The Zhang Lab

Hailong Zhang, Ph.D.
Hailong Zhang, Ph.D.
Assistant Professor
College of Medicine
Department of Pharmacology and Immunology

Education
2010-2015, Ph.D., Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Chinese Academy of Sciences (CAS)

2016-2024 Postdoctoral Fellow/Instructor, Howard Hughes Medical Institute (HHMI), Harvard Medical School (HMS)

Contact Information
Email: zhangha@musc.edu
Telephone: 843-876-2838
Office: BSB 319D

Lab Webpage
www.hailongzhanglab.com

Academic Focus
Enteric Nervous System
Host-Pathogen Interaction
Infection, Inflammation and Cancer

Research Interests

Zhang Lab Research Interests

Figure 1

At the Zhang Lab, we investigate the interactions between the host, microbiota/pathogens in the intestine, with a primary focus on the enteric nervous system (ENS) and its crucial role in defending against infections and regulating inflammation. The ENS is not only localized in the myenteric plexus, but its cell bodies and projections extend into the lamina propria and each villus (Fig 1). Despite being the second-largest nervous system in the body, the ENS is significantly understudied compared to the central nervous system. Nevertheless, it plays crucial roles in sensing microbiota, defending against pathogenic infections, maintaining immune homeostasis, regulating epithelial cell functions, and even influencing social behaviors.

Our ongoing projects leverage multiple conditional knockout mouse strains to study how specific enteric neuronal circuits regulate immune and epithelial cell function. For instance, our previous work uncovered a novel neuron-immune axis in which specific enteric serotonergic neuronal circuits support the gut homing, retention, and activation of plasmacytoid dendritic cells (pDC) via serotonin-HTR7 signaling. This mechanism plays a crucial role in regulating intestinal IgA B cell differentiation and mucosal defense (Fig. 2). Furthermore, we found that these circuits are important for anxiety behaviors. We are now focusing on further investigating the role of these enteric serotonergic circuits in inflammation and colon cancer development.

Zhang Lab Figure 2

Figure 2

Recent Publications

Enteric neurons

1.     H Zhang, Y Hasegawa, DR. Leitner, T Zhang, M Suzuki, RP. Jackson, MK. Waldor. Enteric neurons control intestinal plasmacytoid DC function via 5-HT-HTR7 signaling (Nature Communications)

2.     H Zhang, DR. Leitner, Y Hasegawa, MK. Waldor. Peripheral serotonergic neurons regulate gut motility and anxiety-like behavior. Curr Biol 34, R133-R134 (2024)

Host-pathogen interactions

3.     M.T. White, H Zhang, U Eckhard, K Hullahalli, S Wu, J Queen, F. X Gomis-Ruth, M. K. Waldor, C. L. Sears. A procarcinogenic bacterial metalloprotease binds claudin-4 to mediate toxicity on colonic epithelial cells (Under revision in Nature)

4.     K Hullahalli, KG. Dailey, Y Hasegawa, M Suzuki, H Zhang, DW. Threadgill, MK. Waldor. Genetic and immune determinants of E. coli liver abscess formation. Proc. NatI. Acad Sci USA 120, e2310053120 (2023)

5.     A Zoued, H Zhang, T Zhang, R Giorgio, CJ Kuehl, B Fakoya, B Sit, MK Waldor. Proteomic analysis of the host-pathogen interface in experimental cholera. Nat Chem biol (2021) 17 (11), 1199-1208.

6.     H Zhang, A Zoued, X Liu, B Sit, MK Waldor. Type I interferon remodels lysosome function and modifies intestinal epithelial defense. Proc. NatI. Acad Sci USA (2020) 117 (47), 29862-29871.

7.     JD D’Gama, Z Ma, H Zhang, X Liu, H Fan, ERA Morris, ND Cohen, CC Bentley, GB Pier, MK Waldor. A conserved streptococcal virulence regulator controls the expression of a distinct class of M-like proteins. mBio (2019) 10 (5), e02500-19.

 

Integrin & intestinal inflammation, Cancer

8.     Y Zhang*, R Xie*, H Zhang*, Y Zheng, C Lin, L Yang, M Huang, M Li, F Song, L Ling, M Yang, Y Liu, Q Wei, J Li, J Chen. Integrin β7 inhibits colorectal cancer pathogenesis via maintaining antitumor immunity. Cancer Immunol Res (2021) 9 (8): 967–980.

9.     H Zhang, Y Zheng, Y Pan, C Lin, S Wang, Z Yan, L Lu, G Ge, J Li, Y Zheng, J Chen. A mutation that blocks integrin α4β7 activation prevents adaptive immune-mediated colitis without increasing susceptibility to innate colitis. BMC Biology (2020) 18 (1), 1-15.

10.   H Liu, X Dai, X Cao, H Yan, X Ji, H Zhang, S Shen, Y Si, H Zhang, J Chen, L Li, JC Zhao, J Yu, X Feng, B Zhao. PRDM 4 mediates YAP‐induced cell invasion by activating leukocyte‐specific integrin β2 expression. EMBO reports (2018) 19 (6), e45180.

11.   Y Zhang, Y Pan, C Lin, Y Zheng, H Sun, H Zhang, J Wang, M Yuan, T Duan, Q Du, J Chen. Bile acids evoke placental inflammation by activating Gpbar1/NF-κB pathway in intrahepatic cholestasis of pregnancy. J. Mol. Cell Biol. (2016) 8 (6), 530-541.

12.   H Zhang, L Lu, Y Zheng, M Yuan, J Chen. Regulation of immune cell adhesion and migration by cell microenvironments. Life Science (2016) 28(2):239-247

13.   H Zhang, Y Zheng, Y Pan, C Xie, H Sun, Y Zhang, M Yuan, B Song, J Chen. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity. Mucosal immunology (2016) 9 (2), 391-400.

14.   Q Du, Y Pan, Y Zhang, H Zhang, Y Zheng, L Lu, J Wang, T Duan, J Chen. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation. BMC Med. Genet (2014) 7 (1), 1-11.