Angiogenesis on Michael’s Domain

Inauguration of the new professors

Thu, 28 May 2026 00:00:00 +0000

We - the new professors in the Faculty of Pharmacy at the University of Helsinki - gave our inaugural lectures yesterday!

Angiogenic doping - doable and difficult to detect

Thu, 21 May 2026 00:00:00 +0000

Less than 1% of athletes test positive for doping in typical world-class events (World Championships, Olympics). However, we know that at least 70% of the athletes are doping . How do we explain this discrepancy? My lab does angiogenesis research, i.e., we study the growth of blood and lymphatic vessels. Ever since the discovery of VEGF-B by Birgitta Olofsson and Ulf Eriksson in 1996 , I suspected that VEGFs could make for good doping agents, sooner or later. Anti-doping research in endurance sports has focused on blood and red blood cells (RBCs). Erythropoietin (EPO) doping shows how important the RBCs are. But considering the basic mathematical equation “concentration = mass divided by volume” tells us immediately that you can increase the RBC mass without increasing the RBC concentration by increasing the blood volume. Unsurprisingly, blood volume is very important for endurance performance, perhaps even more so than RBC concentration. This can be seen in “sports (pseudo)anemia”, where some athletes have a relatively low hemoglobin concentration despite unimpaired performance. What is the upper limit of the blood volume? And would it be possible to increase the upper limit by growing more blood vessels? We discuss Angiogenic Doping in our latest publication in Sports Medicine . Our hypothesis is that angiogenic doping might already be in use without any good possibility for WADA to detect it. VEGF growth factors are likely not yet used because their application requires advanced medical technologies that only a few laboratories can provide. However, there are quite a few small molecules that can be slowly up- and microdosed to stimulate both angiogenesis and RBC production in sync, thus avoiding major impacts on the athlete’s biological passport. Thanks go to Sofie Lehto, who laid the groundwork for this study, and to doping researcher and sports physician Sergei Iljukov for continuing to work on this side project with me over the last two years.

KLK3: tumorigenic or not?

Wed, 22 Dec 2021 00:00:00 +0000

We have just published our latest review about the role of KLK3 as an activator of VEGF-C and VEGF-D in prostate cancer . Prostate cancer is one of the most common cancers in males. It is not a question of whether you will get it but only when. Once you reach your 80s, the likelihood of you having prostate cancer is bigger than not having it. In a 2013 autopsy study of Japanese males , who died of other causes, 59% of those older than 80 had prostate cancer. It is likely that many of these cases were indolent and would never have caused any problems. Only a few of them might have become symptomatic had these men lived longer. So, there is a significant interest in distinguishing those cancers that are going to cause problems. Many prognostic markers have been proposed to do exactly that: to predict which cancers would become problematic.From the vascular biology point of view, angiogenesis and lymphangiogenesis are two hallmarks of cancers that have been previously proposed to have prognostic value. When we stumbled upon the fact that prostate-specific antigen (PSA, also known as KLK3) is able to activate VEGF-C and VEGF-D , we thought that this might have significance for prostate cancer. Meanwhile, further research has clarified some questions, and it really seems to be that both VEGF-C and VEGF-D are involved in cancer progression. it is not clear yet which proteases are responsible for the activation of VEGF-C and VEGF-D in real human cancers. KLK3- or Cathepsin D (CTSD)-activated VEGF-D might be a possible cause of the resistance of tumors to bevacizumab (Avastin) treatment. The consequences of VEGF-C activation, on the other hand, are more difficult to predict because activated VEGF-C does simultaneously both good and bad: On the one hand, it facilitates metastasis. On the other hand, it enables an enhanced immune response against the tumour. Interesting research lies ahead. Read more in our review: https://doi.org/10.3390/ijms222413545

