Gianna Hammer

Overview:

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.

Positions:

Assistant Professor of Immunology

Immunology
School of Medicine

Assistant Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2006

University of California at Berkeley

Grants:

Role of osteopontin in innate immunity during infections and inflammation

Administered By
Immunology
Awarded By
National Institutes of Health
Role
Collaborator
Start Date
End Date

SALMONELLA HIJACKING OF STAT3 AND CONSEQUENCES FOR DISEASE

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

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

Administered By
Immunology
Awarded By
Pew Charitable Trusts
Role
Principal Investigator
Start Date
End Date

Dendritic cells in colorectal cancer

Administered By
Immunology
Awarded By
American Association of Immunologists
Role
Principal Investigator
Start Date
End Date

Microbiota induced upregulation of PDL1 on intestinal dendritic cells in intestinal tumorig

Administered By
Immunology
Awarded By
V Foundation for Cancer Research
Role
Principal Investigator
Start Date
End Date

Publications:

Opportunities and Challenges for Single-Unit Recordings from Enteric Neurons in Awake Animals.

Advanced electrode designs have made single-unit neural recordings commonplace in modern neuroscience research. However, single-unit resolution remains out of reach for the intrinsic neurons of the gastrointestinal system. Single-unit recordings of the enteric (gut) nervous system have been conducted in anesthetized animal models and excised tissue, but there is a large physiological gap between awake and anesthetized animals, particularly for the enteric nervous system. Here, we describe the opportunity for advancing enteric neuroscience offered by single-unit recording capabilities in awake animals. We highlight the primary challenges to microelectrodes in the gastrointestinal system including structural, physiological, and signal quality challenges, and we provide design criteria recommendations for enteric microelectrodes.
Authors
Barth, BB; Huang, H-I; Hammer, GE; Shen, X
MLA Citation
Barth, Bradley B., et al. “Opportunities and Challenges for Single-Unit Recordings from Enteric Neurons in Awake Animals..” Micromachines (Basel), vol. 9, no. 9, Aug. 2018. Pubmed, doi:10.3390/mi9090428.
URI
https://scholars.duke.edu/individual/pub1357891
PMID
30424361
Source
pubmed
Published In
Micromachines
Volume
9
Published Date
DOI
10.3390/mi9090428

Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells.

NK cells express several families of receptors that play central roles in target cell recognition. These NK cell receptors are also expressed by certain memory phenotype CD8(+) T cells, and in some cases are up-regulated in T cells responding to viral infection. To determine how the profile of NK receptor expression changes in murine CD8(+) T cells as they respond to intracellular pathogens, we used class I tetramer reagents to directly examine Ag-specific T cells during lymphocytic choriomeningitis virus and Listeria monocytogenes infections. We found that the majority of pathogen-specific CD8(+) T cells initiated expression of the inhibitory CD94/NKG2A heterodimer, the KLRG1 receptor, and a novel murine NK cell marker (10D7); conversely, very few Ag-specific T cells expressed Ly49 family members. The up-regulation of these receptors was independent of IL-15 and persisted long after clearance of the pathogen. The expression of CD94/NKG2A was rapidly initiated in naive CD8(+) T cells responding to peptide Ags in vitro and on many of the naive T cells that proliferate when transferred into lymphopenic (Rag-1(-/-)) hosts. Thus, CD94/NKG2A expression is a common consequence of CD8(+) T cell activation. Binding of the CD94/NKG2A receptor by its ligand (Qa-1(b)) did not significantly inhibit CD8(+) T cell effector functions. However, expression of CD94 and NKG2A transgenes partially inhibited early events of T cell activation. These subtle effects suggest that CD94/NKG2A-mediated inhibition of T cells may be limited to particular circumstances or may synergize with other receptors that are similarly up-regulated.
Authors
McMahon, CW; Zajac, AJ; Jamieson, AM; Corral, L; Hammer, GE; Ahmed, R; Raulet, DH
MLA Citation
McMahon, Christopher W., et al. “Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8(+) T cells..” J Immunol, vol. 169, no. 3, Aug. 2002, pp. 1444–52. Pubmed, doi:10.4049/jimmunol.169.3.1444.
URI
https://scholars.duke.edu/individual/pub1006593
PMID
12133970
Source
pubmed
Published In
The Journal of Immunology
Volume
169
Published Date
Start Page
1444
End Page
1452
DOI
10.4049/jimmunol.169.3.1444

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.

