Profile of Clifford Lingwood
Dr. Clifford Lingwood, PhD
- Senior Scientist, Molecular Medicine
- Professor, Departments of Laboratory Medicine & Pathobiology and Biochemistry, University of Toronto
1. Where are you from and where did you study?
I grew up in the UK. I completed my undergrad at Hull University and then my PhD at the National Institute of Medical Research in Mill Hill, London, England.
2. What are you researching right now?
I work on glycosphingolipids which are sugar - lipid conjugate molecules. I work on the more basic members of this family of molecules which are present in all mammals. Because these molecules are conjugates between a lipid and a sugar, there is often ‘tension’ between them because lipids don’t like to be in water and sugars do. This causes a sort of ‘stress’ between them, and because they are dynamic, they can reorganize into different structures very easily when their environment changes.
Glycosphingolipids are considered co-factors in many human diseases. Abnormal glycolipid synthesis can make diseases like cancer, asthma, diabetes, Alzheimers, Parkinsons and rheumatoid arthritis much worse. By blocking glycolipid synthesis, we can reduce disease symptoms. At present, we can only block the synthesis of all glycolipids, but in diseases since only one or two glycolipids are elevated, more selective regulation is more beneficial. We’re working on new ways of regulating glycolipid biosynthesis in order to gain more specific control.
Glycolipids are important in HIV infection too, and we are trying to develop glycolipid-based inhibitors. In fact, we found some glycolipids make cells resistant to HIV infection. Many microbial pathogens (viruses and bacteria) interact with glycolipids, and these interactions can be hijacked to target glycolipids involved in disease. We use this approach to design new treatments for certain genetic diseases, in which mutant proteins do not achieve their correct 3D shape and are broken down, for example cystic fibrosis and Gaucher disease.
3. Who is your all-time favourite scientist, and why?
I would have to say Einstein. We’re a hundred years past his time and we still don’t completely understand what he was saying. He was centuries ahead of his time. Many of his predictions are only now being verified. The guy was a beacon.
4. What in your opinion is the single most important scientific breakthrough, and why?
I suppose the molecular revolution in sequencing and analysis of genetic defects in diseases is the most important scientific breakthrough. Unfortunately genetic sequencing is sometimes done just because it can be done; the technology is often used with little rationale. But nevertheless, there have been some spectacular successes in terms of the identification of genes involved in disease, so that has to be up there! However, the therapy based on the identification of genetic defects has lagged behind. We are not as advanced as we ought to be from the knowledge we have. I think this is because it’s a very complicated puzzle and all things interact and impact other things. Some diseases are extremely complex problems.
5. What are your major interests outside the lab?
I’ve always played hockey and ridden motorcycles. Eight or nine years ago I went on my biggest adventure with my youngest son when we rode all the way to Vancouver. As well, I enjoy spending time with my kids and my grandkids. I don’t see them as much as I would like because they live far away. I am currently building a cottage up north, so that it will be nice to have them visit me there in the summers!
6. Why science?
I didn’t get into it deliberately. I remember I applied for a position as a technician and I was offered to do that or register for a PhD. I decided to register for the PhD and it sort of took off from there. I was always scientifically oriented at school but didn’t have a burning desire to be a scientist. That desire really came in my first post-doc at the Fred Hutchinson Cancer Center in Seattle with a leading expert in glycosphingolipids. That experience really keened me into wanting to be a scientist.
7. Why SickKids?
I first came here to do a postdoc and I have just celebrated 35 years here at the hospital. From learning about glycolipids in Seattle, I thought I should learn about glycoproteins, which are the other sugar conjugates. There’s a world expert here at SickKids, so I figured I would do a postdoc with him, but when I got here, he wanted me to work on glycolipids (in reproductive biology, no less) rather than glycoproteins, so I never really got to work on them.
The key for me at SickKids was way back when the “Hamburger Disease” outbreak occurred in Walkerton, Ontario in 2000. I found the toxin made by this E.coli bug binds to a glycolipid. It is this glycolipid in the kidney that mediates the kidney disease that can occur in infected children. Knowledge of the glycolipid receptor for this toxin helped explain the basis of the disease and spurred investigation to use this therapeutically to prevent symptoms.
This identification also jump started our work into examining how these toxins could be useful for other purposes. We found that cancer cells (particularly drug resistant forms) were more sensitive than non- cancer cells and that this was a potential new way to treat cancer. Others now show that the toxin can be used to deliver cytotoxic drugs more selectively to cancer cell targets.
8. What is the most controversial question in your field right now?
I had planned to retire sometime soon, but there is one significant problem left in glycolipid biosynthesis. There is an unknown mechanism that allows a glycolipid precursor molecule, which is made on one side of a membrane in a cell, to flip over into the other side of the membrane where all the rest of the glycolipids are made.
We’re trying to identify the mechanism that allows this to happen. It’s a problem that has been around for over 30 years, so it would be great to be able to solve this during my time here. We’ve got some clues from some new chemical probes we’ve made that are quite exciting so I want to stick around for a bit longer! If we identify the mechanism, it will provide a new handle on how we can selectively control glycosphingolipid biosynthesis and apply this to diseases.
9. What are you reading right now?
I think in the last 20 years I’ve probably read only two non-scientific books. I keep saying I will save my reading for when I retire. I’m going to sit in a rocking chair on my deck at the cottage I’m building and I’m going to read all the books my wife has read.
10. If you could give one piece of advice to someone considering a research career, what would it be?
It’s important to find a question that you really care about. Science can be a tough job, but if you really love what you do, if you love the question and you care about finding the answer to that question, then it’s no longer work, it’s something you want to do.
11. What does the Peter Gilgan Centre for Research and Learning mean to you?
Think sideways. Don’t follow the steps in order from “A” to “B” to “C” to “D.” You have to think laterally to implicate something you learned outside of your field in order to incorporate it within your field. It’s tough to do but you can make strange correlations and this is where you can get an advantage. Though 90% of the time you will be wrong, there will also be those times you are right.