Liang, J, Huang, H-I, Benzatti, FP, Karlsson, AB, Zhang, JJ, Youssef, N, Ma, A, Hale, LP, and Hammer, GE. "Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88." Cell reports 17, no. 5 (October 2016): 1330-1343.
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 at Berkeley, 2006
Selected Grants and Awards
- 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
- Organization and Function of Cellular Structure
- Basic Immunology Training Program
- Microbiota induced upregulation of PDL1 on intestinal dendritic cells in intestinal tumorig
- Dendritic cell orchestration of colitogenic T cells in inflammatory bowel disease
Hammer, G, Liang, J, Huang, H-I, Benzatti, F, Karlsson, A, and Hale, LP. "Microbiota upregulate distinct APC functions in each intestinal dendritic cell subset, in a Myd88-independent fashion." May 1, 2016.
Callahan, JA, Hammer, GE, Agelides, A, Duong, BH, Oshima, S, North, J, Advincula, R, Shifrin, N, Truong, H-A, Paw, J, Barrera, J, DeFranco, A, Rosenblum, MD, Malynn, BA, and Ma, A. "Cutting edge: ABIN-1 protects against psoriasis by restricting MyD88 signals in dendritic cells." Journal of immunology (Baltimore, Md. : 1950) 191, no. 2 (July 2013): 535-539.
Lu, TT, Onizawa, M, Hammer, GE, Turer, EE, Yin, Q, Damko, E, Agelidis, A, Shifrin, N, Advincula, R, Barrera, J, Malynn, BA, Wu, H, and Ma, A. "Dimerization and ubiquitin mediated recruitment of A20, a complex deubiquitinating enzyme." Immunity 38, no. 5 (May 2013): 896-905.
Hammer, GE, and Ma, A. "Molecular control of steady-state dendritic cell maturation and immune homeostasis." Annual review of immunology 31 (January 17, 2013): 743-791. (Review)
Hammer, GE, Turer, EE, Taylor, KE, Fang, CJ, Advincula, R, Oshima, S, Barrera, J, Huang, EJ, Hou, B, Malynn, BA, Reizis, B, DeFranco, A, Criswell, LA, Nakamura, MC, and Ma, A. "Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis." Nature immunology 12, no. 12 (October 23, 2011): 1184-1193.
Hammer, GE, and Shastri, N. "Construction and destruction of MHC class I in the peptide-loading complex." Nature immunology 8, no. 8 (August 2007): 793-794.
Hammer, GE, Kanaseki, T, and Shastri, N. "The final touches make perfect the peptide-MHC class I repertoire." Immunity 26, no. 4 (April 2007): 397-406. (Review)
Hammer, GE, Gonzalez, F, James, E, Nolla, H, and Shastri, N. "In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides." Nature immunology 8, no. 1 (January 2007): 101-108.
Kanaseki, T, Blanchard, N, Hammer, GE, Gonzalez, F, and Shastri, N. "ERAAP synergizes with MHC class I molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum." Immunity 25, no. 5 (November 2006): 795-806.
Kanaseki, T, Blanchard, N, Hammer, GE, Gonzalez, F, and Shastri, N. "ERAAP and MHC class I molecules collaborate to generate the exact length of antigenic peptides in the endoplasmic reticulum." April 1, 2006.
Hammer, GE, Gonzalez, F, Champsaur, M, Cado, D, and Shastri, N. "The aminopeptidase ERAAP shapes the peptide repertoire displayed by major histocompatibility complex class I molecules." Nature immunology 7, no. 1 (January 2006): 103-112.
McMahon, CW, Zajac, AJ, Jamieson, AM, Corral, L, Hammer, GE, Ahmed, R, and Raulet, DH. "Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells." Journal of immunology (Baltimore, Md. : 1950) 169, no. 3 (August 2002): 1444-1452.