Salmonella enterica is an important foodborne pathogen that uses secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. enterica serovars cause disease syndromes ranging from gastroenteritis to typhoid fever and vary in their effector repertoire. We leveraged this natural diversity to identify stm2585, here designated sarA (Salmonella anti-inflammatory response activator), as a Salmonella effector that induces production of the anti-inflammatory cytokine IL-10. RNA-seq of cells infected with either ΔsarA or wild-type S. Typhimurium revealed that SarA activates STAT3 transcriptional targets. Consistent with this, SarA is necessary and sufficient for STAT3 phosphorylation, STAT3 inhibition blocks IL-10 production, and SarA and STAT3 interact by co-immunoprecipitation. These effects of SarA contribute to intracellular replication in vitro and bacterial load at systemic sites in mice. Our results demonstrate the power of using comparative genomics for identifying effectors and that Salmonella has evolved mechanisms for activating an important anti-inflammatory pathway.
Authors
Jaslow, SL; Gibbs, KD; Fricke, WF; Wang, L; Pittman, KJ; Mammel, MK; Thaden, JT; Fowler, VG; Hammer, GE; Elfenbein, JR; Ko, DC
MLA Citation
Jaslow, Sarah L., et al. “Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10..” Cell Rep, vol. 23, no. 12, June 2018, pp. 3525–36. Pubmed, doi:10.1016/j.celrep.2018.05.072.
URI
https://scholars.duke.edu/individual/pub1325026
PMID
29924996
Source
pubmed
Published In
Cell Reports
Volume
23
Published Date
Start Page
3525
End Page
3536
DOI
10.1016/j.celrep.2018.05.072

609 IL-27 signaling is essential for IL-15 production and mediates contact hypersensitivity

Authors
Pontius, L; Suwanpradid, J; Kwock, J; Yang, B; Maycock, J; Kedl, R; Hammer, G; MacLeod, AS
MLA Citation
Pontius, L., et al. “609 IL-27 signaling is essential for IL-15 production and mediates contact hypersensitivity.” Journal of Investigative Dermatology, vol. 137, no. 5, Elsevier BV, 2017, pp. S105–S105. Crossref, doi:10.1016/j.jid.2017.02.631.
URI
https://scholars.duke.edu/individual/pub1269638
Source
crossref
Published In
Journal of Investigative Dermatology
Volume
137
Published Date
Start Page
S105
End Page
S105
DOI
10.1016/j.jid.2017.02.631

Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88.

Normal dynamics between microbiota and dendritic cells (DCs) support modest numbers of T cells, yet these do not cause inflammation. The DCs that induce inflammatory T cells and the signals that drive this process remain unclear. Here, we demonstrate that small intestine DCs lacking the signaling attenuator A20 induce inflammatory T cells and that the signals perceived and antigen-presenting cell (APC) functions are unique for different DC subsets. Thus, although CD103+CD11b- DCs exclusively instruct IFNγ+ T cells, CD103+CD11b+ DCs exclusively instruct IL-17+ T cells. Surprisingly, APC functions of both DC subsets are upregulated in a MyD88-independent fashion. In contrast, CD103-CD11b+ DCs instruct both IFNγ+ and IL-17+ T cells, and only the IL-17-inducing APC functions require MyD88. In disease pathogenesis, both CD103-CD11b+ and CD103+CD11b+ DCs expand pathologic Th17 cells. Thus, in disease pathogenesis, specific DCs instruct specific inflammatory T cells.
Authors
Liang, J; Huang, H-I; Benzatti, FP; Karlsson, AB; Zhang, JJ; Youssef, N; Ma, A; Hale, LP; Hammer, GE
MLA Citation
Liang, Jie, et al. “Inflammatory Th1 and Th17 in the Intestine Are Each Driven by Functionally Specialized Dendritic Cells with Distinct Requirements for MyD88..” Cell Rep, vol. 17, no. 5, Oct. 2016, pp. 1330–43. Pubmed, doi:10.1016/j.celrep.2016.09.091.
URI
https://scholars.duke.edu/individual/pub1150515
PMID
27783947
Source
pubmed
Published In
Cell Reports
Volume
17
Published Date
Start Page
1330
End Page
1343
DOI
10.1016/j.celrep.2016.09.091