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Christopher Deppmann

Christopher Deppmann

Professor, Biology

Primary Location
314 Physical Life Sciences Building
Primary Phone Number
434.260.1572
Email
[email protected]
Website
http://www.deppmannlab.com/

Bio & Overview

Background and Summary of Previous Findings: Neural development involves competition at many levels, whether it be axons innervating a target or synapses refining a connection. Over 50 years ago, Viktor Hamburger and Rita Levi-Montalcini put forth the first hypothesis explaining competition in the PNS. Their hypothesis posited that neuronal survival during development is dependent on a limited supply of target-derived trophic factors. For a target-derived factor to influence neuronal survival, its signal must get from the tip of the innervating axon back to the neuronal cell body, a particularly daunting task in the long neurons of the PNS. Using sympathetic neurons as a model system, we and others have directly demonstrated that these long-distance signals are transduced via a retrograde signaling endosome carrying target-derived nerve growth factor (NGF) and its cognate receptor, TrkA. Once this signaling endosome arrives at the cell body, the activated TrkA receptor initiates pro-survival events. The hypothesis of Hamburger and Levi-Montalcini explains neuronal competition at the population level; the supply of NGF at the target is only sufficient to support survival of a certain number of neurons. At the level of the individual cell however, the basis of neuronal competition for survival is less clear. If all cells are capable of endosomal retrograde signaling, what makes one cell more competitive, more successful at taking up NGF and therefore more likely to survive, than its neighbor? Is it due to varying concentrations of trophic factor, and subsequently, differences in magnitude of signal transduction? Or, alternatively, are there factors that give some neurons a competitive advantage? We recently found that neuronal competition at the individual cell level involves a complex combination of events (Deppmann et al., Science). We used mathematical modeling, biochemical, and genetic approaches to show that, in the PNS, the likelihood of neuronal survival is critically dependent on a sensitization process initiated by target innervation and strengthened by a series of positive-feedback loops. We found that in addition to initiating expression of survival factors, the retrogradely transported NGF-TrkA signaling complex also increases expression of TrkA, thereby increasing the magnitude of NGF-TrkA pro-survival signaling. We also discovered that the duration of NGF-TrkA pro-survival signaling is variable, and regulated in an NGF-dependent manner. The exact mechanism of this regulation is unknown. NGF also influences a complex protection/punishment mechanism affecting neuronal survival. We found that, in sympathetic neurons, NGF signaling induces a cell to increase secretion of BDNF and NT4 which, via p75 signaling, can kill or "punish" neighboring sympathetic neurons in a paracrine manner. High NGF-TrkA signaling protects neurons from this punishment signal while low NGF-TrkA signaling leaves cells vulnerable. This finding is consistent with the 1972 theory of Meinhardt and Gierer suggesting that self-activation and lateral inhibition underlie pattern formation. We feel that these three elements--target-initiated sensitization, protection from punishment, and punishment--are essential for the rapid and robust competition implicit within the neurotrophic factor hypothesis. Current Projects In the Lab There are several projects that are available which will be scaled for undergrad students, grad students, or post-docs. Without getting bogged down with too much detail, here are a few potential projects available for people to work on. Of course these will evolve as we move forward. 1. Examine neuronal competition for survival in complex populations of neurons. Our previous work exploited the relative simplicity of the sympathetic nervous system to delineate the rules for competition. Other populations of neurons, such as those in the dorsal root ganglia, are more complex. We hypothesize that in these more complex systems the sensitization process is likely to remain very similar to what we observe in the sympathetic nervous system. Punishment signaling may function differently however, as the punishment cues identified in sympathetic neurons--BDNF-induced p75 signaling for instance--would actually have trophic effects in some neighboring TrkB positive neurons. 2. Delineate signaling underlying protection and punishment cross-talk This has been a long-standing issue in the trophic factor field, however very little is known. We have developed several promising leads as to how these signaling pathways communicate with one another. Understanding how these antagonistic programs communicate with each other not only has implications for the development of the nervous system, but may also lead to insights into pathologies such as neuroblastoma or neurodegeneration. 3. Examine if signaling programs involved in competition for survival are also involved in competition for synaptic connectivity After a developmental critical period, neurons no longer rely on target derived trophic factor for survival even though its availability and signaling persist into adulthood. If this signaling is not functioning as a pro-survival cue, what is it doing after this critical period? Synapse formation is an attractive candidate for this since it occurs after competition for survival. Therefore, this project will center around determining whether this signaling is important for synapse formation. 4. Examine the role of novel target derived neurotrophin regulated genes in developmental processes such as competition, axon extension, axon branching, changes in metabolism, and acquisition of neurotransmitter phenotype. We previously performed a microarray analysis to identify genes regulated by target derived trophic factor in vivo. There are still 100's of interesting genes yet to be characterized in these processes. We have already begun characterizing genes that are important for cytoskeletal re-arrangement, signaling endosome function, and axon guidance. 5. Determine if re-engagement of developmental competition programs can participate in diseases of the nervous system. The notion of pathologies co-opting developmental programs has been proposed in certain types of cancer as well as in complications in nerve regeneration. While there has been significant progress made identifying causative factors underlying neurodegenerative pathologies, the mechanism by which the pathology spreads to asymptomatic neurons in diseases such as Parkinson's or ALS has been largely unexplored. To learn more about potential research projects, visit my lab webpage.

