Dr. Sally Temple
Scientific Director and Co-Founder Neural Stem Cell Institute
Adjunct Professor University at Albany
Postdoctoral Fellow Columbia University
PhD in Developmental Neurobiology University College London
As an undergraduate in the zoology department at the University of Cambridge, Dr. Sally Temple dabbled in many aspects of biology. But there was one topic that immediately captured her interest: neurodevelopment. At the time, the field was just beginning to understand the effects of morphogens—molecular cues that guide development—and Cambridge scientists were at the forefront of these breakthroughs. Immersed in this atmosphere of discovery, Sally felt sure that she, too, wanted to pursue a career in science. As her professors were pioneering the study of morphogens and the genetic control of development, Sally would go on to be a pioneer in her own right, breaking open the field of neural stem cells. Today, Sally is the Scientific Director of the Neural Stem Cell Institute, which she co-founded with a vision of streamlining the pipeline from basic science to clinical application. Her lab focuses on using stem cell models to inform therapeutic strategies for neurodegenerative disorders of the brain, spinal cord, and retina.
As she was nearing the end of her time at Cambridge, Sally knew that she wanted to continue learning. She was captivated by the idea of designing and carrying out her own independent experiments, so graduate school seemed like the obvious next step. Pursuing a fascination with glial cells, she joined the lab of Dr. Martin Raff at University College London for her PhD. At the time, it was thought that the nervous system did not contain stem cells—cells with the ability to differentiate into a variety of cell types—but might contain precursor cells able to become one cell type or another depending on environmental cues. In the Raff lab, Sally focused on the progenitor cells in the developing optic nerve that become glia. She set out to test whether a single progenitor cell was able to turn into multiple glial subtypes. To answer this question, Sally developed a novel technique called clonal culture which involves plating each progenitor cell in its own well. When these isolated progenitor cells divide and differentiate, the cells later found in each well are known to be from the same lineage—to have come from the same single progenitor. Using this method, she identified a type of progenitor in the optic nerve that gives rise to both astrocytes and oligodendrocytes, two different types of glia. While this discovery was an important one, the methodology itself was also a big advance for the field, inspiring further lineage studies by Sally and others.
Sally then moved to the U.S. to do her postdoctoral work at Columbia University, where she expanded her repertoire of molecular techniques. When her husband decided to go to medical school in Miami, she moved with him, cutting per postdoc short and landing a position as an instructor at the University of Miami. Funded by a grant from the Royal Society, Sally was given the freedom to explore whatever research direction she wanted. She decided to apply the clonal techniques she had used on the optic nerve in a different context: the developing brain. She found some cells in the developing brain that only gave rise to neurons. Others became only glial cells. Surprisingly, though, Sally also found a cell that gave rise to both neurons and glia—the first evidence of a neural stem cell. This discovery broke open a new field within the study of neurodevelopment.
Sally recognized the incredible potential neural stem cells might have for both modeling and treating neural disorders. However, neither the typical academic route nor the classic industry route seemed like the best option for exploring this potential. Sally did not want to give up doing basic science and wanted to maintain the intellectual freedom characteristic of academia. However, she also wanted to be able to bring her discoveries to the clinic with an efficiency more typical in industry. Her husband—a retina specialist and researcher—shared the same dream. So they decided to turn that dream into reality, co-founding a non-profit research institute: the Neural Stem Cell Institute. It comprises several groups doing basic science but with a focus on creating therapeutics for neurodegenerative disease.
At the Neural Stem Cell Institute, Sally leads several projects focused on using stem cells to model neural diseases. By the time that patients begin to experience symptoms of a neurodegenerative disease, there is already significant loss of brain tissue, making it difficult to pinpoint the early molecular mechanisms that cause cell dysfunction and death. Organoids—3D culture systems—allow researchers to take cells from patients with neurodegenerative disorders and observe how the cells’ genetic makeup might lead to its dysfunction. For instance, Sally’s group found that, after 6 months in culture, organoids of cells from patients with frontotemporal dementia show increased glutamatergic neuron death. They can now focus on the period before neural death to understand the precise ways in which these cells become unhealthy. This understanding could lead to new therapeutics for patients genetically at risk for frontotemporal dementia.
While studies such as this one are still in the “discovery phase”, others are further along in the pipeline. Some years ago, working with her husband, Dr. Jeff Stern, Sally’s group discovered a stem cell in the adult human retinal pigment epithelium (RPE), a thin layer of cells in the eye that supports the photosensitive cells in the retina. This stem cell presented a unique potential strategy for treating age-related macular degeneration—a common retinal disorder that can result in loss of high-acuity and color vision—by helping to replace the degenerating RPE. It is possible to take these stem cells from the donated eyes of cadavers and use them to generate billions of healthy RPE cells. These cells can then be injected sub-retinally into patients with macular degeneration. The hope is that the implanted cells will restore RPE support the photosensitive cells, thus rescuing vision loss in patients. To carry out the clinical study, Sally and Jeff co-founded a company: Luxa Biotechnology, LLC. Now with Investigational New Drug allowance from the FDA, the clinical trial is about to start. This is the type of bench-to-bedside trajectory that Sally had envisioned when starting the Neural Stem Cell Institute.
In addition to co-founding an institute and Luxa, Sally also co-founded a reagent company. When she began working with human stem cells, she faced an issue: the cells needed to be fed every day or they would die. What was it in the cell culture media that only lasted a day? To answer this question, Sally separately tested different components of the media, eventually discovering that fibroblast growth factor 2 (FGF2), an important component of the media, had a half-life of only four hours from the time it was added to the cultured cells. Thus not only did the cells need feeding every day, but they were also being exposed to a rollercoaster of FGF2, with high concentrations at feeding that then dropped off precipitously until the next feeding. To combat this issue, Sally created a slow-release version of FGF2 in which the growth factor is encapsulated in a biodegradable microbead. This reduces the need for media changes to twice a week instead of every day and allows for a more continuous FGF2 concentration across time. Realizing that this would help other scientists as it was helping her, Sally co-founded Stem Cultures, LLC to sell slow-release FGF2 and other growth factor innovations. A portion of the profits from the company go directly back into the non-profit research institute. This funding flow is especially useful for driving exploratory pilot experiments and generating data to use when applying for grants.
As she looks back at her career, Sally stresses the importance of following one’s own vision of “success”. For her, that was not a position at a prestigious R1 institution in the middle of a big city. With three kids, Sally knew she wanted to prioritize being in a community that would give her the family-friendly lifestyle she wanted. The Neural Stem Cell Institute is in Albany, New York, a community that has allowed Sally to find this balance of family life and top-notch science. Sally has been an innovator at every turn of her career, from her graduate work creating a clonal culture system, to her discovery of a neural stem cell, to co-founding an institute enabling clinical translation of basic science discovery. In stages of her career when she realized the typical mold was not right for her, she created a new mold. As others in the field chase their own dreams of “success”, whatever that might look like for them, they have no better role model than Sally in how to turn their science dreams into reality.
Listen to Catie’s full interview with Sally on March 11, 2022 below!
