Primarily in Bangalore I’m working on a wound healing response, basically how does the wound healing work and why does it not work in certain cases, so like in diabetic patients why is there an impaired wound healing response; why doesn’t it close? And eventually that leads to amputation. Part of it came from personal because both my parents passed away with complications due to diabetes so that’s why I went into a little of that field of why does the wound healing response not function properly and why does it lead to the amputation and eventual complications for people with diabetes?
How does this relate to stem cells?
There’s an old hypothesis that was first put up in 1863 by this German pathologist, Birchau, that linked the wound healing response to cancer. So he noticed early on that cancer seemed to form where there was more irritation or injury to tissue. Then more recently in 1978 a Harvard pathologist, Jann Dvorak, he showed that a lot of the processes that occur in cancer such as inflammation, proliferation of stem cells, movement of cells and migrations, look like metastatic cancers. So the idea then is that if you understand the physiological basis of these processes you can understand what goes wrong in cases such as cancer which basically perturbs a lot of these normal physiological processes. So the idea then is that cancer is probably the ultimate perturbation of normal tissue physiology and one way of understanding that process is understanding how does it occur normally and then what switches it to make it react abnormally.
Are you looking at the potential of metformin?
No, not necessarily. I am looking at the inflammatory response so the question then is that in a wound healing response you get inflammation to help fight off the infection because you have a hole in the tissue and microbes have access to it. But the process turns off, so what we’re trying to understand is that in cancer why doesn’t it turn off when it’s supposed to. Again, to understand why doesn’t it turn off we have to understand what is the mechanism that normally turns it off in the first place. So that’s what we’re looking at.
What are the effects on the immune system and dangers?
Dangerous to make broad statements because different cancers have different reactivities to them. So cancer immunosuppression as a therapeutic can also basically affect other things besides the tissue physiology. That’s where this whole systems approach is starting to have an impact on our science is that generally in biology we take a reduction approach, isolating the cells and seeing how they react in isolation but what we’re finding is different signalling pathways by different cells can modulate how one cell reacts to a signal but when it’s in the presence of another cell it has a totally different reaction; it can be either combinatorial or adversarial in nature. So part of what we’re trying to understand, and taking the skin as a model system where you have epithelial cells such as keratinocytes and hair follicles, you have fibroblasts and extracellular matrices, all these contribute to normal wound healing responses and you can find various cancers that either one or multiple of those components are perturbed. So the idea that if we take a systems approach to understand how these work in combination with each other, we’re able to better understand how they go awry in cancer.
What have been some recent advances?
Probably one of the major advances in skin wound healing was that the hair follicle stem cells when you wound the skin can be mobilised, which are normally dedicated to regeneration of the hair follicle, can move up to the epidermis to try to close the hole in the tissue. In the dermis it has also been found that there are many different types of stem cells. They could either come from the blood vessels themselves, from the bone marrow, cells that travel from the bone marrow through those blood vessels, as well as resident stem cells within the dermis.
I guess one of the hot areas in the field right now are these cells that are lining the blood vessels called pericytes. Those have features of bone marrow mesenchymal stem cell features and people are very interested both in their therapeutic value as well as what are their normal physiological contributions to tissue homeostasis or, in our case, wound healing.