Academic Information

Department
Biology
Academic Title
Associate Professor

Primary Education

  • BS, Biomedical Sciences/Chemistry, Western Michigan University, 1997
  • PhD, Biochemistry & Molecular Biology, Purdue University, 2003
  • Postdoc, Developmental Neuroscience, John Hopkins University, 2009

Other Appointments

  • Associate Professor, Biomedical Engineering
  • Cell Biology
  • Associate Professor, Neuroscience
  • Assistant Professor, BMBG
  • Assistant Professor, MCDB

Other Affiliations

  • MSTP
  • Assistant Professor, BIMS
  • BIMS

Research Interests

Elucidating and Understanding the Mechanisms Underlying Nervous System Development

Research Disciplines

  • Biochemistry
  • Biotechnology
  • Cell and Developmental Biology
  • Development, Stem Cells & Regeneration
  • Metabolism
  • Molecular Biology
  • Neuroimmunology
  • Neuroscience

Research Opportunities

  • Cellular and Molecular Metabolism
  • Development, Stem Cells & Regeneration
  • Molecular and Systems Neuroscience
  • Neuroimmunology
  • Neuroscience

PhD Programs

  • Biomedical Engineering
  • Neuroscience

Selected Publications

2023

Deppmann, C. D., & Zunder, E. R. (2023). The good, the bald, and the hairy: A mechanosensor meets its fate at the target. DEVELOPMENTAL CELL, 58(20), 2013-2014. doi:10.1016/j.devcel.2023.08.027

Tang, Q., Godschall, E., Brennan, C. D., Zhang, Q., Abraham-Fan, R. -J., Williams, S. P., . . . Guler, A. D. (2023). Leptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network. SCIENCE ADVANCES, 9(34). doi:10.1126/sciadv.adh9570

Mason, A. J., Keeler, A. B., Kabir, F., Winckler, B., & Deppmann, C. (2023). Sympathetic neurons secrete retrogradely transported TrkA on extracellular vesicles. SCIENTIFIC REPORTS, 13(1). doi:10.1038/s41598-023-30728-3

Kumar, S., Budhathoki, S., Oliveira, C. B., Kahle, A. D., Calhan, O. Y., Lukens, J. R., & Deppmann, C. D. (2023). Role of the caspase-8/RIPK3 axis in Alzheimer's disease pathogenesis and Aβ-induced NLRP3 inflammasome activation. JCI INSIGHT, 8(3). doi:10.1172/jci.insight.157433

2022

Keeler, A. B., Van Deusen, A. L., Cheng, I., Williams, C. M., Goggin, S. M., Hirt, A. K., . . . Calhan, Y. (2022). A developmental atlas of somatosensory diversification and maturation in the dorsal root ganglia by single-cell mass cytometry. NATURE NEUROSCIENCE, 25(11), 1543-+. doi:10.1038/s41593-022-01181-8

2021

Yong, Y., Hunter-Chang, S., Stepanova, E., & Deppmann, C. (2021). Axonal spheroids in neurodegeneration. MOLECULAR AND CELLULAR NEUROSCIENCE, 117. doi:10.1016/j.mcn.2021.103679

