{{Short description|American academic}} {{Infobox scientist | name = Samantha Butler | image = File:Samantha Butler Wikipedia Headshot.jpg | fields = Developmental Biology, Neuroscience, Stem Cell Biology | workplaces = University of California, Los Angeles | alma_mater = University of Cambridge, Princeton | doctoral_advisor = Yasushi Hiromi | academic_advisors = Jane Dodd | known_for = Understanding the mechanisms that establish and regenerate the spinal cord | website = {{URL|https://butlerlab.neurobio.ucla.edu/}} }} '''Samantha J. Butler''' is a British American developmental neuroscientist at University of California, Los Angeles. She studies how the sensory interneurons in the spinal cord are first established during development and then connect to form circuits.<ref>{{Cite web |date=2024-11-14 |title=Homepage {{!}} Butler Research Lab |url=https://butlerlab.neurobio.ucla.edu |access-date=2025-05-22 |website=butlerlab.neurobio.ucla.edu |language=en}}</ref> Her research goal is to develop drugs and stem cell-based therapies that help people with spinal cord injuries and nerve damage regain sensation.
== Early life and education == Butler grew up in Oxford, England, and is the granddaughter of astrophysicist, Fred Hoyle.<ref name="SNP">{{Cite journal |date=December 3, 2013 |title=Working to grow new wiring |url= |journal=Science News Prime |volume=2 |issue=45 |pages= |doi= |issn=}}</ref> She attended Headington Rye Oxford, where she was taught mathematics by Lily Atiyah, the wife of Michael Atiyah, also a mathematician. After graduating, she spent her gap year first taking mathematics modules at Oxford Brookes University and then working at the Tata Institute of Fundamental Research, Mumbai, India.{{citation needed|date=May 2025}}
While reading Natural Sciences as an undergraduate at the University of Cambridge, Butler became interested in developmental genetics. She completed a Part II in Genetics (1990), studying mutations in the ''ultrabithorax'' gene, part of the Hox complex in ''Drosophila melanogaster'', with Michael Akam.{{citation needed|date=May 2025}} In 1996, she received her Ph.D. in Molecular Biology from Princeton University, advised by Yasushi Hiromi. Her doctoral studies in developmental genetics, focused on charactering an enhancer trap line (h214), that was a candidate for encoding specific neural identity in the developing ''Drosophila'' eye.<ref>{{Cite web |title=Molecular and genetic characterisation ofh214: A gene expressed in the R7 photoreceptor cell throughout the development of the compound eye in Drosophila melanogaster - ProQuest |url=https://www.proquest.com/docview/304260401 |access-date=2025-05-22 |website=www.proquest.com |id={{ProQuest|304260401}} |language=en}}</ref> The associated gene was found to be a cell adhesion molecule and was thus called "klingon."<ref>{{Cite journal |last1=Butler |first1=Samantha J. |last2=Ray |first2=Sandip |last3=Hiromi |first3=Yasushi |date=1997-02-15 |title=klingon, a novel member of the Drosophila immunoglobulin superfamily, is required for the development of the R7 photoreceptor neuron |url=https://journals.biologists.com/dev/article-abstract/124/4/781/39592/klingon-a-novel-member-of-the-Drosophila?redirectedFrom=fulltext |journal=Development |volume=124 |issue=4 |pages=781–792 |doi=10.1242/dev.124.4.781 |pmid=9043060 |issn=0950-1991|url-access=subscription }}</ref>
From 1997 to 2003, Butler worked as a postdoctoral fellow with Jane Dodd at Columbia University, in the Department of Physiology and Cellular Biophysics. At around this time, inspired by a heartfelt plea by a paraplegic man at a conference,<ref name="SNP" /> Butler switched model systems to work on axon guidance mechanisms in the developing vertebrate spinal cord. Her studies showed that the roof plate secretes a diffusible repellent that orients commissural axons away from the dorsal midline.<ref>{{Cite journal |last1=Augsburger |first1=Adela |last2=Schuchardt |first2=Anita |last3=Hoskins |first3=Sally |last4=Dodd |first4=Jane |last5=Butler |first5=Samantha |date=1999-09-01 |title=BMPs as Mediators of Roof Plate Repulsion of Commissural Neurons |url=https://www.sciencedirect.com/science/article/pii/S0896627300808272 |journal=Neuron |volume=24 |issue=1 |pages=127–141 |doi=10.1016/S0896-6273(00)80827-2 |pmid=10677032 |issn=0896-6273|doi-access=free }}</ref> Butler further demonstrated that this repellent is mediated by the bone morphogenic protein (BMP) growth family, the first studies to demonstrate that growth factors could act as axon guidance signals.<ref>{{Cite journal |last1=Butler |first1=Samantha J. |last2=Dodd |first2=Jane |date=2003-05-08 |title=A Role for BMP Heterodimers in Roof Plate-Mediated Repulsion of Commissural Axons |url=https://www.sciencedirect.com/science/article/pii/S089662730300254X |journal=Neuron |volume=38 |issue=3 |pages=389–401 |doi=10.1016/S0896-6273(03)00254-X |pmid=12741987 |issn=0896-6273|doi-access=free }}</ref> Together, these findings suggested that the same signal can reiteratively specify different cellular processes for neurons at different stages of their development. During this time, Butler was funded by a fellowship from the Paralyzed Veterans of America.
