Liang, Jie, Junyi J. Zhang, Hsin-I Huang, Masashi Kanayama, Nourhan Youssef, Yingai J. Jin, Estefany Y. Reyes, et al. “The Ubiquitin-Modifying Enzyme A20 Terminates C-Type Lectin Receptor Signals and Is a Suppressor of Host Defense against Systemic Fungal Infection.” Infect Immun 88, no. 9 (August 19, 2020). https://doi.org/10.1128/IAI.00048-20.
Gianna Hammer, PhD
The study of microbial communities that reside on and within the human body (the microbiome) is considered one of the hottest areas of science today. It is now well appreciated that the microbiome has remarkable influence on diverse aspects of human health and disease. To understand how the microbiome exerts such influence, our lab seeks to define the mechanisms by which cells of the immune system interact with microbes that reside in the intestine. To the immune system, co-existence with microbes is a remarkable paradox: while immune cells are skilled operatives fixated on eliminating microbial invaders, these same cells are somehow restrained from attacking microbial commensals. This restraint is critical to prevent inflammatory bowel disease (IBD).
Our research seeks to understand the pathogenesis of inflammatory bowel disease, and understand interactions between host and the microbiome. In particular, we study the roles of dendritic cells. Dendritic cells are exquisitely sensitive to microbes, and after engaging microbes or microbial products, dendritic cells are reprogrammed into inflammatory cells with potent ability to activate other immune cells. Because of their potent influence over the immune system, dendritic cells are in a prime position to relay signals from the microbiome, and we have found that dendritic cells are key players in pathogenesis of inflammatory bowel disease. To prevent IBD, dendritic cells require the NF-kB suppressor, A20. A20 suppresses multiple disease-associated signaling pathways, including TNF, NOD2 and Toll-like receptors. Using biochemistry and in vivo analyses, we are interrogating the roles of these receptors and signaling pathways in regulating the responses of dendritic cells to the intestinal microbiome. Additionally, we seek to identify new signaling pathways by which DCs interact with microbial communities of the intestine.
Education and Training
- Ph.D., University of California - Berkeley, 2006
Selected Grants and Awards
- Decoding T cell-mediated mechanisms underpinning immunity without adverse pathology at mucosal barriers
- Cell and Molecular Biology Training Program
- Basic Immunology Training Program
- Role of IRGM proteins in immunity to enteric bacteria
- APCs and environmental cues for inflammation-linked Th17 immunity
- SALMONELLA HIJACKING OF STAT3 AND CONSEQUENCES FOR DISEASE
- Role of osteopontin in innate immunity during infections and inflammation
- Effects of storage method on intestinal allograft immune profile and viability
- Role of Dendritic Cell-mediated T Cell Activation in Salt-sensitive Hypertension
- Organization and Function of Cellular Structure
- Identification of anti-commensal T cells, their pathological function, and their commensal antigen specificities in inflammatory bowel disease using a novel in vivo reporter system
- Dendritic cells in colorectal cancer
- IL-27 in skin host defense and regeneration
- Microbiota induced upregulation of PDL1 on intestinal dendritic cells in intestinal tumorig
- The role of dendritic cell-mediated T cell activation in hypertension
- Dendritic cell orchestration of colitogenic T cells in inflammatory bowel disease
Taylor, Gregory A., Hsin-I Huang, Brian E. Fee, Nourhan Youssef, Mark L. Jewell, Viviana Cantillana, Alexi A. Schoenborn, et al. “Irgm1-deficiency leads to myeloid dysfunction in colon lamina propria and susceptibility to the intestinal pathogen Citrobacter rodentium.” Plos Pathog 16, no. 5 (May 2020): e1008553. https://doi.org/10.1371/journal.ppat.1008553.
Wen, Yi, Nathan P. Rudemiller, Jiandong Zhang, Xiaohan Lu, Jiafa Ren, Jamie R. Privratsky, Robert Griffiths, Junyi J. Zhang, Gianna E. Hammer, and Steven D. Crowley. “C-C Motif Chemokine Receptor 7 Exacerbates Hypertension Through Effects on T Lymphocyte Trafficking.” Hypertension 75, no. 3 (March 2020): 869–76. https://doi.org/10.1161/HYPERTENSIONAHA.119.14148.
Lu, Xiaohan, Nathan P. Rudemiller, Yi Wen, Jiafa Ren, Gianna E. Hammer, Robert Griffiths, Jamie R. Privratsky, Bo Yang, Matthew A. Sparks, and Steven D. Crowley. “A20 in Myeloid Cells Protects Against Hypertension by Inhibiting Dendritic Cell-Mediated T-Cell Activation.” Circ Res 125, no. 12 (December 6, 2019): 1055–66. https://doi.org/10.1161/CIRCRESAHA.119.315343.
Huang, Hsin-I, and Gianna Hammer. “Paradoxical pro-tumor functions of dendritic cells on colorectal cancer.” In Journal of Immunology, Vol. 202. AMER ASSOC IMMUNOLOGISTS, 2019.
Jaslow, Sarah L., Kyle D. Gibbs, W Florian Fricke, Liuyang Wang, Kelly J. Pittman, Mark K. Mammel, Joshua T. Thaden, et al. “Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.” Cell Rep 23, no. 12 (June 19, 2018): 3525–36. https://doi.org/10.1016/j.celrep.2018.05.072.
Liang, Jie, Hsin-I Huang, Fernanda P. Benzatti, Amelia B. Karlsson, Junyi J. Zhang, Nourhan Youssef, Averil Ma, Laura P. Hale, and Gianna E. Hammer. “Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88.” Cell Rep 17, no. 5 (October 25, 2016): 1330–43. https://doi.org/10.1016/j.celrep.2016.09.091.
Hammer, Gianna, Jie Liang, Hsin-I Huang, Fernanda Benzatti, Amelia Karlsson, and Laura P. Hale. “Microbiota upregulate distinct APC functions in each intestinal dendritic cell subset, in a Myd88-independent fashion.” In Journal of Immunology, Vol. 196. AMER ASSOC IMMUNOLOGISTS, 2016.
Callahan, Joseph A., Gianna E. Hammer, Alexander Agelides, Bao H. Duong, Shigeru Oshima, Jeffrey North, Rommel Advincula, et al. “Cutting edge: ABIN-1 protects against psoriasis by restricting MyD88 signals in dendritic cells.” J Immunol 191, no. 2 (July 15, 2013): 535–39. https://doi.org/10.4049/jimmunol.1203335.
Lu, Timothy T., Michio Onizawa, Gianna E. Hammer, Emre E. Turer, Qian Yin, Ermelinda Damko, Alexander Agelidis, et al. “Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme.” Immunity 38, no. 5 (May 23, 2013): 896–905. https://doi.org/10.1016/j.immuni.2013.03.008.
Hammer, Gianna Elena, and Averil Ma. “Molecular control of steady-state dendritic cell maturation and immune homeostasis.” Annu Rev Immunol 31 (2013): 743–91. https://doi.org/10.1146/annurev-immunol-020711-074929.
Hammer, Gianna Elena, Emre E. Turer, Kimberly E. Taylor, Celia J. Fang, Rommel Advincula, Shigeru Oshima, Julio Barrera, et al. “Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.” Nat Immunol 12, no. 12 (October 23, 2011): 1184–93. https://doi.org/10.1038/ni.2135.