2020

Yong, Y., Gamage, K., Cushman, C., Spano, A., & Deppmann, C. (2020). Regulation of degenerative spheroids after injury. SCIENTIFIC REPORTS, 10(1). doi:10.1038/s41598-020-71906-x

Pathak, A., Clark, S., Bronfman, F. C., Deppmann, C. D., & Carter, B. D. (2021). Long-distance regressive signaling in neural development and disease. WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY, 10(2). doi:10.1002/wdev.382

Podyma, B., Johnson, D. -A., Sipe, L., Remcho, T. P., Battin, K., Liu, Y., . . . Guler, A. D. (2020). The p75 neurotrophin receptor in AgRP neurons is necessary for homeostatic feeding and food anticipation. ELIFE, 9. doi:10.7554/eLife.52623

Kuhn, K. D., Edamura, K., Bhatia, N., Cheng, I., Clark, S. A., Haynes, C. V., . . . Keeler, A. B. (2020). Molecular dissection of TNFR-TNFα bidirectional signaling reveals both cooperative and antagonistic interactions with p75 neurotrophic factor receptor in axon patterning. MOLECULAR AND CELLULAR NEUROSCIENCE, 103. doi:10.1016/j.mcn.2020.103467

Yong, Y., Hughes, C., & Deppmann, C. (2020). A Microfluidic Culture Platform to Assess Axon Degeneration. AXON DEGENERATION, 2143, 83-96. doi:10.1007/978-1-0716-0585-1_7

2019

Yong, Y., Gamage, K., Cheng, I., Barford, K., Spano, A., Winckler, B., & Deppmann, C. (2019). p75NTR and DR6 Regulate Distinct Phases of Axon Degeneration Demarcated by Spheroid Rupture. JOURNAL OF NEUROSCIENCE, 39(48), 9503-9520. doi:10.1523/JNEUROSCI.1867-19.2019

2018

Ray, S., Tillo, D., Assad, N., Ufot, A., Deppmann, C., Durell, S. R., . . . Vinson, C. (2018). Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 501(4), 905-912. doi:10.1016/j.bbrc.2018.05.080

Cheng, I., Jin, L., Rose, L. C., & Deppmann, C. D. (2018). Temporally restricted death and the role of p75NTR as a survival receptor in the developing sensory nervous system. DEVELOPMENTAL NEUROBIOLOGY, 78(7), 701-717. doi:10.1002/dneu.22591

Barford, K., Keeler, A., McMahon, L., McDaniel, K., Yap, C. C., Deppmann, C. D., & Winckler, B. (2018). Transcytosis of TrkA leads to diversification of dendritic signaling endosomes. SCIENTIFIC REPORTS, 8. doi:10.1038/s41598-018-23036-8

2017

Barford, K., Keeler, A., Deppmann, C., & Winckler, B. (2017). TrkA Bumps into Its Future Self. DEVELOPMENTAL CELL, 42(6), 557-558. doi:10.1016/j.devcel.2017.09.002

Keeler, A. B., Suo, D., Park, J., & Deppmann, C. D. (2017). Delineating neurotrophin-3 dependent signaling pathways underlying sympathetic axon growth along intermediate targets. MOLECULAR AND CELLULAR NEUROSCIENCE, 82, 66-75. doi:10.1016/j.mcn.2017.04.011

Gamage, K. K., Cheng, I., Park, R. E., Karim, M. S., Edamura, K., Hughes, C., . . . Deppmann, C. D. (2017). Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons (vol 27, pg 890, 2017). CURRENT BIOLOGY, 27(8), 1250. doi:10.1016/j.cub.2017.03.058

Keeler, A. B., & Deppmann, C. D. (2017). The evolutionary origins of antagonistic neurotrophin signaling. JOURNAL OF CELL BIOLOGY, 216(5), 1223-1225. doi:10.1083/jcb.201702115

Sipe, L. M., Yang, C., Ephrem, J., Garren, E., Hirsh, J., & Deppmann, C. D. (2017). Differential sympathetic outflow to adipose depots is required for visceral fat loss in response to calorie restriction. NUTRITION & DIABETES, 7. doi:10.1038/nutd.2017.13

