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Mending a broken heart

by YPU Admin on December 11, 2014, Comments. Tags: britishheartfoundation, cardiovascular, cells, heart, medicine, Research, and treatment

Introduction

Hi! My name is Abi Robertson and I am a second year PhD student in the cardiovascular group at the University of Manchester. After finishing my A Levels I started an Anatomical Science degree at the University of Manchester. This was where my love for the heart began! Following my undergraduate degree I completed an MRes in Cardiovascular Health and Disease here and this enabled me to apply for a PhD funded by the British Heart Foundation. You can find more information on my PhD and the other cardiovascular courses available here .

My PhD project is called ‘Targeting the Hippo signalling pathway to enhance the protective effects of iPSC-derived cardiomyocytes’ (A bit of a mouthful!). In short this means I am looking at how cells signal within themselves to divide and to see if we can target this to help stem cells become heart cells and survive.

But why?

In Depth..

During a heart attack the blood supply to the heart is stopped. Lack of blood and oxygen damages the heart cells. This can result in a severe loss of cells in sections of your heart. Unlike other tissues in your body, such as your skin, cells in the heart cannot heal themselves. This leaves an area in the heart that cannot beat like the surrounding tissue. This is called an infarct area.  If the infarct area is quite large it can affect how your heart functions, leads to health problems and even heart failure.

For the heart to be able to function normally again the heart cells need to be replaced. Attempts are being made to heal the heart by creating heart cells in the lab from stem cells. Using new technology we can re-programme skin cells into stem cells. The skin is an excellent source of cells as they are easily available. These stem cells are called Induced Pluripotent Stem cells. These cells can then be turned into any cell type in the body including the beating cells in the heart. The hope for this therapy is that these cells can be used to make patches and be placed on the heart like a plaster.

Before this is possible we need to make sure the heart cells we are using are able to survive in the challenging environment of the infarct area. Firstly, the infarct area has low oxygen and nutrients, so the cells need to be able to cope with this. Secondly, it is estimated over a billion cells are lost after a heart attack so a lot of heart cells are needed!

This is why my PhD project is looking at the signalling within cells and seeing if we can create cells which survive but also divide in tough environments. We hope to create super heart cells!


Going further..

I really enjoy working in this area of research. It’s a relatively new area so there are always lots of exciting discoveries! Hopefully one day using stem cells as a therapy will become the treatment of choice for people who have suffered a heart attack!

Here are a few links if you would like any more information on the area:

The Stem Cell Network has created some excellent videos on ‘What are stem cells?’

http://www.stemcellnetwork.ca/index.php?page=what-are-stem-cells

Explore an interactive comic about stem cells:

http://www.smm.org/tissues/stem_cells.php

An excellent TED talk by Susan Soloman on the use of induced pluripotent stem cells:

http://www.ted.com/talks/susan_solomon_the_promise_of_research_with_stem_cells?language=en

The National Institute of Health has an excellent website that covers pretty much everything you could want to know about stem cells:

http://stemcells.nih.gov/info/basics/pages/basics1.aspx

A stem cell story:

http://www.eurostemcell.org/films/a-stem-cell-story/English

YouTube user John Schell has some great videos of beating heart cells that have been derived from Induced Pluripotent Stem Cells:

http://www.youtube.com/watch?v=5uvNPQDDbAc

This BBC article discusses a clinical trial that is underway to see if stem cells can heal broken hearts:

http://www.bbc.co.uk/news/health-26273707


 

Pondering Podocytes

by YPU Admin on June 19, 2014, Comments. Tags: biology, medicine, and Research

Introduction

My name is James McCaffrey and I am doing a medical PhD. I went straight into medical school after finishing my A-levels, and graduated in 2007. I continued my training as a junior doctor in Manchester before deciding to specialise in paediatrics in 2009. After a few years of being a paediatric doctor, I became interested in children’s kidney disease and began a PhD at the University of Manchester in 2011.

My PhD focuses on a childhood kidney disease called ‘nephrotic syndrome.’ The medication we have for treating nephrotic syndrome only works for a proportion of children, and sometimes results in unwanted side effects. No one knows exactly how this medication works. By trying to understand more about the important actions the medication has in children with nephrotic syndrome, we may be able to develop more effective drugs with fewer side effects in the future.


In Depth

What is nephrotic syndrome?

One of the main functions of the kidney is to filter the blood, so unwanted substances can be removed from the body. However, it’s also vital that the kidney filter does not let important proteins and minerals leak through. An essential part of the kidney filter is a cell called the podocyte, which keeps blood proteins in the body, while letting substances harmful to the body pass through.

In nephrotic syndrome, the podocytes become damaged and the kidney filter becomes abnormally leaky, so these important blood proteins are lost from the body. These proteins help regulate where water is stored in the body and are needed to fight infection. When they are lost in nephrotic syndrome, children have a high risk of developing serious infections and water moves from the blood into various tissues so patients develop massive body swelling. 

How is nephrotic syndrome treated?

Children with nephrotic syndrome receive an 8 week course of a type of steroid called prednisolone (this is very different to the steroids body-builders use!). Some children respond very well to this treatment, the kidney filter returns to normal, and they never have the disease again. Some children respond well initially, but the disease comes back several times over a number of years. Unfortunately, some children do not respond to steroids at all, and more powerful medications are needed. The children who do not respond to steroids during their first treatment course sometimes have long term problems with their kidney.


Why is nephrotic syndrome important?

Approximately 200 new children develop nephrotic syndrome in the UK every year. As late as the 1950’s approximately half of children with nephrotic syndrome died (mostly from infections). Although today we have more effective treatments available, children taking steroids sometimes experience unwanted drug side effects such as weight gain, high blood pressure and acne. Children who do not respond to steroids have a high chance of developing long-term kidney problems, which may ultimately require kidney transplantation.

What do I investigate?

Although steroids have been used in nephrotic syndrome for many decades, no one knows exactly how they work! It’s also unclear why some children respond well to steroids, while others do not. I mainly work on podocytes grown in the laboratory and characterise their response when they are treated with steroids. This involves finding out what new proteins are made when podocytes are treated with steroids, and investigating whether any of these may be important in the response that the kidney filter has in children with nephrotic syndrome when they receive medication.

Steroids do a lot of things: some of them helpful to the kidney barrier, and some of them unhelpful (which is why children experience side effects). If we could understand more about the helpful actions that steroids have in nephrotic syndrome, we may eventually be able to make drugs that are effective for all children with nephrotic syndrome and also have fewer side effects.

Going Further

More information about nephrotic syndrome from a patient’s perspective can be found here (http://www.nstrust.co.uk/pages/home/aboutns)

Here’s a great website for finding out about all the kidney research happening in Manchester (http://www.gmann.co.uk/website/index.cfm)

An explanation of other projects happening in my PhD supervisor’s laboratory can be found here (http://www.wellcome-matrix.org/research_groups/rachel-lennon.html)

Here are some PhD projects that doctors in the North West are currently working on (http://www.liv.ac.uk/north-west-england-mrc-fellowship-cpt/fellows)