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Turning glia into neurons inside the brain: a Ph.D. interview with Jessica Giacomoni

Portrait of Jessica Giacomoni (right) and her Ph.D. thesis cover (left).
Jessica Giacomoni (right) defends her Ph.D. thesis 14 October 2022.

On 14 October 2022, Jessica Giacomoni will defend her Ph.D. thesis. With the ultimate goal to develop a possible, future alternative to cell transplantation for the treatment of neurodegenerative disorders, her research efforts have focused on the direct conversion of human glial cells into therapeutic neurons directly within the brain.

Here, she tells us about future possibilities with this emerging therapeutic approach and her experience as a Ph.D student.

What have your Ph.D. studies focused on?

“The pioneering work conducted here in Lund in the 80´s using fetal dopamine neurons for transplantation in Parkinson´s disease has been fascinating and provides support for the concept of restoring dopamine release to improve patient’s motor symptoms. Current efforts now focus on bringing neurons derived from pluripotent stem cells to the clinic, using a protocol that has been developed by the research group where I performed my thesis work. However, exogenous sources for cell transplantation have the limitation of requiring initial immunosuppressive treatments that could lead to other medical risks. Moving forward, restorative brain therapies could be performed using endogenous cell sources.

Therefore, my project has been to explore the direct conversion of human glial cells into neurons which, if performed inside the living brain, leads to an in vivo neuronal replacement, as an alternative to cell transplantation. This can be achieved by targeting existing glial cells and reprogramming them directly into specific neurons by viral vector-mediated gene transfer, without passing through an intermediate pluripotent stage.

My contribution has been to establish cell culture models to study the direct reprogramming of human glial cells into functional neurons and how to improve the targeting of specific glial cells for future direct conversion applications inside the living brain. In my project, I have identified the optimal factor combinations to generate both dopaminergic neurons and GABAergic interneurons and assessed their molecular and electrophysiological properties. I have also used brain slice cultures to demonstrate that selective infection of human glia transplanted in the rodent brain can be achieved by engineering the capsid surface of adeno-associated viruses. In the future, there may not be the need to open up the brain, if specifically designed viral vectors of serotypes able to cross the blood-brain barrier can be administered systemically through a regular intravenous injection. Our next goal is to prove conversion inside the brain and restore motor function in a pre-clinical humanized-xenograft rat model of Parkinson´s disease,” explained Jessica.  

Can you tell us more about the cover of your thesis?

“I have used an MRI scan of my own brain as a basis, taken with the 7 Tesla Facility at Lund University. Then, I added some artistically modified microscope pictures of the glial cells and converted neurons that I worked with, representing the direct conversion process inside the brain. Altogether, it looks like a contemporary-pop art cover, I think,” noted Jessica.

How did you end up doing a Ph.D. at Lund Stem Cell Center?

“I was already working with adult stem cells as a master student in Italy when I became curious about the application of pluripotent stem cells for regenerative medicine. This curiosity brought me to Sweden and I joined Malin Parmar’s group for three months during the summer of 2017. I liked the research team from the beginning, but there was no available position at that time. Later, I returned for a six-month human biology scholarship, whereafter Malin offered me my Ph.D. project,” stated Jessica.

What have you found the most enjoyable during your Ph.D. studies?

“Every small discovery is a reward in itself. In addition, being part of the Developmental and Regenerative Neurobiology research group has allowed me to see the bigger picture of what I am doing. My project is about pre-clinical work, but our research team is involved in the upcoming in-human stem cell clinical trial (STEM-PD) and active in industry collaborations. That process has been exciting to follow from the inside of our group. Getting in touch with patients and meeting the people in need of what I have been working with is motivating. 

I also enjoyed being part of both the Lund Stem Cell Center and MultiPark. Both offer great working environments with amazing infrastructures to carry out research. It is an ideal place for a researcher, as there are plenty of opportunities for social interactions and professional development. For example, during my time as a PhD student, the Research School on stem cell biology with its workshops and Professional Development Program, not only allowed me to learn new valuable skills but also form new friendships and important network connections. Not to forget SCC organizing initiatives “UniStem Day” and “Taking science to school” which have been a great way for me to experience teaching and explain my research to the young public,” highlighted Jessica.

What has been the most challenging aspect?

“Well, things do not always go as you plan, which is rather a rule than an exception as a researcher. Sometimes it is hard to embrace failure, although I believe it is an opportunity to reflect upon what went wrong and gain knowledge and strength by not giving up. Still, the pandemic was hard to predict, and it came to many of us with delays in the research processes and slowness as it made it impossible to travel for a while. I am grateful that I could visit at least one international conference in the US before I defend," noted Jessica.

What are your plans following your Ph.D. defense?

“My project is too interesting! I have not been able to wrap all subprojects up before I defend. So, I would like to stay in the lab for a couple of extra months to finish some projects. After that, I will see. I am open both to academia and to other job opportunities when they come. Thanks to the MentLife program, I have gained insights into how to take the leap from academia to industry if I would like,” remarked Jessica.

Any tips or advice for future Ph.D. students?

"To begin with, I think choosing the right subject and the right team is essential. Doing a Ph.D. is a big commitment; being curious about the project facilitates the heaviest periods. Also, having an honest and open communication with your supervisor is key to getting the proper support during these periods of struggle. The whole team and working environment are important to consider before deciding on a Ph.D project.

Then, once you start this journey, take your time to read the literature and do not rush on the experimental design before you have found the unsolved biological questions in your field. Inform yourself about the educational requirements early on, and if you can get your first authorship close to completion before the halftime, it is a great stress reliever. That gives you space to invest the second half of your Ph.D. studies on long-term goals and potentially initiate projects with higher risk. My last piece of advice, do not forget to have fun and enjoy the bumpy ride,” emphasised Jessica.

Contacts:

Portrait of Jessica Giacomoni. Photo.

Jessica Giacomoni

Ph.D. student
Developmental and Regenerative Neurobiology
Email: jessica [dot] giacomoni [at] med [dot] lu [dot] se

Link to Jessica Giacomoni's profile in the LU Research Portal


Portrait of Malin Parmar. Photo: Kennet Ruona.
Malin Parmar. Photo: Kennet Ruona.

Principal Investigator
PhD, Professor
Developmental and Regenerative Neurobiology 
Wallenberg Neuroscience Center
Phone: +46 46 222 06 20
E-mail: Malin [dot] parmar [at] med [dot] lu [dot] setarget="_self"

Profile in Lund University research portal

Ph.D. Defence Details:

Jessica Giacomoni will defend her Ph.D. thesis titled "Exploring Direct Conversion of Human Glia into Therapeutic Neurons" in Segerfalksalen (BMC A10) in Lund on 14th October at 09:00.

The opponent is Professor, Marisa Karow, Erlangen.

The chairman of the dissertation is Professor, Anders Björklund.

To find out more about the event and save the date please visit our calendar.

Read the Ph.D. thesis "Exploring Direct Conversion of Human Glia into Therapeutic Neurons".