Re-purposing the growth factor VEGF-C

Sat, 22 Jun 2019 00:00:00 +0000

An eLIFE digest features our recent publication about VEGF-C ( https://elifesciences.org/digests/44478/re-purposing-the-growth-factor-vegf-c ). Even though our research did not deeply delve into the function of VEGF-C during reproduction, the reviewers comments and our answers (under the “Author response” heading) give more insight than the publication itself. We did not include the sperm motility data in the manuscript. Although sometimes stunning in its magnitude, we did not always measure increased sperm motility in response to active VEGF-C. As is common knowledge, sperm as a biological sample is of highly fluctuating consistency and quality. Interestingly, a paper in eLIFE published two years ago gives some additional insight in what we might be dealing with: Sperm competition risk drives rapid ejaculate adjustments mediated by seminal fluid . This paper shows that the swimming speed of sperm is rapidly regulated by males depending on the social situation (presence of a female or a male competitor). Imho, such factors seem to be almost impossible to control when dealing with human samples…However, the title ambiguously also refers to cancer. Based on our data, we speculate that VEGF-C can be repurposed from being lymphangiogenic to being angiogenic, and further, to be metastasis-promoting.

KLK3/PSA and cathepsin D activate VEGF-C and VEGF-D

Sat, 18 May 2019 00:00:00 +0000

Prostate-specific antigen (PSA) is well known - at least among older males - as a prostate cancer marker, but few people know its physiological function: Sperm cells are trapped in fresh ejaculate, which has a jelly-like consistence. In order to release the sperm cells, the ejaculate needs to be liquefied and precisely this liquefaction is the task of PSA.Also surprising for many people is the fact, that scientists still do not know why high PSA levels are associated with prostate cancer. In our latest research published yesterday in eLIFE , we have made a big step ahead in understanding the role of PSA in both reproductive and cancer biology.It appears that PSA (aka as kallikrein-related peptidase 3 - KLK3) and another enzyme called cathepsin D can activate two growth factors which have been implicated in cancer progression: VEGF-C and VEGF-D . These growth factors do likely contribute to tumor angiogenesis and tumor lymphangiogenesis. By inducing angiogenesis - the growth of blood vessels - the tumor ensures its own supply with nutrients and oxygen. Such blood supply is necessary for a tumor to grow beyond the size of a few millimeters. Likewise, tumor lymphangiogenesis happens when the tumor induces the growth of lymphatic vessels and it is tightly linked to the lymphatic spread (metastasis) of the tumor.Both VEGF-C and VEGF-D are produced as inactive precursors (pro-VEGF-C, pro-VEGF-D) and need to be activated in order to induce the growth of blood or lymphatic vessels. With ADAMTS3 , we have identified the enzyme that activates VEGF-C during embryonic development - which also requires vessel growth - in 2014 ( Jeltsch et al. ). However, it remained unclear whether the same enzyme is responsible also for pathological vessel growth. Now it seems likely that patholigical vessel growth uses different enzymes and PSA and cathepsin D have become prime suspects. Our next experiments will test whether we can slow down or halt cancer growth by blocking these enzymes.

1000+ citations

Wed, 15 May 2019 00:00:00 +0000

The first among my publications to brake the 1000 citations-barrier was Gerhardt et al. 2003 . With the “tip cell concept”, it set a paradigm for vascular biology research: Not all endothelial cells are equal and the tip cell is a specialized cell that marks the forefront of the angiogenic sprout. However, my contribution was limited (number 7 out of 11 authors): I produced most of the proteins that were needed for the study. This spring, Jeltsch et al. 1997 crossed the first time the 1000-citation mark. The paper describes a mouse, that overexpresses VEGF-C in the skin. It is the first ever in-vivo demonstration of a lymphangiogenic growth factor. Although not setting any paradigm, it marks the start of the molecular era in lymphatic research . What percentage of papers achieve 1000+ citations? That differs between disciplines, but e.g. according to https://en.wikipedia.org/wiki/Citation_impact on average it is less than 1 in 4000. Compare this to the average paper, which receives 7.8 citations. And even this average is heavily influenced by a few highly-cited papers ( similar to the Impact Factor ). The median number of citations is 4, meaning that about half of all papers have less than 4 citations (see here ).

