Greg J. Bashaw, Ph.D.
135A Clinical Research Building
415 Curie Blvd.
Philadelphia, PA 19104
Fax: 215 573-7601
Brown University, 1990.
Ph.D. (Biological Sciences)
Stanford University, Mentor: Bruce Baker, 1997.
Description of Research ExpertiseResearch Interests
- Molecular mechanisms of axon growth and guidance during nervous system development.
- How axon guidance receptors specify attractive and repulsive signals and transmit these signals to the navigating growth cone.
- Non-canonical roles for guidance receptors as transcriptional regulators.
- Formation of Neural Circuits at the Midline
- Transcriptional Regulation of Neuronal Morphogenesis
- Generation of Neuronal Diversity
Key words: Axon guidance, developmental neuroscience, circuit assembly, Slit, Robo, Netrin, DCC, receptor signaling.
Description of Research
How axons in the developing nervous system successfully navigate to their correct targets is a fundamental problem in neurobiology. Understanding the mechanisms that mediate axon guidance will give important insight into how the nervous system is correctly wired during development and may have implications for therapeutic approaches to developmental brain disorders and nerve regeneration. Achieving this understanding will require unraveling the molecular logic that ensures the proper expression and localization of axon guidance cues and receptors, and elucidating the signaling events that regulate the growth cone cytoskeleton in response to guidance receptor activation.
The Slit ligand and Roundabout (Robo) receptors, and the Netrin ligand and DCC/UNC5 receptors are two important evolutionary conserved ligand/receptor systems that contribute to proper connectivity in both the vertebrate and invertebrate nervous systems. These molecules are also known to influence neuronal and mesodermal cell migration, suggesting that determining their function may have broad implications for understanding diseases of nervous system development, many of which have their root in defective cell migration and/or axon guidance. The research in my laboratory addresses the dynamics of axon guidance receptor expression and signaling, and exploits the powerful genetic and molecular approaches available in Drosophila.
We have also discovered that in addition to its canonical role in signaling locally to regulate growth cone movement and morphology, the Frazzled/DCC receptor can also act as a transcription factor to regulate gene expression. In this context, the receptor is cleaved to generate a soluble intracellular domain that can translocate to the nucleus where it activates transcription of key target genes.
A range of projects relating to axon guidance receptor regulation and signaling, employing a broad range of techniques in genetics, molecular biology, cell biology, imaging and biochemistry. For specific projects contact Dr. Bashaw.
Current Lab Personnel:
Elise Arbeille, Ph.D., Post-doctoral Fellow
Madhavi Gorla, Ph.D., Post-doctoral Fellow
Kate Laws, Ph.D., Postdoctoral Fellow
Samantha Russell, CAMB Graduate Student (DSRB)
Karina Chaudhari, CAMB Graduate Student(CPM)
Kevin Wiles, CAMB Graduate Student(GGR)
Yixin Zang, CAMB Graduate Student(DSRB)
Kelly Sullivan, CAMB Graduate Student (DSRB)
Daniel Schonhaut, NGG Graduate Student
Katherine Blocklove, Research Specialist
Henry Zhou, Undergraduate Researcher
Recent Lab Alumnae:
Celine Santiago, Ph.D. 2016, DRSB. Postdoctoral Fellow, Harvard, Ginty Lab
Melissa Hernandez, Ph.D. 2016, NGG.
Rebecca Chance, Ph.D. 2015, NGG. Postdoctoral Fellow, UC Berkeley, Ngai Lab
Alexandra Neuhaus-Follini, Ph.D. 2015, NGG. Postdoctoral Fellow, Johns Hopkins University, Johnston Lab
Mike O'Donnell, Ph.D. 2013, CAMB. Postdoctoral Fellow, Brandeis University, Sengupta Lab
Timothy Evans, Ph.D. 2013 Postdoctoral Fellow. Current, Assistant Professor of Biology, University of Arkansas
Ethan Rohrbach, Undergraduate Researcher 2015-2017, Graduate Student UCLA
Description of Other ExpertiseOutreach
In addition to our research program, students and postdoctoral fellows in the lab contribute to a science education outreach project designed to enhance scientific aptitude and literacy in Philadelphia public high schools. This project is funded by the National Science Foundation (IOS-1355181)and was developed in partnership with Dr. Jamie Shuda. We are in our fourth year of the program and a brief description follows.
