Published on 13 Aug 2017.
Tagged:
publication
exosomes
I've studied exosomes since the Summer of 2007 when I did my MSc dissertation project and then PhD in the laboratory of James Dear. When it came time to move on I was fortunate in finding my current position where I could explore new areas without moving away entirely from the exosome field where I had so much experience.
An opportunity to revisit the exosomal field came at the beginning of 2016 when we were invited to write three separate book chapters and review articles on exosomes. The third manuscript, a chapter in the book "Drug Safety Evaluation", has just been published online.
Inevitably the manuscripts have some overlap but they each focus on different aspects of exosomes and their study. The highlight was having a figure from our article in the journal of cellular physiology on the front cover of the issue.
The three manuscripts are:
Urine Exosome Isolation and Characterization is focused on the methods we use to collect, process, and characterize exosomes.
Urine Exosomes: An Emerging Trove of Biomarkers is a review of the potential and challenges in bringing exosome based biomarkers into clinical use.
Quantification of Exosomes is a review of the options available for determining the concentration of exosomes.
Published on 29 May 2017.
Tagged:
python
keras
openslide
shapely
deep learning
microscopy
At the NIH Pi Day celebration I gave a lightning talk on applying deep learning to histology images. A video of the event is now available at NIH Videocast.
During the one hour event there were presentations on ten different projects. I was the second speaker and began at 8:48.
I am using deep learning to identify glomeruli in kidney biopsies. When we are unsure about the specific type of kidney disease a patient has we take a small biopsy to look at the kidney. It is often differences in the glomeruli that define the type of disease. Pathologists study the biopsy to define the type of kidney disease. These skilled pathologists spend significant time locating the glomeruli. A machine can do this simple step. The pathologist can then focus on the harder disease identification task.
Published on 08 Mar 2017.
Tagged:
python
openstreetmap
OSRM
The theme for the Transportation Techies event this month was Capital Bikeshare. This is the bike sharing service in Washington DC. Information is available on every trip and every station. Lots of analyses are possible with all this data. This event was the seventh on this theme.
I had not worked with geographical or transportation data before this so I learned a lot. I treated the stations as cities in the traveling salesperson problem. I then calculated the shortest path visiting all the stations.
I was able to do this using open data and open source software. This included customizing the calculation of distances for cycling.
The slides I presented include links to all the data and software used. The code I wrote is available on github. I include a Dockerfile for running the routing software with data for the Washington DC region.
Published on 02 Dec 2016.
Tagged:
publication
exosomes
A lipid bilayer, called the plasma membrane, surrounds every cell. This protects the cell from the environment and keeps the insides in. Keeping material contained is important for many aspects of biology. Lipid bilayers form organelles and vesicles within the cell to contain specialized components. For example, powerful enzymes recycle old material in the cell. If not contained these enzymes would wreak havoc. To prevent this lysosomes contain the enzymes, protecting the cellular contents. Material from all over the cell can get added to lysosomes.
Vesicles move material from one place to another. Endosomes move material from the plasma membrane. Endosomes either fuze with lysosomes or recycle back to the plasma membrane. The lipid bilayer of an endosome will join with the plasma membrane. The contents of the endosome exit the cell. The endosome can contain even smaller vesicles. Outside the cell we call these vesicles exosomes.
During my PhD I discovered that exosomes can transfer proteins between kidney cells. Wilna Oosthuyzen continued this work by asking what regulates this process. She discovered that vasopressin regulates exosome uptake in collecting duct cells of the kidney.
It is very gratifying when a study builds on work I published earlier, and particularly when executed so well. I was very pleased to be able to contribute.
Published on 27 Jun 2016.
Tagged:
publication
sepsis
In an earlier post (TLR4) I discussed the TLR4 receptor. This receptor detects microbes and starts an inflammatory response. TLR4 is not the only receptor that detects microbes. There are many receptors the immune system uses. This redundancy prevents microbes going undetected and matches the response to the microbe. At least, when everything works. An excessive response can cause sepsis. In sepsis the response is so strong that it damages tissues and can even cause organ failure.
I have recently collaborated with Oliver Voss and John Coligan from the National Institute of Allergy and Infectious Diseases. They were studying CD300b. This is another receptor that binds lipopolysaccharides (LPS) like TLR4. CD300b then binds to TLR4 and enhances its signaling. This enhanced signaling can then cause more tissue damage, leading to sepsis.
Inhibiting TLR4 does not work well for treating sepsis in humans. This might be because some TLR4 signaling helps combat infecting microbes. Inhibiting CD300b might strike a healthy balance between continuing to fight the infection and the excessive signaling causing tissue injury.