Dr. Amanda Mahnke is a researcher and key member of the Collaborative Initiative on FASD (CIFASD). Much of Dr. Mahnke’s research involves the impacts of prenatal alcohol exposure (PAE) on the aging process and healthy aging.
Please watch the short video below, in which Dr. Mahnke summarizes her research in plain language.
FASD United recently had the opportunity to interview Dr. Mahnke about her FASD research and the impact of CIFASD on her work.
FASD United: What has your research with stem cells shown about aging in people with FASD?
Dr. Amanda Mahnke: We have looked at neural stem cells in animal models, that’s the stem cells that form almost all of the cells of the brain. We see time and time again that when there is alcohol exposure, those cells are impacted. These are hearty cells, they want to survive. In order to survive the first thing they do when they react to alcohol exposure is to basically say, “We’ve got to get our other cells made.” By making other cells, these stem cells lose the capacity to make more of themselves, which could impact their ability to repair tissues across the lifespan. My lab is investigating the long-term impacts of alcohol on stem cells, including these neural stem cells.
FASD United: What would you like families and people in the FASD community to most know about your research?
Dr. Amanda Mahnke: I want the community and individuals with FASDs to know that the direction of my research is fundamentally determined by people self- advocating. When individuals with FASD come to me and tell me “We’re not aging healthfully” that drives our research questions and makes us want to discover answers as to why this is occurring and ways to help.
I want the community to know that we are listening and we really do want to improve their health. CIFASD as a whole is working to support people with FASDs, including trying to understand how they age and improve health and healthy aging.
FASD United: Is there a time when something struck you as an “aha moment” as you are doing this research?
Dr. Amanda Mahnke: Yes, two things really hit me hard and shaped my research. One is an amazing self-report study that was done by adults with FASDs. They quantified what aging looks like for individuals with FASDs and clearly showed that aging for people with FASDs is different than what is seen in the general population. Their survey clearly laid out where we should put our efforts as researchers.
The second one was meeting Carl Young, an adult FASD self-advocate, who said to me, “I’m 50 years old and my body’s failing me.” Carl said that to me after I just gave a talk on some of my research. If hearing that doesn’t make you want to get back into the lab and work harder at figuring out what’s going on, nothing else would. That was such an amazing moment of self- advocacy at work.
FASD United: I see that you are researching using microRNAs, which is a fascinating emerging field of research. What have you found there relating to FASD?
Dr. Amanda Mahnke: I am very interested in biomarkers of health risks for individuals with FASDs and our biomarker of choice is something called microRNAs. These are little tiny RNAs that don’t code for a protein, but they act to regulate all of those things that make proteins. Their expression in blood plasma gives us a snapshot of how cells and tissues are adapting and changing following prenatal alcohol exposure.
We are working with other CIFASD researchers, including Tina Chambers and Rajesh Miranda, to see how microRNAs indicate future health risks. We have a paper that’s been submitted that is looking at microRNAs in children and we find that in early childhood these microRNAs are actually able to indicate prenatal alcohol exposure-associated neurodevelopmental delay, as compared to other sources of neurodevelopmental delay. We also uncovered the signature where microRNAs are changing things like collagen and extracellular matrix, and as a basic scientist, I was surprised by that. These data are leading us to ask questions about PAE’s impacts on collagen, which could directly affect things like joint health.
FASD United: Can you talk about your research on machine learning and how this is helping with identification?
Dr. Amanda Mahnke: My lab will often work with big data sets with gigabytes upon gigabytes of data. We have to think of how we make sense of this data, and one of the most fun things over my career in the last 5 to 10 years has been looking at ways to use computing power to help us identify the key critical parts of these data. Machine learning is incredibly helpful because the goal is to take a huge data set and figure out the critical parts that can indicate outcomes. Because of how large the data is, we may never make these connections without machine learning and similar “data reduction” methods to make things manageable. We have currently been using machine learning to identify biology changed by exposure for children and across maternal-child dyads, which is the pair of the mom and child.
