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Elson S. Floyd College of Medicine

Faculty and Staff Directory


Assistant Professor

Education and Training

Ph.D. in Microbiology, East Tennessee State University
Postdoctoral Training in Neuroscience, Immunology, and Genetics, Duke University


We are interested in understanding how the nervous system regulates the innate immune response to pathogen infection and aging, two biological processes that are important for the survival and well-being of many living organisms.

1. Neural regulation of the innate immune response to pathogen infection

Fig. 1. The octopaminergic immuno-inhibitory pathway in C. elegans

Upon pathogen infection, cellular stress pathways and microbial killing pathways are rapidly activated by the host innate immune system. These pathways must be tightly regulated as insufficient immune responses exacerbate infection, whereas excessive responses lead to prolonged inflammation, tissue damage or even death. Increasing evidence indicates that the nervous system regulates the immune system to help maintain immunological homeostasis. However, the precise mechanisms of such regulation are not well understood. We have demonstrated that OCTR-1, a G protein-coupled receptor (GPCR), functions in the sensory neurons ASH and ASI to suppress the innate immune response to pathogen infection in Caenorhabditis elegans. Such regulation is achieved by inhibiting the expression of defense gens in pharyngeal and intestinal tissues in a cell non-autonomous manner. Recently, we identified neurotransmitter octopamine (OA) as an endogenous ligand for OCTR-1 in immune regulation and showed that the OA-producing RIC neurons function in the OCTR-1 neural circuit to suppress innate immunity. Therefore, an octopaminergic immunoinhibitory pathway emerges whereby OA released from RIC neurons act as a ligand of OCTR-1 that functions in the sensory ASH and ASI neurons to suppress the innate immune response in pharyngeal and intestinal tissues (Fig. 1). A number of questions, however, remain unanswered in this pathway. Ongoing efforts in my laboratory are addressing the following questions:

  1. Where do the immunomodulatory signals originate in the OCTR-1 neural circuit?
  2. Which neurons function downstream of ASH and ASI neurons?
  3. What is the nature of the immunomodulatory signals that are relayed from neural circuits to the non-neural tissues?
  4. What molecules mediate the innate immune response in the non-neural tissues?

The full complement of molecules, cells, and signaling cascades uncovered by these studies will be integrated together to elucidate the OCTR-1-dependent neural-immune regulatory circuit. As an excessive innate immune response has been linked to a myriad of human health conditions, our research on neural control of innate immunity could benefit the development of effective treatments for innate immune disorders.

2. Neural regulation of aging
We have demonstrated not only that neuronal OCTR-1 regulate innate immunity, but also that it controls the unfolded protein response (UPR), a cellular stress response related to the endoplasmic reticulum (ER) stress that can be triggered by pathogen infection. We found that OCTR-1 functions in ASH and ASI neurons to suppress UPR in young adult C. elegans, but not during development, coincident with the onset of UPR decline upon transition to adulthood. Increasing evidence suggests that age-associated decline of UPR activity is a causative factor in many age-onset diseases such as diabetes, cancer and neurodegenerative disorders. This raises the possibility that OCTR-1 and specific neurons may play important roles in aging and in the development of age-onset diseases, which has become our gateway to study neural regulation of aging. We are currently pursuing this new direction of research in the laboratory.

Selected Publications

  1. Sellegounder D, Yuan CH, Wibisono P, Liu Y, and Sun J. Octopaminergic signaling mediates neural regulation of innate immunity in Caenorhabditis elegans. MBio 2018, 9(5).
  2. Liu Y and Sun J. G protein-coupled receptors mediate neural regulation of innate immune responses in Caenorhabditis elegans. Receptors & Clinical Investigation 2017, 4: e1543.
  3. Liu Y, Sellegounder S, and Sun J.  Neuronal GPCR OCTR-1 regulates innate immunity by controlling protein synthesis in Caenorhabditis elegans. Scientific Reports 2016, 6:36832.
  4. Sun J, Aballay A and Singh V. Cellular responses to infections in C. elegans. Encyclopedia of Cell Biology, Sept 18, 2015
  5. Hall J*, Sun J*, Slade J, Kintner J, Bambino M, Whittimore J and Schoborg R. Host nectin-1 is required for efficient Chlamydia trachomatis serovar E development. Frontiers in cellular and infection microbiology. (* co-first author) 2014 Nov 6; 4:158.
  6. Sun J, Liu Y and Aballay A. Organismal regulation of XBP-1-mediated unfolded protein response during development and immune activation. EMBO reports 2012, 13: 855-860.Comment in: EMBO reports 2012, 13:766-768.
  7. Sun J, Singh V, Kajino-Sakamoto R and Aballay A. Neuronal GPCR controls innate immunity by regulating noncanonical unfolded protein response genes. Science 2011, 332:729-732.Comment in: Science 2011, 332:673-674.
  8. Schoborg RV, Sun J, Daniels C, Whittimore J and Kintner J. The Host Nectin-1 Protein Regulates Chlamydial Development. Proceedings of the 12th International Symposium on Human Chlamydial Infections. (Book chapter). 2010.
  9. Sun J and Schoborg R. The host adherens junction molecule nectin-1 is degraded by chlamydial protease-like activity factor (CPAF) in Chlamydia trachomatis-infected genital epithelial cells. Microbes and Infection2009, 11: 12-19.
  10. Sun J, Kintner J and Schoborg R. The host adherens junction molecule nectin-1 is down-regulated in Chlamydia trachomatis-infected genital epithelial cells. Microbiology 2008, 154: 1290-1299.
  11. Vanover J, Sun J, Deka S, Kintner J and Schoborg R. Herpes Simplex Virusco-infection induces C. trachomatis persistence through a novel mechanism. Microbiology 2007, 154: 971-978.
  12. Deka S, Vanover J, Sun J, Kintner J, Whittimore J and Schoborg R. An early event in the Herpes Simplex Virus type-2 replication cycle is sufficient to induce Chlamydia trachomatis persistence. Cellular Microbiology 2007, 9:725-737.
  13. Defoe DM, Adams LB, Sun, J, Wisecarver SN and Levine EM. Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation. Molecular Vision 2007, 13: 273-286.
  14. Schoborg R, Vanover J, Deka S, Sun J, Whittimore J and Kintner J. Herpes simple virus type 2 (HSV-2) co-infection induced chlamydial persistence requires an early event in the viral replication cycle. Proceedings of the Eleventh International Symposium on Human Chlamydial Infection. (Book chapter). 2006.

Sun Jingru
Assistant Professor

Sun Lab Website