NEW PROFESSOR. Lund researcher David Bryder, who has made pioneering discoveries regarding blood stem cells, now resides at the Sahlgrenska Cancer Center at Medicinareberget. The translational environment, and the good opportunities for cooperation with clinical researchers was, first and foremost, what attracted him here.
“I have had a good time in Lund. I started my researcher group there over ten years ago. But I think it is important to do new things and have always enjoyed the prospects for new collaborations,” David says when I meet up with him in his office at the Cancer Center.
We meet up on a Friday and that is not by chance. His family has already moved to Gothenburg and his son has settled down well in his new High School but, during the week, David is still spending much of his time in Lund where he leads a successful and active research group. In Lund, David also keeps his mouse lines, many of which he has developed himself, and which soon are to find a new home in Gothenburg.
How the blood is formed
David Bryder gained his doctorate in Lund in 2003 and did his postdoc at Stanford in California. In Lund his research is conducted with the aid of several research grants, including among others, ERC, Knut and Alice Wallenberg’s Foundation, The Swedish Research Council and The Swedish Cancer Society.
He is primarily interested in what happens when stem cells in the blood mature into different types of blood cells and what happens when individual stem cells are maintained. The blood stem cells provide the source of billions of new blood cells every day – the red cells which carry oxygen, the platelets which cause blood to coagulate and our immune cells which protect us against infections.
The different types of cells in the blood are developed via hierarchies where all cell types must pass through several stages of differentiation before they are fully matured. In his research, David maps different factors which control how this happens. It is basic research but it is relevant to important clinical questions, first and foremost regarding leukemia and other blood-related diseases.
“Leukemia does not normally occur in mature cells but rather in immature ones which have lost the ability to continue their maturation, but which have retained their ability to multiply,” says David Bryder.
Among the immune cells there are some which have a very short lifespan which counteract infections, and another group of cells – lymphocytes – which live longer and which specialize in countering specific bacteria and viruses. As recent as last week, his group had a new article published in Cell Reports in which they identified that the HLF gene, which is normally only expressed in immature blood cells, must be shut down in order for lymphocytes to be generated. If the gene is not turned off, we only generate the more short-term immune system.
“Patients with leukemia in which the HLF gene is involved have a very poor prognosis, but it has been difficult to generate reliable models for studying the occurrence, progression and possible treatment of these leukemias more thoroughly,” says David Bryder.
Old and young cells
Another research line in David Bryder’s laboratory concerns how the blood stem cells change as they grow old. He tells of a spectacular study made by a PhD student in his group, Martin Wahlestedt, who investigated the stability of old blood stem cells. Martin took blood stem cells from an old mouse, marked them individually with a unique molecular barcode and then transplanted them into young animals whose own blood systems had been eradicated. The old cells were then allowed to construct a new blood system where the contribution from each individual cell could be evaluated by means of the barcodes. Then those cells were selected which had barcodes associating with functional aging. These were re-programmed to embryonic stem cells and, in their turn, used to clone new mice.
“We observed that all the clones we characterized behaved entirely like young ones. Since it is possible to regain functions that a cell had previously lost, the study says something about the mechanism. If aging had been driven by damage to DNA, then this would have persisted also in the re-programmed cells,” says David Bryder.
Even though he is not himself an MD, he has always worked together with clinical researchers and this is something he hopes to develop further now that he is taking his research to Gothenburg.
“For example we are working with models for acute leukemia and are keen to cooperate with people who encounter this type of patients. It is both a question of gaining access to relevant patient material as well as discussion and input concerning what are clinically relevant questions,” says David, and continues:
“Such collaborations are also, of course, about what we are able to contribute with. One challenge is to keep up with the rapid development in experimental techniques and models and, in this respect, we have an advantage in that we do not have to divide our time between research and patient care.”
He believes that it can also be a matter of an alternative or complementary approach towards research:
“It may be that we, with our background in basic research, have more experience in establishing causality, rather than the retrospective approach which usually has to be made when treating patients.”
TEXT AND PHOTO: ELIN LINDSTRÖM CLAESSEN