Angiogenesis landmark publications

Thu, 09 Mar 2017 00:00:00 +0000

According to Nature, our Science paper from 1997 is a landmark paper for the angiogenesis field: *“A paper establishing the role of VEGF-C and VEGF-R3 signaling in lymphangiogenesis. A new field is born."*The collection of landmark papers for the angiogenesis field from the last 80 years ( http://www.nature.com/focus/angiogenesis/classics/vegf.html ) was published first in 2003 and unfortunately has not been updated to include later seminal studies. However, until today, most of these 86 papers are still must-reads for every PhD student in the angogenesis field.

A Nobel Prize for angiogenesis research?

Sun, 27 Oct 2013 00:00:00 +0000

In 2008, during a dinner in Stockholm (when I participated in the Novo Nordisk Foundation 8th Annual Conference on Vascular Biology in Diabetes Complications) I proposed to Christer Betsholtz to award the Nobel Prize to the world-wide community of postdocs, which are the unsung heroes of today’s research. But the Statutes of the Nobel Foundation forbid to award the price to more than three people. However, statutes can be changed and the Nobel Foundation did exactly that 40 years ago when they stopped awarding the price to dead people. And in this changing world, less and less discoveries and inventions are made by individuals. But here’s my newest proposal, which adheres to the rule of maximally three: Kari Alitalo is probably the only Nobel Prize worthy researcher in the country where I work (Finland). Seriously: after Judah Folkman has passed away, there are not many options to award the prize to somebody from the angiogenesis field. Judah Folkman was the father of the hypothesis, that all tumors should be treatable by anti-angiogenesis ( Folkman J. Tumor Angiogenesis: Therapeutic Implications. New England Journal of Medicine. 1971;285(21):1182–6 ). The Nobel Prize committee missed that chance. And because the field has already significantly contributed to the treatment of cancer (and arguably will still contribute much), it is not so far off to think of a shared prize for the discoverers of the VEGFs. VEGF was discovered more or less independently by several research groups around 25 years ago, among them Napoleone Ferrara ’s and Harold Dvorak ’s. Most notably, Ferrara’s group at Genentech continued the research most successfully until today resulting in the first antiangiogenic cancer drug in 2004. While the discovery of VEGF and the resulting angiogenesis research was not dependent on any single lab, the lymphangiogenesis field was essentially single-handedly re-invented and brought into the molecular era by Kari Alitalo in the years following 1995 - after it had become senile and was lingering without any significant progress since the 1960s. A shared prize to Ferrara, Dvorak and Alitalo? There is an anti-VEGF-A cancer drug on the market and the only thing lacking is a successful anti- or pro-VEGF-C drug. Both are in clinical trials as of this writing ( anti-VEGF-C , pro-VEGF-C ).

Dissecting Lymphangiogenesis and Angiogenesis

Fri, 07 Sep 2001 00:00:00 +0000

The presentation slides below are for some reason extremely slow to load (about 2 minutes). You need to be very patient! Flash support has been ended by all current browsers, and this page uses Ruffle , a Flash Player emulator written in Rust, to resurrect these dead files.

Kloster Seeon Conference (October 1-4, 2000): Exploring the VEGF protein space

Wed, 01 Nov 2000 00:00:00 +0000

I participated in the first International Kloster Seeon “Angiogenesis” Meeting" https://www.vwfb.de/seeon-meetings in Germany, with a poster about VEGF growth factors. The venue was excellent: a former Benedictine monastery in Upper Bavaria .

Projects in the Molecular/Cancer Biology Laboratory

Fri, 31 Dec 1999 00:00:00 +0000

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The Alphabet of Angiogenesis

Tue, 01 Jun 1999 00:00:00 +0000

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The Alphabet of Angiogenesis

Thu, 31 Dec 1998 00:00:00 +0000

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