Dr. Amanda Sferruzzi-Perri, the University of Cambridge, United Kingdom
An Interview with the 2020 Hans Sigrist Prize Winner
The Hans Sigrist Foundation sat down with the 2020 Prize Winner, Dr. Amanda Sferruzzi-Perri and the 2020 Hans Sigrist Prize Committee Chair, Prof. Christiane Albrecht.
Hans Sigrist Foundation:
Congratulations on winning the 2020 Hans Sigrist Prize. Were you surprised to find out that you had been selected as the prize winner?
Sferruzzi-Perri:
Yes, I certainly was. In a year that was quite challenging due to the Covid-19 pandemic, hearing that I had won the prize was like a ray of light out of the darkness. I not only feel very honored to be awarded such a prestigious prize, but also really pleased that the Foundation recognized this field of research.
Hans Sigrist Foundation:
We are grateful for Professor Christiane Albrecht's initiative. She responded to our call for proposals from the faculty at the University of Bern and proposed that the prize be awarded in this important and interesting field, Maternal-Fetal Communication. The Foundation can only do what we do thanks to the faculty members who make proposals for the prize field and who lead the committee through a lengthy search process.
If you look back to when you were first trying to decide what to study at the university, what sparked your interest in this particular field?
Sferruzzi-Perri:
I suppose I have always been fascinated by the sciences and by how the human body works. I completed a Bachelor of Science degree at the University of Adelaide, and then I added on an honors year, where I was able to undertake different types of research in two labs. During that honors year, I spoke to a lot of people and did some reading, and I began to learn how common pregnancy complications were, that they affect about one in every five women during pregnancy. I went on to pursue a Ph.D. focused on pregnancy research, and in particular, on the role of hormones in the mother in regulating fetal growth. Through that work, I developed an interest in the placenta, which is the organ that develops during pregnancy to control nutrient and oxygen supply from the mother to the fetus. The placenta performs many other roles too, and it is absolutely fundamental to pregnancy success. If we can understand how the placenta develops and functions, hopefully, we can then fully understand the origins of these life-threatening pregnancy complications, which is now the main focus of my research at the University of Cambridge.
Hans Sigrist Foundation:
Prof. Albrecht, could you tell us a little bit about how you decided to choose this field for the prize, and what Maternal-fetal Communication means, for the lay audience?
Albrecht:
I found it absolutely amazing how processes that occur very early in the pregnancy may have such an enormous effect in adult life and in the life of the offspring. When we understand the functions of the placenta and the consequences of a dysfunction of the placenta on fetal development, then we can prevent problems later in life and even societal problems. What inspired me to propose this field for the Hans Sigrist Prize was to highlight how this research field can have a critical impact on society and on the well-being of people. Think of how devastating it is when a pregnancy is not successful, not only for the parents, but also how it impacts the health care system.
Sferruzzi-Perri:
What we and others are really interested in is what the critical environmental factors are, for example, maternal nutrition. We know that high sugar, high fat diets, or undernutrition, can predispose a woman to develop a pregnancy complication, indicating that environmental factors in the mother must determine how the placenta forms and functions. We also know that factors like high stress levels and certain disease states increase the risk of pregnancy complications. We are really interested in understanding the influence of different environmental conditions in the mother on how the placenta forms and functions, and what that means for fetal growth.
Coming back to Prof. Albrecht's important comment, it is not just about the health of the pregnancy, but about the lifelong health of the mother and the child. We know that if the placenta does not form and function properly, nutrient and oxygen supply to the very sensitive fetus, and to its individual organs, will be altered. That can lead to permanent changes in the way that they function, and in later life, we know that this increases the risk that the child will develop type 2 diabetes, heart disease, or obesity, which are some of the largest killers worldwide. So, if we can understand how the environment of the mother impacts the function and formation of the placenta, which in turn impacts fetal development and lifelong health, we may pave the way for improving lifelong health more broadly.
Hans Sigrist Foundation:
Could scientists and doctors intervene during an individual pregnancy?
Sferruzzi-Perri:
Ideally, if we can understand what determines a healthy pregnancy, we can better inform the behaviors of both already expectant parents and of those who are planning a family, encouraging them to make healthy life choices, to start that a bit earlier. Moreover, if we know what influences the formation and function of the placenta and if we know when defects may occur, there may be a way that we can improve the placental formation and function by targeting an agent or changing the mother's environment in pregnancy. We could then prevent the changes in fetal development that lead to an increased risk of disease in adult life.
