NIH Pi Day 2017

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.

Transportation Techies: Capital Bikeshare TSP

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.

Regulation of vesicle uptake

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.

Inflammatory responses to 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.

Chronic kidney disease and lipid metabolism receptors

Lipids are very important molecules in the human body. Different types of lipids include fats and some vitamins. Lipids form the membranes in and around cells, store energy, and signal between cells. Lipids, like fats and oils, do not dissolve in water. To get them around the body they form complexes with proteins. These complexes include LDL and HDL.

Your doctor may have requested blood tests for these. They are important in cardiovascular disease. To get lipids into cells receptors must bind the lipoprotein complexes. Sometimes rather than supporting the cell, lipid uptake can cause stress and inflammation. This is why doctors often check the levels of LDL and HDL.

CD36 is a receptor for lipoproteins. We investigated the role of CD36 in chronic kidney disease (CKD). Breaking this receptor by changing the DNA that creates it protected against CKD. Similar protection happened with a small peptide inhibitor. This is important because it is easier to help patients by giving them a drug than by trying to change their DNA.