This article is part of a series of Cure SMA grant announcements being shared throughout the winter/spring.

Cure SMA has awarded a $150,000 grant to Emily Welby, Ph.D., of the Medical College of Wisconsin for her project titled, ” The role of astrocytes in SMA motor neuron synapse defects.” Dr. Welby is a post-doctoral researcher working in the laboratory of Dr. Allison Ebert.

Dr. Welby is one of three 2020 recipients of the Audrey Lewis Young Investigator Award, periodically given to younger researchers working in the SMA field. Audrey Lewis founded Families of SMA, now Cure SMA, and the goal of this legacy award is to make a positive impact on the early phase of a talented researcher’s career, enabling them to focus on the SMA field and efforts to develop a treatment and cure for SMA.

Dr. Welby and the Ebert lab have previously demonstrated astrocyte dysfunction in both SMA mouse models and patient induced pluripotent stem cell (iPSC)-derived culture systems. Astrocytes, a type of cell in the central nervous system, are critical for supporting the health of motor neurons. Hence, it is possible that dysfunctional astrocytes may play a role in some of the motor neuron defects observed in SMA.

In this project, Dr. Welby will investigate abnormalities in the molecules expressed at the surface of astrocytes generated from SMA-patient derived stem cells. These molecules are known to be important in the formation of synapses (connections between cells) that are critical for astrocyte-neuron communication. Understanding these abnormalities and how they affect synapse formation will give novel insights into motor neuron vulnerability in SMA and may lead to the identification of potential novel therapeutic targets.

Meet Dr. Welby

Tell us about your work?

I am originally from the U.K. and I moved to the United States after completing my Ph.D. in stem cell and regenerative medicine at the Institute of Child Health, University College London. For my doctoral research, I characterized the genetic profile of stem cell-derived photoreceptors and developed a method to isolate these cells for future use in transplantation therapies to treat childhood blindness.

How did you first become involved with SMA research?

I first became involved in SMA research through my postdoctoral training in Dr. Ebert’s lab at the Medical College of Wisconsin. I am passionate about investigating which biological processes go wrong in childhood neurodegenerative disorders, so we can develop therapies to prevent and correct these affected processes. Amazing research has been accomplished towards achieving this goal for SMA patients and continuing to use advancing stem cell technologies will allow us to learn even more about SMA patient-specific changes.

What is your current role in SMA research?

In the Ebert lab, we use stem cell-derived astrocyte and motor neuron cultures as a model system to understand disease mechanisms of neurodegenerative diseases, including SMA. We have previously shown that astrocytes, the supporting cells of the nervous system, are dysfunctional and can contribute towards motor neuron cell death in SMA. We are now investigating how this happens and if we can help the motor neurons survive longer by improving the health of the astrocytes.

What do you hope to learn from this research project?

We think that the supportive role of astrocytes in ensuring proper formation and activity of neuronal synapses, the part of the neuron important for transmitting electrical signals to other cell types, might be impaired in SMA. We hope to learn more about what is causing this impairment.

How will this project work?

Our initial data suggests that astrocytes in SMA may have abnormalities in the molecules they express at the cell surface, which are needed in astrocyte-neuron communication to form proper connections between the cells (synapses). To assess if this is true, we will characterize the cell surface proteins expressed by astrocytes generated from SMA patient-derived stem cells and study these proteins within our astrocyte-motor neuron culture system, to see if they affect synapse formation.

What is the significance of your study?

The proposed study has the potential to significantly impact the understanding of astrocyte-mediated motor neuron loss and lead to the identification of novel targets to that could help restore motor neuron synapse health in SMA.

About Cure SMA’s Basic Research Funding

This grant to Dr. Welby is part of $1,100,000 in new basic research funding that we’re currently announcing. Basic research is the first step in our comprehensive research model. We fund basic research to investigate the biology and cause of SMA, in order to identify the most effective strategies for drug discovery. We also use this funding to develop tools that facilitate SMA research.