Diabetes around the clock for Cecilia Holm
There are no bangers and mash in the lunch room at BMC in Lund, where Professor Cecilia Holm works. However, her interest in food doesn’t end with a healthy and tasty lunch.
“We don’t content ourselves with knowing that certain foods make you thin and healthy. We also want to explain the molecular mechanisms behind this phenomenon, and there are major gaps in our knowledge”, says Professor Holm.
However, it is only in recent years that Cecilia Holm’s research has focused mainly on food. When the Antidiabetic Food Centre started in 2007, as a ten-year project jointly funded by Vinnova, the food industry and Lund University, the research to prevent diabetes and obesity was focused on various food concepts. One of Cecilia Holm’s doctoral students, Ulrika Axling, started a project on the various health benefits of rose hips, which showed that concentrated rose hip powder in the food of mice led to lower blood sugar levels, less fat in the liver and lower cholesterol. Unfortunately, the results in humans were not as good.
“Nonetheless, we observed a lowering of LDL cholesterol (the ‘bad’ cholesterol) and lower blood pressure”, says Cecilia Holm.
Kitchen turned into a lab
However, it wasn’t food that led Cecilia Holm into a career in research, even if she did happen to do a project on vitamin C in secondary school. The kitchen worktop at the family home in Malmö was transformed into a provisional laboratory, where she performed experiments to see how different foods maintained their vitamin C levels.
Initially, she was convinced she wanted to be an architect, but she kept the idea a secret, hiding her drawings from friends when they came round.
A study adviser told her that the job market for architects was limited, and thought that with her good grades, Cecilia ought to apply to study medicine.
“When I was at school, I was already interested in scientific research. I was heavily involved in the ‘Young Researchers’ organisation.”
She found maths and physics fun, but biology and chemistry were even more fun.
Knows every post code in Sweden
Cecilia Holm describes herself as having been very independent and conscientious since childhood (“I’ve always been a bit of a workaholic”). In her late teens, she spent a year on an exchange in Maine in the north-eastern USA. There, she attended a girls’ school, got involved in athletics, learnt to drive and went skiing a lot. She wasn’t homesick at all.
At the weekends and during school holidays, she worked as a postwoman and at the sorting office.
“I still know every postcode in Sweden. They’re etched on my memory...”
Sights set on research
On leaving school, she followed the recommendation of the study adviser and applied to do medicine at Lund University, but from the very start she had her sights set on a career in research.
“I ordered a book that described all the research projects, and read it from cover to cover. I was interested in enzymes and found a project with Per Belfrage.”
She went to see Per Belfrage in her first week, but to her great disappointment he was away in the Canary Islands.
“I didn’t think that seemed very professional”, she says with a smile.
Instead, she bumped into Gudrun Edgren, who explained what they were doing. She was very enthusiastic, because the group had just managed to isolate an enzyme (hormone-sensitive lipase, HSL) after decades of work, and an article on the discovery had been published.
To Cecilia’s delight, she was given a project to work on alongside her studies for three years, and got to share a lab with Eva Degerman.
Wanted to be the first in the world
In those days, the medicine programme was structured differently, and it was natural to take a year out after three years. At that point she was admitted as a doctoral student and started to do research full-time. During her penultimate year of research studies she started to make real progress and became determined to be the first in the world to clone the HSL enzyme.
Today, we know that HSL is found almost everywhere, from fat tissue to muscle and all steroid-producing tissue, testicles and adrenal glands. HSL is required to break down the fat in fat tissue and is regulated by insulin. Working with Patrik Rorsman and Bo Ahrén, she later realised that the lipase was not only in the fat tissue, but also in the beta cells that produce insulin. Many articles have since been written about HSL’s role in the beta cells, and HSL has been named as a target for anti-diabetes drugs. When the enzyme is removed in experiments on animals, the males become sterile, which has led many researchers to try and develop a male contraceptive pill using HSL.
Personal relationships and network
However, back to the challenge of cloning the enzyme. The importance of personal contacts and networks cannot be understated.
Thanks to Per Belfrage’s contact with Professor Michael Schotz, who had previously been a postdoctoral fellow under Bengt Borgström (“the great professor” at the division and “the father of lipase”), Cecilia got the chance to visit Schotz’s lab in the US and learn about molecular biology.
“It was a brilliant opportunity, by far the most instructive year of my career”, says Cecilia Holm, and goes on:
“I learnt loads about molecular biology, broadened my knowledge and got to know a lot of people; it was fantastic.”
The collaboration led her to become the first person to clone the HSL enzyme and her work was published in the journal Science.
It also opened up new questions, and gave her a dream opportunity when she finished her PhD in 1989. She was able to start a four-year postdoctoral research post and develop her own research group in lipid metabolism.
Diabetes the common denominator
The research on HSL and obesity led to an increasing number of collaborations where diabetes was the common denominator, including collaborations with the Antidiabetic Food Centre. Today, she is trying to approach the problem from two angles.
“I do both research on what we should eat to prevent obesity and type 2 diabetes, and research that could generate a basis for new drugs.”
One of her new research projects is about vitamin D, which those of us living at northern latitudes often lack in the winter because of a lack of exposure to sunlight.
“Many studies have shown that obese people suffer from vitamin D deficiency. We wonder whether fat tissue plays a role in this. There are theories that vitamin D is captured and stored in fat tissue, and the question is whether this is a good or a bad thing. There are also studies that show that vitamin D can play a part in insulin release and insulin sensitivity. However, there is still a lot we don’t understand in this area.”
Life was turned upside down
Six years ago, life was turned upside down for Cecilia Holm and her family when her three-year-old son developed type 1 diabetes. Three and a half years later, her then twelve-year-old daughter also developed the condition.
“It was a shock, but we were prepared because the children had been involved in the TEDDY and DiPiS studies and were identified as having antibodies at an early stage. My career has obviously been useful to me in managing the disease as a parent because I know about the physiology behind it and a lot about insulin and insulin treatment.”
Even if both children have dealt with the situation extremely well, according to Cecilia, the diabetes is nonetheless always present.
“You can’t understand what it’s like if you’re not in the situation yourself. You have to be available 24 hours a day and always on call. It’s extremely rare for anything to occur; it might happen that the school rings to ask for advice. My daughter is better at counting carbohydrates than most people I know, but the difficult thing is predicting how much exercise she is going to do. It’s a difficult equation to solve.”
Course director on medicine programme
The experience of having children with diabetes has spurred her on in her work and has given her an even stronger motivation. In order to better manage her time, she decided to become a course director on the homeostasis course (“about balance in the body; how it works from a physiological perspective and how hormones control everything”), which runs for a whole semester on the degree programme in medicine.
“It’s great fun – a lot of administration and a lot of issues relating to teaching.”
In addition, she is also a member of a group working on the reform of the medicine programme, and sits on the faculty’s Board of Biomedical, Medical and Public Health Education.
“I’m involved in a lot of sideline activities, which is fun. It’s a healthy mix and I meet lots of pleasant students and colleagues whom I wouldn’t otherwise encounter.”
Research that benefits patients
When asked about her future research, Cecilia Holm says:
“I think more in terms of how I can do something to really help people with diabetes. We mustn’t forget that what we do has to bring real benefit to patients.”
Outside her research, she dreams of one day opening a health food café or restaurant, where guests are served what is understood to be healthy food and can also listen to talks about research.
When she eventually retires and looks back at her career, she hopes she will be able to think “we were the ones who realised…” or that she has laid the foundation for a new drug.
“But it’s a continual process. If there haven’t been any new drugs or dietary advice, at least I will have paved the way for someone else.”
Text: Sara Liedholm/Hannah Mellors