Erik A Lundquist
- Professor
- Associate Vice Chancellor for Research
Contact Info
Personal Links
- 0000-0001-6819-4815
- Google Scholar Profile
Biography —
My primary research interest is developmental neurobiology, or how nervous systems form during the process of organismal development. My lab investigates two fundamental events in nervous system development: 1) the migration of neuronal stem cells and neurons to their final positions (e.g. to the cortical layers in the cerebrum and cerebellum); and 2) wiring the nervous system by the directed guidance of neuronal axons to their proper synaptic targets (e.g. other neurons or muscles). I use a genetic and genomic approach in the model organism nematode worm Caenorhabditis elegans, which despite being a soil-dwelling roundworm from which we diverged ~600 million years ago, has a nervous system and genome very similar to our own.
I earned a B.S. degree in Biological Sciences at the University of Nebraska, and a Ph.D. degree in Genetics from the University of Minnesota with Dr. Robert K. Herman and Dr. Jocelyn E. Shaw. I then completed post-doctoral research at the University of California-San Francisco with Dr. Cornelia I. Bargmann, with support from the Howard Hughes Medical Institute, the Damon Runyon Cancer Research Foundation, and the National Institutes of Health.
I am currently a Professor in the Department of Molecular Biosciences, a position I started in 2000. I am co-Investigator on the Center for Molecular Analysis of Disease Pathways NIH COBRE project, and I am a member of the KU Center for Genomics and the KU Cancer Center. I also serve as Associate Vice-Chancellor for Research for the University of Kansas.
Education —
Research —
Research in the Lundquist lab involves an integrated set of genetic, genomic, microscopic, and computational tools to decipher fundamental genetic mechanisms underlying the development of the nervous system. These studies focus on the nervous system of the model organism nematode worm Caenorhabditis elegans. Humans share a common ancestor with C. elegans, the urbilaterian ancestor of all bilaterally-symmetric animals that lived ~600 million years ago. By the time humans diverged from C. elegans, a vast majority of the genetic, cellular, and developmental mechanisms controlling animal development and differentiation had already evolved. Thus, what is learned about C. elegans genetics and development is largely applicable to humans.
- A new model of directed growth cone migration: the polarity/protrusion model
Analyzing the effects of guidance ligands and receptors on growth cone morphology during outgrowth led to a new model of directed growth cone migration involving growth cone polarity and protrusion. Our work indicates that UNC-6/Netrin first polarizes the growth cone via the UNC-5 receptor, and then regulates growth cone protrusion based upon this polarity (the polarity/protrusion. UNC-6/Netrin inhibits protrusion via UNC-5 receptor ventrally, close to the UNC-6/Netrin source, and stimulates protrusion dorsally via the UNC-40 receptor, away from the UNC-6/Netrin source. This asymmetry of protrusive activities results in directed growth cone protrusion and outgrowth. This model is fundamentally distinct from the existing chemotactic gradient model of axon guidance that has predominated, which postulates that growth cones follow gradients of secreted chemoattractants and chemorepellants, and that UNC-40 was the “attractive” receptor and UNC-5 was the “repulsive” receptor - Mechanistic and functional transcriptomic analysis of cell migration
Directional cell migration is central to nervous system development. Dr. Lundquist uses the Q neuroblasts in C. elegans as a model for directional neuronal migration. QL on the left migrates to the posterior, and QR on the right to the anterior. Posterior migration of the QL descendants is controlled by the Hox transcription factor MAB-5. Dr. Lundquist uses RNA-seq combined with mutant analysis to identify potential transcriptional targets of MAB-5 that regulate Q migrations. These studies have revealed that MAB-5 primarily controls the expression of secreted and transmembrane molecules, indicating that it directly regulates cell-substrate interactions. - Linking guidance receptors to cytoskeletal mechanisms of axon guidance