Hans Sigrist Foundation:
Can the placenta influence the mother’s cardiovascular and metabolic system?
Sferruzzi-Perri:
Yes, we know that the placenta is not merely a passive receiver of signals, it is also a sender of signals, including hormones that circulate in the mother and possibly also in the fetus to affect various body systems. In fact, in terms of your question about the potential influence of the placenta in regulating the mother, that is actually one key area that we are now moving into very actively in my lab. For example, placental hormones in the mother act at the level of tissues like the pancreas, to influence insulin production, and act at the level of the cardiovascular system, to promote blood flow distribution to the uterus to support oxygen and nutrient transfer to the fetus. The placenta is an absolutely remarkable organ. It has to form, to function, and to serve two individuals, the mother and the fetus, at the same time.
Hans Sigrist Foundation:
How does this start?
Sferruzzi-Perri:
As Prof. Albrecht highlighted, these processes are happening very early in development, at the level of the uterus, to allow the fetus to implant into the mother, to tap into the nutrient supply, and even preparing her, not just in terms of changing her organ systems, but also her behavior, so that she can prepare for lactation and support the baby after the pregnancy. The legacy of this communication of the placenta to the mother goes beyond just pregnancy itself. It goes even later into the life of the child and also the mother.
If a baby is exposed to a poor gestational environment, for example if a mother develops a complication like gestational diabetes, where the mother cannot control her glucose levels, or if the mother develops preeclampsia, which is life-threatening high blood pressure during pregnancy, this is often due to failed communication of the placenta with the mother. These women are much more likely to develop Type 2 diabetes and heart disease in later motherhood. However, what we do not know is the extent to which pregnancy is a stress test, exposing a genetic vulnerability in the mother, or whether it is something about the placenta and the way that it is communicating to the organs of the mother, that may induce a permanent change that impacts the function of different systems of the mother that make her, therefore, more susceptible to disease in the years and decades after a pregnancy. So, in my lab, we are actively trying to understand the extent to which the placenta may be communicating to the mother. We are doing this by using models where we can alter the way in which the placenta secretes hormones into the mother. We are also trying to survey the complete repertoire of hormones that are released from the placenta, to see what effect they have on different organs of the mother and to see also whether they could be biomarkers of pregnancy health. As one can imagine, pregnancy is a really challenging physiological process to study, especially in humans, because of ethical challenges and considerations in conducting studies with women and children. Also, a placenta is only available for research after the delivery, so it is really challenging to understand the processes that may lead up to a pregnancy complication. So, if we can improve methods to survey the way in which the placenta is functioning in the pregnancy, say through circulating hormones that the placenta produces, then maybe that could provide an indicator of how the placenta is functioning and forming. At the moment, the pregnancy test is based on the placental hormone HCG, so we know that there are possibilities there. We just do not know all the repertoire of different hormones secreted. In addition, it may not just be about hormones, as there are other less traditional signaling molecules that others in the field are working on like metabolites, shed RNA and DNA, and exosomes that are also thought to communicate from the placenta to the mother. It is indeed a very exciting field!
Hans Sigrist Foundation:
Do you study and follow women and children or do you work with animal studies?
Sferruzzi-Perri:
Human studies are very challenging to do, because pregnancy and life span in humans are long. Also, actually, quite a big part of the field is focused on observational or association studies in humans. People like Prof. Albrecht have really paved the way for associations of pregnancy health and the subsequent health of the child. However, the data for humans is relatively limited, due to the challenges in collecting information that may take 50 years. So, my lab, among others, employs animal models, where pregnancy and lifespan are much shorter, allowing us to get a greater amount of information, not just in a shorter time frame, but also to tell us about the timing of specific processes that are involved.
In my lab, for example, we use mice as a model, because we can environmentally challenge the pregnancies. There are techniques that can alter certain genes within certain compartments in the pregnancy, like the placenta, the fetus, or the mother. Then, we can follow up on the health of the mother and the child, in the months after the delivery. We have traditionally looked at offspring into adult life, but we have started to look at whether those offspring may themselves also be programmed to have complications in their pregnancy, because of an exposure to a suboptimal environment in their early development.
Albrecht:
The placenta is still a very under-investigated organ, although it has this incredible importance throughout life, not only throughout pregnancy actually. There are so many open questions, and it is still such a fascinating area of research. I just hope that dedicating the prize field and prize funds to it will increase its exposure and motivate others to join this field and to investigate further all the important processes going on throughout pregnancy, which are being linked to the placenta.