== Research == From 2004 to 2013, Butler was an assistant professor in the Biological Sciences department at the University of Southern California. In 2013, Butler moved to the David Geffen School of Medicine at the University of California, Los Angeles where she is a professor in the Department of Neurobiology and the Vice Chair for Community. She has held the Eleanor I. Leslie Chair in Pioneering Brain Research.<ref name=":0">{{Cite web |title=The Eleanor I. Leslie Term Chair in Pioneering Brain Research – UCLA Brain Research Institute (BRI) |url=https://bri.ucla.edu/grants-and-fellowships/eleanor-i-leslie-term-chair-in-pioneering-brain-research/ |access-date=2025-05-22 |language=en-US}}</ref>
Butler's research focus is to understand the mechanisms that establish and regenerate neural circuitry. She has identified the signaling pathways that permit BMPs to direct cell fate and axon guidance decisions, two strikingly different processes in the generation of neural circuits.<ref>{{Cite journal |last1=Yamauchi |first1=Ken |last2=Phan |first2=Keith D. |last3=Butler |first3=Samantha J. |date=2008-03-15 |title=BMP type I receptor complexes have distinct activities mediating cell fate and axon guidance decisions |url=https://journals.biologists.com/dev/article-abstract/135/6/1119/65056/BMP-type-I-receptor-complexes-have-distinct?redirectedFrom=fulltext |journal=Development |volume=135 |issue=6 |pages=1119–1128 |doi=10.1242/dev.012989 |pmid=18272594 |issn=0950-1991|url-access=subscription }}</ref> She then showed that BMPs do not act as morphogens to pattern the dorsal spinal cord. Rather, different BMP ligands promote progenitor patterning and/or neuronal differentiation to direct a unique range of dorsal cellular identities.<ref name=":1">{{Cite journal |last1=Andrews |first1=Madeline G |last2=del Castillo |first2=Lorenzo M |last3=Ochoa-Bolton |first3=Eliana |last4=Yamauchi |first4=Ken |last5=Smogorzewski |first5=Jan |last6=Butler |first6=Samantha J |date=2017-09-19 |editor-last=Bronner |editor-first=Marianne |title=BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities |journal=eLife |volume=6 |article-number=e30647 |doi=10.7554/eLife.30647 |doi-access=free |pmid=28925352 |pmc=5605194 |issn=2050-084X}}</ref>
By dissecting the developmental mechanisms by which BMPs direct cell fates, Butler has established the first directed differentiation protocols that generate spinal sensory interneurons from mouse<ref name=":1" /> and human<ref>{{Cite journal |last1=Gupta |first1=Sandeep |last2=Sivalingam |first2=Daniel |last3=Hain |first3=Samantha |last4=Makkar |first4=Christian |last5=Sosa |first5=Enrique |last6=Clark |first6=Amander |last7=Butler |first7=Samantha J. |date=2018-02-13 |title=Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells |journal=Stem Cell Reports |volume=10 |issue=2 |pages=390–405 |doi=10.1016/j.stemcr.2017.12.012 |pmid=29337120 |pmc=5832443 |issn=2213-6711}}</ref><ref>{{Cite journal |last1=Gupta |first1=Sandeep |last2=Yamauchi |first2=Ken |last3=Novitch |first3=Bennett G. |last4=Butler |first4=Samantha J. |date=2021-03-19 |title=Derivation of dorsal spinal sensory interneurons from human pluripotent stem cells |journal=STAR Protocols |volume=2 |issue=1 |article-number=100319 |doi=10.1016/j.xpro.2021.100319 |pmid=33659900 |pmc=7890043 |issn=2666-1667}}</ref> stem cells. These protocols make stem cell''-''derived sensory interneurons that are transcriptionally indistinguishable from their endogenous counterparts,<ref>{{Cite journal |last1=Gupta |first1=Sandeep |last2=Kawaguchi |first2=Riki |last3=Heinrichs |first3=Eric |last4=Gallardo |first4=Salena |last5=Castellanos |first5=Stephanie |last6=Mandric |first6=Igor |last7=Novitch |first7=Bennett G. |last8=Butler |first8=Samantha J. |date=2022-07-19 |title=In vitro atlas of dorsal spinal interneurons reveals Wnt signaling as a critical regulator of progenitor expansion |journal=Cell Reports |volume=40 |issue=3 |article-number=111119 |doi=10.1016/j.celrep.2022.111119 |pmid=35858555 |pmc=9414195 |issn=2211-1247}}</ref> and will facilitate developing cellular replacement therapies to reestablish sensory connections in injured patients.