Department of Immunology

Naeha Subramanian, Ph.D.

ASSOCIATE PROFESSOR, INSTITUTE FOR SYSTEMS BIOLOGY
AFFILIATE ASSOCIATE PROFESSOR, IMMUNOLOGY

Naeha Subramanian graduated with a Bachelor’s degree in Microbiology and a Master’s in Biomedical Science from the University of Delhi. She received her Ph.D. from the National Institute of Immunology at Jawaharlal Nehru University in New Delhi, India. After completing postdoctoral training at the National Institutes of Health, she joined the Institute for Systems Biology as an Assistant Professor in 2014 and was promoted to Associate Professor in 2021. She joined UW Immunology as an Affiliate Assistant Professor in 2016 and was promoted to Affiliate Associate Professor in 2022.

CONTACT INFO

Institute for Systems Biology
401 Terry Avenue North
Seattle, WA 98109-5263
(206) 732-1226

RESEARCH AREAS

Autoimmunity and Autoinflammation
Innate Immunity

LAB MEMBERS

Lab Website

Team | The Subramanian Lab (isbscience.org)

RESEARCH

The Subramanian lab works in the areas of innate immunity and systems immunology. We employ experimental and computational approaches to tackle basic questions in innate immunity, its role in host defense against pathogens and the development of complex diseases. In particular, we are interested in exploring the functions and regulation of a class of cytosolic immune sensors called the Nod-like receptors (or NLRs; Nucleotide-binding domain leucine-rich repeat containing receptors) and how their dysregulation manifests disease. NLRs are the largest known family of cytosolic sensor proteins that detect ligands of microbial or endogenous origin and stimulate immune activities. Upon activation, some members of the NLR family such as NLRP3, NLRP1, and NLRC4 form a macromolecular signaling complex called the inflammasome that acts as a scaffold for activation of caspase-1 leading to processing and secretion of the potent inflammatory cytokine IL-1beta. Others such as NOD1 and NOD2 form signaling platforms that activate NF-kappaB. However, emerging aspects of NLR biology also point to several non-canonical functions that extend beyond inflammation to include tissue homoeostasis, autophagy, embryonic development and transcriptional regulation. In humans, twenty-two NLRs have been identified. Gain-of-function mutations in NLRs are associated with a host of severe human cancers, autoinflammatory and autoimmune diseases, however to date the signaling cascades and immunological roles most NLRs remain unknown. We apply unbiased omic approaches (transcriptional profiling, proteomics, computational analyses and functional assays) to define NLR response phenotypes and associated signaling pathways. We also employ imaging to study the role of intracellular positioning to sub-cellular structures in the regulation of NLRs and inflammasomes. Our goal is to discern novel cellular functions and regulatory mechanisms of NLRs, ultimately devising new strategies for therapeutic modulation of NLR function in disease.

The lab also works in the area of human immunology, especially systems-level studies investigating the heterogeneity of the human immune response during Lyme Disease caused by the spirochaete Borrelia burgdorferi. An outstanding question in the field is why some patients resolve disease with antibiotic therapy while others progress to post-treatment disease. Using systems biology approaches we are dissecting the mechanisms of pathogen clearance and deriving immune correlates of disease in patients.

PUBLICATIONS

  1. Akhade, A. S., Atif, S. M., Lakshmi, B. S., Dikshit, N., Hughes, K. T., Qadri, A., & Subramanian, N. (2020). Type 1 interferon-dependent repression of NLRC4 and iPLA2 licenses down-regulation of Salmonella flagellin inside macrophages. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.2002747117
  2. Rommereim, L. M., Akhade, A. S., Dutta, B., Hutcheon, C., Lounsbury, N. W., Rostomily, C. C., Savan, R., Fraser, I. D. C., Germain, R. N., & Subramanian, N. (2020). A small sustained increase in NOD1 abundance promotes ligand-independent inflammatory and oncogene transcriptional responses. Science Signaling, 13(661). https://doi.org/10.1126/scisignal.aba3244
  3. Su, Y., Chen, D., Yuan, D., Lausted, C., Choi, J., Dai, C. L., Voillet, V., Duvvuri, V. R., Scherler, K., Troisch, P., Baloni, P., Qin, G., Smith, B., Kornilov, S. A., Rostomily, C., Xu, A., Li, J., Dong, S., Rothchild, A., Heath, J. R. (2020). Multi-omics resolves a sharp disease-state shift between mild and moderate COVID-19. Cell, S0092867420314446. https://doi.org/10.1016/j.cell.2020.10.037
  4. Idso, M. N., Akhade, A. S., Arrieta-Ortiz, M. L., Lai, B. T., Srinivas, V., Hopkins, J. P., Gomes, A. O., Subramanian, N., Baliga, N., & Heath, J. R. (2020). Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria. Chemical Science, 11(11), 3054–3067. https://doi.org/10.1039/C9SC04842A
  5. Hutcheon C, Paulvannan P, Subramanian N*. Cytoplasmic sensing in innate immunity. Encyclopedia of Cell Biology, edited by Ralph A. Bradshaw and Philip Stahl. Vol.3, Pages 710-726, 2016. ISBN: 978-0-12-394796-3.
  6. Rommereim L.M., Subramanian, N*. AIMing 2 Curtail Cancer. Cell. 162: 18-20, 2015.
  7. Subramanian N*, Torabi-Parizi P, Gottschalk RA, Germain RN, Dutta B*. Network representations of immune system complexity. Wiley Interdiscip Rev Syst Biol Med. Jan-Feb;7(1):13-38, 2015. *Corresponding authors
  8. Subramanian, N*., Natarajan, K., Clatworthy, M., Wang, Z., Germain, R.N*. The adapter MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell. 153: 348–361, 2013. *Corresponding authors.
  9. Lee, G.S., Subramanian, N., Kim, A., Aksentijevich, I., Goldbach-Mansky, R., Sacks, D.B., Germain, R.N., Kastner, D.L., Chae, J.J. The calcium sensing receptor controls NLRP3 inflammasome activation through intracellular Ca2+ and cAMP. Nature 492: 123-127, 2012.
  10. Kastenmuller, K., Torabi-Parizi, P., Subramanian, N., Laemmerman. T., Germain, R.N. A spatially organized multicellular innate immune response in lymph nodes limits systemic pathogen spread. Cell 150(6): 1235-1248, 2012.
  11. Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, Torabi-Parizi P, Subramanian N., Bunney TD, Baxendale RW, Martins MS, Romberg N, Komarow H, Aksentijevich I, Kim HS, Ho J, Cruse G, Jung MY, Gilfillan AM, Metcalfe DD, Nelson C, O’Brien M, Wisch L, Stone K, Douek DC, Gandhi C, Wanderer AA, Lee H, Nelson SF, Shianna KV, Cirulli ET, Goldstein DB, Long EO, Moir S, Meffre E, Holland SM, Kastner DL, Katan M, Hoffman HM, Milner JD. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med. 366(4): 330-338, 2012.
  12. Kastenmuller, W., Gasteiger, G., Subramanian, N., Sparwasser, T., Busch, D.H., Belkaid, Y., Drexler, I., Germain. R.N. Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2 restriction. J. Immunol. 187(6): 3186-3197, 2011.
  13. Subramanian, N., Qadri, A. Lysophospholipid sensing triggers secretion of flagellin from pathogenic Salmonella. Nature Immunol. 7: 583-589, 2006.
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