The early 1990s witnessed the discovery of many of the ligands and their receptors that control axon guidance (e.g. Netrin, Slit, Semaphorins). At the time, little was known about the cytoplasmic and cytoskeletal signaling mechanisms that linked guidance receptors to growth cone outgrowth. Dr. Lundquist’s work has revealed signaling mechanisms involving Rac GTPases and their regulators and the cytoskeletal molecules that mediate the effects of axon guidance receptors. - Rho-family GTPase signaling in axon guidance in vivo
In the course of studying their roles in axon guidance, Dr. Lundquist has made significant contributions to understanding the function of Rho-family small GTPases, most notably Rac. Dr. Lundquist’s work was among the first to move from cell culture models to analyze Rac function in vivo in developmental events. Using transgenic expression of activated forms of the molecules, Dr. Lundquist has discovered the signaling mechanisms employed downstream of Rac and Cdc42 GTPases in growth cone protrusion during outgrowth. Additionally, Dr. Lundquist demonstrated in vivo that distinct Rac regulators control Rac GTPases in specific cellular events. For example, the Rac GEF TIAM-1 regulates Rac in stimulation of protrusion, whereas the UNC-73/Trio GEF regulates Rac function in inhibiting protrusion. These are fundamental insights into how Racs can control multiple cellular events in the same cell by interacting with distinct GTPases. This idea was presumed to be the case because of the limited number of Rac GTPases (<10) and the greater number of Rac GEFs (>20), and Dr. Lundquist’s work demonstrated that this is the case in vivo. Recent work has demonstrated a role of the RHO-1 GTPase in inhibiting growth cone protrusion by restricting growth cone microtubule entry.
Teaching —
BIOL 405 Laboratory in Genetics (Fall 2024)
I currently teach BIOL 405 Laboratory in Genetics. I taught BIOL 417 Biology of Development from 2001 to 2018. I also have taught a variety of upper-level graduate courses including BIOL 807 Introduction to Molecular Biosciences.
Outside of the classroom, I teach undergraduates, graduate students, and post-doctoral scientists in the laboratory. This involves training and mentoring them on the scientific process and how to do research and to be a scientist, honing their analytical and experimental skills to successfully execute research projects.
Selected Publications —
See all articles by Erik A. Lundquist on PubMed.
A new model of directed growth cone migration: the polarity/protrusion model
- Hooper, K.M. and Lundquist, E.A. Short-and long-range roles of UNC-6/Netrin in dorsal-ventral axon guidance in vivo in Caenorhabditis elegans. bioRxiv 2024 Apr 23:2024. doi: 10.1101/2024.04.23.590737. Preprint.
- Mahadik, S.S., and Lundquist, E.A. TOM-1/Tomosyn acts with the UNC-6/Netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans. Development 2023 Apr 1;150(7):dev201031. doi: 10.1242/dev.201031.
- Gujar, M., Sundararajan, L., Stricker, A., and Lundquist, E.A. Control of Growth Cone Polarity, Microtubule Accumulation, and Protrusion by UNC-6/Netrin and Its Receptors in Caenorhabditis elegans. Genetics 2018 Sep;210(1):235-255. doi: 10.1534/genetics.118.301234. Epub 2018 Jul 25.
- Gujar, M., Stricker, A., and Lundquist, EA. Flavin monooxygenases regulate Caenorhabditis elegans axon guidance and growth cone protrusion with UNC-6/Netrin signaling and Rac GTPases. PLoS Genetics 2017 August 31,13:8. PMC5597259
- Norris, A.D., and Lundquist, E.A. UNC-6/Netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone protrusion in vivo in C. elegans.Development 2011, 138:4433-4442. PMC3177313.
Mechanistic and functional transcriptomic analysis of cell migration
- Paolillo, V.K., Ochs, M.E., and Lundquist, E.A. MAB-5/Hox regulates the Q neuroblast transcriptome, including cwn-1/Wnt, to mediate posterior migration in Caenorhabditis elegans. Genetics 2024 Apr 23:iyae045. doi: 10.1093/genetics/iyae045
- Ochs, M.E., McWhirter, R.M., Unckless, R.L., Miller III, D.M, and Lundquist, E.A. Caenorhabditis elegans ETR-1/CELF has broad effects on the muscle cell transcriptome, including genes that regulate translation and neuroblast migration. BMC Genomics. 2022 Jan 6;23(1):13. doi: 10.1186/s12864-021-08217-6. PMC8734324.
