Immunology Faculty Member - Isaac Chiu, PhD

Isaac Chiu, PhD

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



Our lab investigates the role of neural-immune interactions at major barrier tissues including the gut, skin, and respiratory tract. We aim to define how neural circuits actively participate in host defense against pathogens and inflammatory diseases.

Neural-immune interactions in host defense and immunity
It is increasingly clear that the nervous system plays a powerful role in regulating the immune system during inflammation. We recently found that sensory neurons play a key role in regulating bacterial host defense. Sensory neurons release neuropeptides such as CGRP, SP, or VIP which act on their cognate receptors on immune cells to modulate immune function. Sympathetic neurons release norepinephrine which acts on adrenergic receptors expressed by immune cells. We are now investigating the role of these neuro-immune interactions in the skin, gut, and respiratory tract. We aim to use targeted genetic and pharmacological tools to ascertain the role of these neuro-immune interactions in host defense against pathogens and in tissue inflammation.

Neural-immune interactions in pain and itch
Nociceptor neurons and pruriceptor neurons are the specific subsets of sensory neurons that produce pain and itch, respectively. The mechanisms leading to chronic pain or itch are not well understood. neurons express receptors for specific immune derived factors, including interleukins and lipid mediators. We are investigating how specific immune signaling mechanisms may drive chronic itch or chronic pain.

Neuronal sensing of bacterial pathogens and the microbiota
Pain is a component of many infectious diseases, including bacterial and viral infection. We have found that nociceptor sensory neurons are directly activated by bacterial pathogens and their secreted factors produce pain. We have found that different types of gut-commensal microbes are able to directly induce calcium influx in DRG sensory neurons. The gut-brain-axis could be involved in regulating pain. We are identifying the key molecular mechanisms by which different types of microbes and pathogens induce neuronal activation. Isolation of microbe-derived neuromodulatory factors could lead to new treatments for chronic pain and infectious diseases.



Last Update: 6/18/2018



Publications

Pinho-Ribeiro FA, Baddal B, Haarsma R, O’Seaghdha M, Yang NJ, Blake KJ, Portley M, Verri Jr. WA, Dale JB, Wessels MR, and Chiu IM (2018). Blocking neuronal signaling to immune cells treats streptococcal invasive infection. Cell. May 17;173(5):1083-1097. PMID: 29754819.

Baral P, Umans BD, Li Lu, Wallrapp A, Bist M, Kirschbaum T, Wei Y, Zhou Y, Kuchroo VK, Burkett PR, Yipp BG, Liberles SD, and
Chiu IM (2018). Nociceptor sensory neurons suppress neutrophil and gd T cell responses in bacterial lung infections and lethal pneumonia. Nature Medicine. 2018 Mar 5. PMID: 29505031.

Blake KJ, Baral P, Voisin T, Lubkin A, Pinho-Ribeiro FA, Adams KL, Roberson DP, Ma YC, Otto M, Woolf CJ, Torres VJ, and
Chiu IM (2018). Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314. Nature Communications. 2018 Jan 2; 9:37. PMCID: PMC5750211.

Yissachar N, Zhou Y, Ung L, Lai NY, Mohan JF, Ehrlicher A, Weitz DA, Kasper D,
Chiu IM*, Mathis D*, and Benoist C* (2017). An intestinal organ culture system uncovers a role for the nervous system in microbe/immunocyte crosstalk. Cell. 2017 Mar 9; 168(6):1135-1148. PMCID: PMC5396461. *Co-corresponding authors.

Wallrapp A*, Riesenfeld SJ*, Burkett PR*, Abdulnour RE, Nyman J, Dionne D, Hofree M, Cuoco MS, Rodman C, Farouq D, Haas BJ, Tickle TL, Trombetta JJ, Baral P, Klose CSN, Mahlakoiv T, Artis D, Rozenblatt-Rosen O,
Chiu IM, Levy BD, Kowalczyk MS, Regev A, and Kuchroo VK (2017). The neuropeptide NMU amplifies ILC2-driven allergic lung inflammation. Nature. 2017 Sep 13. PMID: 28902842.

Chiu IM*, Barrett LB, Williams EK, Strochlic DE, Weyer AD, Lou S, Bryman G, Roberson DP, Ghasemlou N, Piccoli C, Ahat E, Wang V, Cobos EJ, Stucky CL, Ma Q, Liberles SD, and Woolf CJ* (2014). Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity. ELife. 2014 Dec 19;3. PMID: 25525749. *Co-corresponding authors.

Chiu IM, Morimoto ET, Goodarzi H, Liao JT, O’Keefe S, Phatnani HP, Carroll MC, Levy, S, Tavazoie S, Myers RM, and Maniatis T (2013). A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model. Cell Reports. 2013 Jul 25; 4(2):385-401. PMCID: PMC4272581.

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 (2013). Bacteria activate sensory neurons that modulate pain and inflammation. Nature. 2013 Sep 5; 501(7465): 52-7. PMCID: PMC3773968.



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