BBS Faculty Member - Isaac Chiu

Isaac Chiu

Department of Microbiology and Immunobiology

Harvard Medical School
NRB Building, Room 830
77 Avenue Louis Pasteur
Boston, MA 02115
Email: isaac_chiu@hms.harvard.edu



Our goal is to understand the role of the nervous system in host defense and inflammation. Nociceptor neurons protect the organism from danger by detecting potentially harmful/noxious stimuli and eliciting the sensation of pain or itch. Celsus defined pain as one of the cardinal signs of inflammation; however, the molecular mechanisms of pain during inflammation are not well understood. We found that nociceptors express specific receptors for pathogen and immune-derived factors, and play a role in modulating immune cell function.

Pathogenic mechanisms of pain
Pain is a component of many infectious diseases, including bacterial and viral infection. We have found that Staphylococcus aureus produces pain by directly activating neurons through N-formylated peptides and the pore-forming toxin alpha-hemolysin. Identifying how pathogens induce nociceptor activation and targeting these mechanisms could be important in the treatment of pain and inflammation.

Somatosensory neuron subsets in inflammation
Nociceptors encode the detection of different sensory modalities including heat and mechanical sensitivity at the molecular level. Similar specification may also mediate different inflammatory conditions. For example, bacterial infection often causes pain, whereas allergic inflammation induces itch. We will use electrophysiology, molecular biology, and animal models to investigate neuronal subsets involved in detection of pathogenic and inflammatory stimuli.

Neuro-immune cross-talk in host defense
Molecular cross-talk between the nervous system and immune system is involved in inflammatory responses. We found that nociceptor-derived neuropeptides alter innate immune cell recruitment and lymph node hypertrophy during infection. We aim to understand the molecular mechanisms by which neurons affect the generation of innate and adaptive immune responses during host defense.



Last Update: 7/14/2014



Publications

For a complete listing of publications click here.

 


 

Chiu IM, Heesters B, Ghasemlou N, Von Hehn CA, Zhao F, Tran J, Wainger BW, Strominger A, Muralidharan S, Horswill A, Bubeck-Wardenburg JA, Carroll MC, Hwang SW, and Woolf CJ. Bacteria activate sensory neurons that modulate pain and inflammation. Nature 2013 Sep 5; 501(7465):52-7. PMID: 23965627

Chiu IM, Morimoto ET, Goodarzi H, Liao JT, O’Keefe S, Phatnani HP, Carroll MC, Levy, S, Tavazoie S, Myers RM, and Maniatis T. A neurodegeneration-specific gene-expression signature and immune profile of acutely isolated microglia from an ALS mouse model.
Cell Reports 2013 Jul 25; 4(2): 385-401. PMID: 23850290

Chiu IM*, Von Hehn CA*, and Woolf CJ. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology.
Nature Neuroscience 2012 Jul 26;15(8): 1063-7. *These authors contributed equally. PMID: 22837035

Kim SS, Ye C, Kumar P, Chiu I, Subramanya S, Wu H, Shankar P, and Manjunath N. Targeted delivery of siRNA to macrophages for anti-inflammatory treatment.
Molecular Therapy 2010 May; 18(5): 993-1001. PMID: 20216529

Chiu IM, Phatnani H, Kuligowski M, Tapia JC, Carrasco MA, Zhang M, Maniatis T, and Carroll MC. Activation of innate and humoral immunity in the peripheral nervous system of ALS transgenic mice.
PNAS 2009 Dec 8; 106(49): 20960-20965. PMID: 19933335

Chiu IM, Chen A, Zheng Y, Kosaras B, Tsiftsoglou SA, Vartanian TK, Brown RH Jr, and Carroll MC. T lymphocytes potentiate endogenous neuro-protective inflammation in a mouse model of ALS.
PNAS 2008 Nov 18; 106(46): 17913-17918. PMID: 18997009



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