- Lang, A.E., and Lundquist, E.A. The Collagens DPY-17 and SQT-3 Direct Anterior-Posterior Migration of the Q Neuroblasts in C. elegans. Journal of Developmental Biology, 2021 Feb 19;9(1):7. PMC8006237.
- Ochs, M.E., Josephson, M.P., and Lundquist, E.A. The Predicted RNA-Binding Protein ETR-1/CELF1 Acts in Muscles To Regulate Neuroblast Migration in Caenorhabditis elegans. G3: Genes Genomes, Genetics. 2020 Jul 7;10(7):2365-2376. doi: 10.1534/g3.120.401182. PMC7341121.
- Josephson, M., Chai, Y., Ou, G., and Lundquist E.A. EGL-20/Wnt and MAB-5/Hox Act Sequentially to Inhibit Anterior Migration of Neuroblasts in C. elegans. 2016 PLoS One. 2016 Feb 10;11(2):e0148658. PMC4749177.
Linking guidance receptors to cytoskeletal mechanisms of axon guidance
- Snehal S. Mahadik, Emily K. Burt, Erik A. Lundquist. SRC-1 controls growth cone polarity and protrusion with the UNC-6/Netrin receptor UNC-5 in Caenorhabditis elegans. bioRxiv 2023.05.20.541322; doi: https://doi.org/10.1101/2023.05.20.541322 (accepted for publication in PLoS One).
- Mahadik, S.S. and Lundquist, E.A. A short isoform of the UNC-6/Netrin receptor UNC-5 is required for growth cone polarity and robust growth cone protrusion in Caenorhabditis elegans. Front Cell Dev Biol. 2023 Aug 15;11:1240994. doi: 10.3389/fcell. 2023.1240994. PMC10464613.
- Mahadik, S.S., Burt, E.K., and Lundquist, E.A. SRC-1 controls growth cone polarity and protrusion with the UNC-6/Netrin receptor UNC-5 in Caenorhabditis elegans. BioRxiv. 2023 May 20;2023.05.20.541322. doi: 10.1101/2023.05.20.541322. PMC10245697.
- Demarco, R.S., Struckhoff, E.C., and Lundquist, E.A. The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance. PLoS Genetics 2012, 8:4, e1002665. PMC3343084.
- Zemer Gitai, Timothy W. Yu, Erik A. Lundquist, Marc Tessier-Lavigne and Cornelia I. Bargmann. “The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through Enabled and, in parallel, Rac and UNC-115/AbLIM.” Neuron 2003, 37: 53-65. PMID: 12526772.
Rho-family GTPase signaling in axon guidance in vivo
- Gujar, M., Stricker, A., and Lundquist, E.A. RHO-1 and the Rho GEF RHGF-1 interact with UNC-6/Netrin signaling to regulate growth cone protrusion and microtubule organization in Caenorhabditis elegans. PLoS Genetics 2019 Jun 24;15(6):e1007960. PMC6611649
- Norris, A.D, Sundararajan, L., Morgan, D.E., Roberts, Z.J., and Lundquist, E.A. UNC-6/Netrin receptors UNC-40/DCC and UNC-5 inhibit growth cone filopodial protrusion using UNC-73/Trio, Rac GTPases, and UNC-33/CRMP. 2014. Development 141:22, 4395-405. PMC4302909.
- Demarco, R.S., Struckhoff, E.C., and Lundquist, E.A. The Rac GTP exchange factor TIAM-1 acts with CDC-42 and the guidance receptor UNC-40/DCC in neuronal protrusion and axon guidance. PLoS Genetics 2012, 8:4, e1002665. PMC3343084.
- Struckhoff, E.C. and Lundquist, E.A. “The Actin-Binding Protein UNC-115 Is an Effector of Rac Signaling During Axon Pathfinding in C. elegans.” Development 130: 693-704, 2003. PMC12506000.
- Lundquist, Erik A., Reddien, Peter W., Hartwieg, Erika, Horvitz, H. Robert, and Bargmann, Cornelia I. “Three C. elegans Rac Proteins and Several Alternative Rac Regulators Control Axon Guidance, Cell Migration, and Apoptotic Cell Phagocytosis.” Development 128: 4475-4488, 2001. PMC11714673.