<ref>{{Cite web |title=UCLA researchers find a way to repair nerve damage with stem cells |url=https://dailybruin.com/2018/02/05/ucla-researchers-find-a-way-to-repair-nerve-damage-with-stem-cells |access-date=2025-05-22 |website=Daily Bruin}}</ref><ref>{{Cite web |last=Ring |first=Karen |date=2018-01-11 |title=UCLA scientists make sensory nerves from human stem cells for the first time |url=https://blog.cirm.ca.gov/2018/01/11/ucla-scientists-make-sensory-nerves-from-human-stem-cells-for-the-first-time/ |access-date=2025-05-22 |website=The Stem Cellar |language=en}}</ref>
Butler has also identified a critical mechanism that controls the rate of axon outgrowth during embryogenesis and axon regeneration.<ref>{{Cite journal |last1=Phan |first1=Keith D. |last2=Hazen |first2=Virginia M. |last3=Frendo |first3=Michele |last4=Jia |first4=Zhengping |last5=Butler |first5=Samantha J. |date=2010-11-17 |title=The Bone Morphogenetic Protein Roof Plate Chemorepellent Regulates the Rate of Commissural Axonal Growth |url=https://www.jneurosci.org/content/30/46/15430.long |journal=Journal of Neuroscience |language=en |volume=30 |issue=46 |pages=15430–15440 |doi=10.1523/JNEUROSCI.4117-10.2010 |issn=0270-6474 |pmid=21084599|pmc=3064494 }}</ref> Manipulating this mechanism permits more rapid functional recovery after a nerve crush,<ref>{{Cite journal |last1=Frendo |first1=Michele E. |last2=Silva |first2=Alexandra da |last3=Phan |first3=Keith D. |last4=Riche |first4=Soizic |last5=Butler |first5=Samantha J. |date=2019-11-20 |title=The Cofilin/Limk1 Pathway Controls the Growth Rate of Both Developing and Regenerating Motor Axons |url=https://www.jneurosci.org/content/39/47/9316 |journal=Journal of Neuroscience |language=en |volume=39 |issue=47 |pages=9316–9327 |doi=10.1523/JNEUROSCI.0648-19.2019 |issn=0270-6474 |pmid=31578231|pmc=6867821 }}</ref> thereby offering the hope of improving recovery times for patients with serious peripheral nerve injuries.<ref>{{Cite web |title=Researchers identify molecular process that could accelerate recovery from nerve injuries |url=https://newsroom.ucla.edu/releases/molecular-process-accelerates-nerve-injury-recovery |access-date=2025-05-22 |website=UCLA |language=en-us}}</ref>
Butler reignited the debate about the mechanism by which netrin1, the first guidance cue identified in vertebrates, functions in the spinal cord.<ref>{{Cite news |title=Study overturns seminal research about the developing nervous system |url=https://newsroom.ucla.edu/releases/study-overturns-seminal-research-about-the-developing-nervous-system |archive-url=https://web.archive.org/web/20250328135841/https://newsroom.ucla.edu/releases/study-overturns-seminal-research-about-the-developing-nervous-system |archive-date=2025-03-28 |access-date=2025-05-22 |work=UCLA |language=en-us |url-status=live }}</ref><ref>{{Cite web |last=Samjbutler |date=2017-05-16 |title=The evolution of an axon guidance model: from chemotaxis to haptotaxis |url=https://thenode.biologists.com/evolution-axon-guidance-model-chemotaxis-haptotaxis/research/ |access-date=2025-05-22 |website=the Node |language=en}}</ref> Her studies have demonstrated that netrin1 promotes axon growth not by long-range chemotaxis, but rather by short-range haptotaxis, the directed growth of cells along an adhesive surface.