
Samantha Butler, Ph.D.
Bio
Samantha Butler, Ph.D., studies how the nervous system — the complex network made up of the brain, spinal cord and nerves that run through the body — connects and grows during fetal development. The extraordinarily diverse functions of the nervous system include voluntary and involuntary movement, memory and decision-making and processing information from the five senses. Butler’s work primarily focuses on understanding the mechanisms that establish neural circuitry in the spinal cord to regenerate the nerves that let us sense the environment. These vital functions, such as pain and touch, can be lost due to injuries that sever nerves or cause paralysis as well as diseases that damage nerves such as diabetic neuropathy. Although progress has been made in developing treatments to improve motor function for patients with nerve damage, the same cannot be said for treatments to reestablish sensory abilities, such as those that enable an individual to feel comforted by a reassuring squeeze from a loved one or flinch away from a hot surface to avoid being burned. By pursuing greater understanding of how the nervous system develops, Butler hopes to identify methods that use stem cells or drugs to replicate normal development and regenerate damaged or diseased nerves and nerve connections.
Butler’s work overturned a long-standing paradigm about how axons — thread-like projections that connect cells in the nervous system — grow during embryonic development. Contrary to long-held understanding, Butler discovered that neural progenitors, tissue-specific stem cells that can create any cell type in the nervous system, organize axon growth by producing a pathway of a protein called netrin1 that leads them through their local environment. This insight into axon growth could enable scientists to use netrin1 to regenerate axons in patients with serious nerve damage, such as veterans with combat injuries. Without intervention, these patients face lengthy and painful recovery times, and can lose both movement and sensation in the injured limb due to the gradual loss of nerve cells after injury. Butler hopes to identify ways in which netrin1 can be used to stimulate the rapid regrowth of peripheral nerves, resulting in faster recovery times for patients with nerve damage.
Butler also seeks to identify the ways in which stem cells can be used to repair damaged or abnormal sensory neurons, which are responsible for sense of touch and the ability to feel pleasure and pain. Sensory neurons can be damaged by physical trauma or injury, chemotherapy, autism, aging or other diseases. By identifying how stem cells become spinal sensory neurons during fetal development, Butler has been able to reproduce this process and define methods for making different classes of sensory spinal neurons from stem cells. In her most recent work, Butler has found that these stem cell-derived neurons mirror their naturally occurring counterparts in the embryo to a remarkable extent — setting the stage to use these lab-created sensory neurons for effective cellular therapies that restore sensory function to injured patients.
Butler earned a doctorate in molecular biology from Princeton University and completed a postdoctoral fellowship at Columbia University.
Publications
- In vitro atlas of dorsal spinal interneurons reveals Wnt signaling as a critical regulator of progenitor expansionPublished in Cell Reports on Tuesday, July 19, 2022
- The confidence to questionPublished in Science (Working Life Column) on Thursday, October 7, 2021
- Derivation of dorsal spinal sensory interneurons from human pluripotent stem cellsPublished in STAR Protocols on Friday, March 19, 2021
- Getting in touch with your senses: Mechanisms specifying sensory interneurons in the dorsal spinal cordPublished in Wiley Interdisciplinary Reviews on Thursday, February 25, 2021
- Dorsal commissural axon guidance in the developing spinal cordPublished in Current Topics in Developmental Biology on Thursday, November 19, 2020
- Apcdd1 is a dual BMP/Wnt inhibitor in the developing nervous system and skinPublished in Developmental Biology on Sunday, April 19, 2020
- The Cofilin/Limk1 Pathway Controls the Growth Rate of Both Developing and Regenerating Motor AxonsPublished in The Journal of Neuroscience on Wednesday, November 20, 2019
- Commissural axon guidance in the developing spinal cord: from Cajal to the present dayPublished in Neural Development on Thursday, September 12, 2019
- Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem CellsPublished in Stem Cell Reports on Thursday, January 11, 2018
- Netrin1 establishes multiple boundaries for axon growth in the developing spinal cordPublished in Developmental Biology on Sunday, October 1, 2017
- BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activitiesPublished in eLife on Tuesday, September 19, 2017
- Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal CordPublished in Neuron on Thursday, April 20, 2017
- From classical to current: analyzing peripheral nervous system and spinal cord lineage and fate Published in Developmental Biology on Sunday, February 15, 2015
- Neuronal Organization: Unsticking the Cadherin CodePublished in Current Biology on Monday, December 1, 2014
- Smad1 and 5 but Not Smad8 Establish Stem Cell Quiescence Which Is Critical to Transform the Premature Hair Follicle During Morphogenesis Toward the Postnatal StatePublished in Stem Cells on Tuesday, September 10, 2013
Honors & Affiliations
Honors
- Ablon Scholar, 2019
- Eleanor I. Leslie Term Chair in Pioneering Brain Research, 2018
- Rose Hills Foundation Scholar, 2017
- Stein/Oppenheimer Endowment Award, Gerald Oppenheimer Foundation, 2014
- Spinal Cord Research Foundation/Paralyzed Veterans of America Fellowship, 2000 - 2002
Affiliations
- Member, Neurodifferentiation, Plasticity, Regeneration and Rhythmicity study section, National Institutes of Health, 2022 - 2027
- Reviewer, NIH/NICHD Intellectual and Developmental Disabilities Research Centers, 2020
- Reviewer, Neurodevelopment, Synaptic Plasticity, and Neurodegeneration fellowship study section, National Institutes of Health, 2016 - 2019
- Reviewer, National Institute of Neurological Disorders and Stroke Research Program Award initiative, National Institutes of Health, 2016
- Editorial Board, Developmental Biology, 2014
- Editorial Board, Physiological Genomics, 2014
- Society for Neuroscience
- International Society for Stem Cell Research
- Society for Developmental Biology
Funding
Butler’s work is funded by the National Institutes of Health, the United States Department of Defense, the Merkin Foundation and the UCLA Broad Stem Cell Research Center, including support from The Rose Hills Foundation Innovator Grant and the Wendy Ablon Trust.