Over the last ten years, local under-served and impoverished school systems have increasingly felt the burden of lack of funding and limited resources for science education. The School District of Philadelphia has seen historic lay offs and crippling budget cuts. It is because of these challenges that we are developing a science outreach program. Using an established and successful outreach program called Project BioEYES (www.bioeyes.org) as the foundation of our work, we will (1) host one high school teacher per year for a 6-week summer research position; (2) develop a set of classroom curricula focused on using flies to create modules designed to foster an understanding of neuronal development and the relationship between genes and behavior; and (3) evaluate student learning and enthusiasm for the classroom science experiments and teachers’ overall experience in our outreach project.
Winnie Chan, Furness High School (Summer 2015-2017)
Galeet Cohen, Central High School (Summer 2017)
Bob Herbstritt, Central High School (Summer 2016)
Elizabeth Curry, Sayre High School (Summer 2014)
Selected PublicationsCeline Santiago and Greg J. Bashaw: Islet coordinately regulates motor axon guidance and dendrite targeting through the Frazzled/DCC receptor. Cell Reports 18(7): 1646-1659, February 2017.
Melissa Hernandez-Fleming, Ethan Rohrbach and Greg J. Bashaw: Sema-1a reverse signaling promotes midline crossing in response to secreted Semaphorins. Cell Reports 18(1): 174-184, January 2017.
Rebecca K. Chance and Greg J. Bashaw: Slit-dependent endocytic trafficking of the Robo receptor is required for Son of Sevenless recruitment and midline axon repulsion. PLoS Genetics. PLoS, Page: 1-27, September 2015 Notes: See Perspective by Frederic Charron PLoS Genetics 11(9): e1005441. doi:10.1371/journal.pgen.1005441.
Alexandra Neuhaus-Follini and Greg J. Bashaw: The Intracellular Domain of the Frazzled/DCC Receptor Is a Transcription Factor Required for Commissural Axon Guidance. Neuron. Elsevier, 87(4): 751-763, August 2015.
Timothy A. Evans, Celine Santiago, Elise Arbeille and Greg J. Bashaw: Robo2 acts in trans to inhibit Slit-Robo1 repulsion in pre-crossing commissural axons. eLife. eLife Sciences,(doi: 10.7554/eLife.08407), 1-25, July 2015 Notes: The following authors contributed equally to this work Timothy A. Evans, Celine Santiago
Celine Santiago, Juan-Pablo Labrador and Greg J. Bashaw: The homeodomain transcription factor Hb9 controls axon guidance in Drosophila through the regulation of Robo receptors. Cell Reports 7(1): 153-165. April 2014.
Aref Arzan Zarin, Jamshid Asadzadeh1, Karsten Hokamp, Daniel McCartney, Long Yang, Greg J. Bashaw and Juan-Pablo Labrador: A Transcription Factor Network Coordinates Attraction, Repulsion, and Adhesion Combinatorially to Control Motor Axon Pathway Selection. Neuron 81(6): 1297-1311, March 2014.
Michael O'Donnell and Greg J. Bashaw: Src inhibits midline axon crossing independent of Frazzled/DCC receptor tyrosine phosphorylation. Journal of Neuroscience 33(1): 305-314, January 2013.
Timothy A. Evans and Greg J. Bashaw: Functional Diversity of Robo Receptor Immunoglobulin Domains Promotes Distinct Axon Guidance Decisions. Current Biology 20(6), March 2010.
Long Yang, David S. Garbe and Greg J. Bashaw: A frazzled/DCC-dependent transcriptional switch regulates midline axon guidance. Science 324(5929): 944-7, May 2009.