In my lab, we are very lucky that we are able to work with collaborators, including CIFASD researcher Dr. Claire Coles, to look at something called DNA methylation, which is a way to mark DNA to change how genes get expressed. We are excited about what we’re seeing in this data, and it’s great having collaborators in the field like Dr. Alexandre A. Lussier who has conducted methylation studies in children and is now helping us figure out what the methylation signatures look like in adults. We are very lucky as researchers to being in such a supportive and collaborative research field.
FASD United: How do you see your research being put into practice and used by families in a tangible way?
Dr. Amanda Mahnke: In my wildest dreams, we will identify how stem cells are changed by prenatal alcohol exposure and be able to leverage a whole library of FDA-approved drugs that are currently being researched by the National Institute on Aging to help with healthy aging. There are drugs that already exist and are in use for other conditions, so we can start with a leg up on knowing how the drugs work and what parts of the body they typically impact. In the general population, using these drugs could support healthy aging for older individuals, age 60 years old and older, but we know for individuals with FASD they may benefit from interventions earlier, even in their 30s. We are hoping to be able to leverage these existing drugs and use them therapeutically during a window that is most helpful for individuals with FASDs to support healthier lifespans.
FASD United: What is the most valuable impact of CIFASD on you and your work?
Dr. Amanda Mahnke: I can truly say that without CIFASD, we would have a hard time figuring out what prenatal alcohol exposure does to human stem cells. Without my collaborations with CIFASD, the cells that I use to model disease states would be very difficult to obtain.
I am an “Early Career Researcher.” As I became faculty and started my own research lab, I realized I didn’t know what I didn’t know and it was, and sometimes still is, scary to all of a sudden feel like a small kid in a big pool. I’m very lucky that I have a couple of colleagues who are at a similar career stage as me and are absolutely fantastic collaborators, such as Dr. Charlis Raineki and Dr. Tamara Bodnar who are also part of CIFASD. Through work with Tamara Bodnar, we have started to look at how proteins in the blood might indicate if specific organ systems are aging early. For individuals with FASDs, it is likely not that the whole body is breaking down at once but that organ system changes are building one on top of the other. Understanding this pattern of when organs are stressed/having issues can help us understand when and where to intervene. These types of collaborations are some of the best parts of my involvement in CIFASD.
FASD United: What do you feel most excited for as you look down the road at the near-term or long-term impacts of your research?
Dr. Amanda Mahnke: I’m really excited at the potential of microRNA biomarkers to be these panels that can be used in the clinic. They use the same technology as a cheek swab that we all got familiar while testing for COVID-19. The technology is already in the clinics and could help an individual with an FASD who is experiencing issues around aging. Biomarker panels could help us identify that certain individuals need to have closer attention paid to their heart or kidneys or to another organ systems at an earlier time point. We are very excited about the potential of microRNAs to be biomarkers across the lifespan.
We are excited about our stem cell work, but also know that getting to the point where our data informs care will take a while. Yes, we do need interventions to improve health for individuals who have an FASD diagnosis right now. There are overall healthy behaviors that can support stem cells, like good nutrition and exercise. We also are hoping to figure out how to more directly impact stem cells in early life to set up lifelong health. My hope is that we will find ways to increase the health span of individuals with FASDs.
FASD United: Is there anything else you’d like people to know kind of about you or your research with CIFASD?
Dr. Amanda Mahnke: As a basic scientist, I am constantly in awe of my clinical collaborators who do such a great job of working with self- advocates. These reciprocal relationships help the researchers do better research and help self-advocates use the research to advocate for their own health and supports. I think that these types of relationships would also improve basic science and would like to develop and incorporate it into my laboratory. Relationships with self- advocates would help us talk more clearly about our research. understand. More importantly, it would provide feedback from the true experts in the field, the individuals with living experiences, on the potential impact and direction of our work.
Note:
Research reported in this publication was supported by the National Institute On Alcohol Abuse And Alcoholism of the National Institutes of Health under Award Number U01AA030185. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.