Hans Sigrist Foundation:
Speaking of the prize funds, are there types of research that you want to do that are difficult to find funding for, with which the prize money may help you?
Sferruzzi-Perri:
I think, comparatively, as Prof. Albrecht touched upon, research on the placenta and pregnancy is quite a neglected area compared to other fields that seem to be much more appealing to funding agencies, like cancer and even cardiovascular diseases and diabetes. Yet, there are so many links, especially in the cardiometabolic field, with origins that relate to the very early life exposure of an individual. By being able to attain preliminary data to make applications even stronger and more competitive, we may have a better chance of being funded. This is important especially when going up against other fields of research that tend to be focused more on treatment rather than on prevention. If people think about prevention, then they should really be thinking about the placenta and about early life exposures. This award will certainly allow us to raise greater awareness to funding agencies, demonstrating that this is an important area of research.
Hans Sigrist Foundation:
Do you foresee collaborating with Prof. Albrecht?
Sferruzzi-Perri:
Before being awarded the prize, I knew Prof. Albrecht mostly from her publication record, because she does fantastic work on the placenta and nutrient handling, in the context of fetal outcomes.
I am really grateful that the foundation would allow opportunities for me to come and to interact with people at the University of Bern, and to help to design projects to accommodate exchanges between my lab and others in Bern, so that we can maximize individual research programs. Also, to do really impactful projects, it requires a team effort. Samples, for example, that women donate, or even our animal samples, they are so precious. We cannot be experts on everything, and we are pleased to work on samples that others have collected, to maximize the outputs. Similarly, we are happy to provide samples to others to help build knowledge for the field.
Hans Sigrist Foundation:
You mentioned associational studies. Can you explain what associational studies are, in your field, for the lay person?
Sferruzzi-Perri:
We can only really get access to the placenta at the end of pregnancy. What this means is that we are looking at it at the end of a process and trying to understand how the pregnancy ended up that way, whether healthy or pathological. Prof. Albrecht does fantastic work in isolating the specialized cells, the trophoblasts, and from looking at how they behave in culture, she works to develop an understanding of why the baby or the pregnancy may not have had the healthiest of outcomes.
Albrecht:
For example, what we do, we isolate these important cells that form the barrier between the mother and the fetus in the placenta, and we look at what happens if this barrier is disturbed. Can this lead to specific phenotypes that we then see, either in the fetus or in the mother? So, we examine what has been disturbed - is it the nutrient exchange or is it the signaling? Are the very important hormones not being produced anymore? These are the kind of questions that we try to sort out - the phenotype that we see, so that we can reproduce it or nail it down to some effects on a cellular level.
Hans Sigrist Foundation:
Are you working with human samples that are donated?
Albrecht: Dr. Sferruzzi-Perri and I have complementary approaches. In my lab in Bern, we are mostly working on human cells, isolating these, and Dr. Sferruzzi-Perri, in Cambridge, has created these wonderful mouse models.
So, we have very complimentary approaches, which would allow us to design projects together. With Dr. Sferruzzi-Perri’s research, we can also look at fetal development, which we cannot do in humans, for ethical reasons.
Sferruzzi-Perri:
By expanding and learning from others, you have so much more capacity and more information that pushes the field further.
Hans Sigrist Foundation:
On the topic of future development, I have asked every prize winner for the past several years, what advice they have for someone who is just starting university and who is interested in this field. What would you suggest?
Sferruzzi-Perri:
My interest in this specific field came from really amazing conversations with others. When you are young, you feel nervous to go up and speak to people whom you do not know, but if you are drawn towards a certain field, use that as your motivation to go speak to people, to go speak to the lecturers who are teaching those courses, to see whether there are opportunities, for example, to go and volunteer in a lab. People are usually happy to share knowledge, advice, and expertise. When I was quite young, I had the opportunity to work in a hospital lab over the summer for six weeks. I was amazed by being able to see this work first hand, in a culture dish, for the first time. I think I did not have a feeling for what scientific research meant until I was physically in the lab.
Albrecht:
I agree. When I was a Ph.D. student, it was a bit intimidating to approach these already very successful researchers. Just approach them, they like to share what they do.
Sferruzzi-Perri:
Yes, people do not necessarily give out advice and information unless one seeks it, so it is important to be quite active about it. Knowing which paths are available is really helpful. It does not matter which career stage one is at; we all have an opportunity to learn from one another. Indeed, I feel I am learning all the time from those around me.