Smith, C. J., Wheeler, M. A., Marjoram, L., Bagnat, M., Deppmann, C. D., & Kucenas, S. (2017). TNFa/TNFR2 signaling is required for glial ensheathment at the dorsal root entry zone. PLOS GENETICS, 13(4). doi:10.1371/journal.pgen.1006712

Gamage, K. K., Cheng, I., Park, R. E., Karim, M. S., Edamura, K., Hughes, C., . . . Deppmann, C. D. (2017). Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons. CURRENT BIOLOGY, 27(6), 890-896. doi:10.1016/j.cub.2017.01.062

Barford, K., Deppmann, C., & Winckler, B. (2017). The Neurotrophin Receptor Signaling Endosome: Where Trafficking Meets Signaling. DEVELOPMENTAL NEUROBIOLOGY, 77(4), 405-418. doi:10.1002/dneu.22427

2016

Martorella, M., Barford, K., Winckler, B., & Deppmann, C. D. (2017). Emergent Role of Coronin-1a in Neuronal Signaling. NEUROTROPHINS, 104, 113-131. doi:10.1016/bs.vh.2016.10.002

Wheeler, M. A., Smith, C. J., Ottolini, M., Barker, B. S., Purohit, A. M., Grippo, R. M., . . . Guler, A. D. (2016). Genetically targeted magnetic control of the nervous system. NATURE NEUROSCIENCE, 19(5), 756-+. doi:10.1038/nn.4265

2015

Suo, D., Park, J., Young, S., Makita, T., & Deppmann, C. D. (2015). Coronin-1 and Calcium Signaling Governs Sympathetic Final Target Innervation. JOURNAL OF NEUROSCIENCE, 35(9), 3893-3902. doi:10.1523/JNEUROSCI.4402-14.2015

Suo, D., Park, J., & Deppmann, C. D. (2015). Coronin-1 mediates hierarchal neurotrophin signaling required for sympathetic neuron target innervation. INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 47, 108-109. doi:10.1016/j.ijdevneu.2015.04.296

2014

Wheeler, M. A., Heffner, D. L., Kim, S., Espy, S. M., Spano, A. J., Cleland, C. L., & Deppmann, C. D. (2014). TNF-α/TNFR1 Signaling Is Required for the Development and Function of Primary Nociceptors. NEURON, 82(3), 587-602. doi:10.1016/j.neuron.2014.04.009

Parameswaran, N., Dewals, B. G., Giles, T. C., Deppmann, C., Blythe, M., Vanderplasschen, A., . . . Haig, D. (2014). The A2 gene of alcelaphine herpesvirus-1 is a transcriptional regulator affecting cytotoxicity in virus-infected T cells but is not required for malignant catarrhal fever induction in rabbits. VIRUS RESEARCH, 188, 68-80. doi:10.1016/j.virusres.2014.04.003

Sokolowski, J. D., Gamage, K. K., Heffron, D. S., LeBlanc, A. C., Deppmann, C. D., & Mandell, J. W. (2014). Caspase-mediated cleavage of actin and tubulin is a common feature and sensitive marker of axonal degeneration in neural development and injury. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2. doi:10.1186/2051-5960-2-16

2013

Suo, D., Park, J., Harrington, A. W., Zweifel, L. S., Mihalas, S., & Deppmann, C. D. (2014). Coronin-1 is a neurotrophin endosomal effector that is required for developmental competition for survival. NATURE NEUROSCIENCE, 17(1), 36-45. doi:10.1038/nn.3593

Sokolowski, J. D., Heffron, D. S., Deppmann, C., LeBlanc, A. C., & Mandell, J. W. (2013). Caspase-generated neoepitopes as markers of axonal degeneration in neural development and injury. FASEB JOURNAL, 27. Retrieved from https://www.webofscience.com/

2012

Mitchell, D. J., Blasier, K. R., Jeffery, E. D., Ross, M. W., Pullikuth, A. K., Suo, D., . . . Pfister, K. K. (2012). Trk Activation of the ERK1/2 Kinase Pathway Stimulates Intermediate Chain Phosphorylation and Recruits Cytoplasmic Dynein to Signaling Endosomes for Retrograde Axonal Transport. JOURNAL OF NEUROSCIENCE, 32(44), 15495-15510. doi:10.1523/JNEUROSCI.5599-11.2012