28perform different functions in the
• 01:29lung,
• 01:30and how those cells might
• 01:31change with injury or disease,
• 01:32and then how that might
• 01:33change their signaling behavior.
• 01:35So to study that, we
• 01:36do a lot of genetic
• 01:38models where we can manipulate
• 01:39these signaling molecules that these
• 01:41specific types of endothelial cells
• 01:43express.
• 01:44We also love imaging, so
• 01:45anytime we can get a
• 01:47beautiful two dimensional or three-dimensional
• 01:49image of endothelial cells, of
• 01:51overall vascular structure in the
• 01:53lung, and of how these
• 01:55cells are interacting with other
• 01:56cells, we really enjoy that.
• 01:58And then because we're interested
• 01:59in cell subtypes, we also
• 02:01do a lot of flow
• 02:01cytometry,
• 02:02to identify different cell types.
• 02:07We know now that vascular
• 02:09dysfunction is a component of
• 02:11lots of different lung diseases
• 02:12and so that includes
• 02:14acute acute lung injury that
• 02:15might happen through respiratory infections,
• 02:17chronic lung diseases like COPD
• 02:19or IPF, and then of
• 02:21course, lung cancer is the
• 02:22leading cancer cause of death
• 02:23worldwide. So I think there's
• 02:25a lot of opportunity
• 02:26to apply this knowledge, to
• 02:28understand how the endothelium contributes
• 02:30to normal lung function,
• 02:32how that might go awry
• 02:33in disease, and how we
• 02:34can maybe manipulate endothelial cells
• 02:36that are behaving badly to
• 02:38move more back towards their
• 02:39normal function and to help
• 02:40with lung disease.
• 02:43Regenerative therapies are really slim
• 02:46for lung disease. Right now,
• 02:47a lot of treatments for
• 02:48these diseases are treating symptoms.
• 02:50It's really exciting time in
• 02:52the lung biology field. We
• 02:53see a lot of new
• 02:54regenerative therapies being developed and
• 02:56tested, and so we'd like
• 02:57to help contribute to that
• 02:59by understanding the endothelial piece
• 03:00of the equation.