<ref>{{Cite journal |last1=Varadarajan |first1=Supraja G. |last2=Kong |first2=Jennifer H. |last3=Phan |first3=Keith D. |last4=Kao |first4=Tzu-Jen |last5=Panaitof |first5=S. Carmen |last6=Cardin |first6=Julie |last7=Eltzschig |first7=Holger |last8=Kania |first8=Artur |last9=Novitch |first9=Bennett G. |last10=Butler |first10=Samantha J. |date=2017-05-17 |title=Netrin1 Produced by Neural Progenitors, Not Floor Plate Cells, Is Required for Axon Guidance in the Spinal Cord |journal=Neuron |volume=94 |issue=4 |pages=790–799.e3 |doi=10.1016/j.neuron.2017.03.007 |pmid=28434801 |pmc=5576449 |issn=0896-6273}}</ref><ref>{{Cite journal |last1=Varadarajan |first1=Supraja G. |last2=Butler |first2=Samantha J. |date=2017-10-01 |title=Netrin1 establishes multiple boundaries for axon growth in the developing spinal cord |journal=Developmental Biology |volume=430 |issue=1 |pages=177–187 |doi=10.1016/j.ydbio.2017.08.001 |pmid=28780049 |pmc=5786155 |issn=0012-1606}}</ref> These studies suggest that neural progenitors have an intrinsic capacity to form axon growth tracts, a critical insight for promoting directed, fasciculated regenerative axonal growth. Butler has continued to identify unexpected roles for netrin1,<ref>{{Cite web |title=Scientists discover 'entirely unanticipated' role of protein netrin1 in spinal cord development |url=https://newsroom.ucla.edu/releases/scientists-discover-entirely-unanticipated-role-of-protein-netrin1-in-spinal-cord-development |access-date=2025-05-22 |website=UCLA |language=en-us}}</ref> most recently finding that the polarized distribution of netrin1 in the developing spinal cord also acts as a boundary to restrict BMP signaling and thereby regulate cell fate decisions.<ref>{{Cite journal |last1=Alvarez |first1=Sandy |last2=Gupta |first2=Sandeep |last3=Mercado-Ayon |first3=Yesica |last4=Honeychurch |first4=Kaitlyn |last5=Rodriguez |first5=Cristian |last6=Kawaguchi |first6=Riki |last7=Butler |first7=Samantha J. |date=2024-11-26 |title=Netrin1 patterns the dorsal spinal cord through modulation of Bmp signaling |journal=Cell Reports |volume=43 |issue=11 |article-number=114954 |doi=10.1016/j.celrep.2024.114954 |pmid=39547237 |pmc=11756817 |issn=2211-1247}}</ref>
== Selected honors and awards == * 2000 Spinal Cord Research Foundation/Paralyzed Veterans of America Fellowship * 2017 Rose Hills Foundation Scholar * 2018 Eleanor I. Leslie Chair in Pioneering Brain Research<ref name=":0"/> * 2019 JCCC-BSCRC Ablon Scholar<ref>{{Cite web |date=2023-10-03 |title=2019 Ablon Scholar {{!}} Butler Research Lab |url=https://butlerlab.neurobio.ucla.edu/2019-ablon-scholar |access-date=2025-05-22 |website=butlerlab.neurobio.ucla.edu |language=en}}</ref> * 2022 UCLA Molecular Biology Institute Mentoring Award for faculty<ref>{{Cite web |date=2024-02-15 |title=Professor Samantha Butler Wins Diversity, Equity and Inclusion Award {{!}} Neurobiology Department |url=https://neurobio.ucla.edu/professor-samantha-butler-wins-diversity-equity-and |access-date=2025-05-22 |website=neurobio.ucla.edu |language=en}}</ref> * 2022 Standing member, NDPR study section, NIH<ref>{{Cite web |title=NDPR {{!}} NIH Center for Scientific Review |url=https://public.csr.nih.gov/StudySections/DNDA/BN/NDPR |access-date=2025-05-22 |website=public.csr.nih.gov}}</ref> * 2023 Faculty/Staff Partnership Award, UCLA Staff Assembly<ref>{{Cite web |title=2023 Recipients |url=https://staffassembly.ucla.edu/past-recipients/2023-recipients/ |access-date=2025-05-22 |website=UCLA Staff Assembly |language=en-US}}</ref> * 2024 Marcus Foundation Award<ref>{{Cite web |title=UCLA receives $2 million to develop regenerative medicine therapies for spinal cord injury |url=https://newsroom.ucla.edu/releases/ucla-receives-2-million-to-develop-regenerative-medicine-therapies-spinal-cord-injury |access-date=2025-05-22 |website=UCLA |language=en-us}}</ref>
== References == {{Reflist}}
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{{DEFAULTSORT:Butler, Samantha}} Category:Living people Category:Year of birth missing (living people) Category:American neuroscientists Category:British neuroscientists Category:American women neuroscientists Category:British women neuroscientists Category:Alumni of the University of Cambridge Category:Princeton University alumni Category:David Geffen School of Medicine at UCLA faculty Category:American women academics Category:British women academics Category:21st-century American women Category:21st-century British women scientists