You are here

Gregory Sempowski

Associate Professor, Human Vaccine Institute
Pathology
(919) 684-4386
Research Interest: 
Immunology
Microbiology and virology
Research Summary: 
The Duke Human Vaccine Institute Laboratory of T-Cell Biology and Immune Reconstitution is located in the Regional Biocontainment Building at Duke. The Sempowski lab has an NIH-funded program to study immune senescence associated with aging, and has developed novel approaches to monitoring host response to infectious agents and/or vaccination (e.g multiplex biomarker profiling and in vivo imaging).
Research Description: 

Immune Senescence and T Cell Reconstitution
The Sempowski lab is primarily focused on developing strategies to enhance T cell reconstitution in order to offset thymic immune depletion due to immunodeficiency associated with aging, stress, or illness. The thymus plays an important role in maintaining the peripheral T cell pool in children and adults. As the thymus gets smaller with age, it produces significantly lower amounts of T cells resulting in an overall reduced immune response in older individuals. Currently, there are no treatments available to protect against aging, stress or illness-related thymic atrophy or accelerate recovery, thus leaving the immune system compromised.

The Sempowski group is working to define the mechanisms that drive thymic involution and find ways of blocking or reversing thymic involution in order to enhance host response in at-risk populations against potential natural or man-made biothreats. The lab has identified the IL-6 cytokine gene family (i.e., leukemia inhibitory factor, IL-6, and oncostatin M) as thymosuppressive agents by the observation that they can acutely involute the thymus when injected into a young, healthy mouse. They also have identified leptin as a novel, thymostimulatory agent that can protect against stress-induced acute thymic atrophy. Identified hormones, cytokines and inhibitors of cytokine receptors are being tested as possible strategies to stimulate thymopoiesis and T cell reconstitution in mouse models of vaccination and infectious challenge.

Effects of Radiation and Aging on the Human Immune System
The Sempowski lab is part of an international consortium of nine labs funded by NIAID to study the effects of atomic bomb radiation and aging on the human immune system. Investigators in both the United States and Japan are systematically analyzing biological samples from the unique population of elderly Japanese atomic bomb survivors to better understand the health consequences of exposure to ionizing radiation on the natural aging process.

Shared Resource Facilities
The Sempowski laboratory contains a service component consisting of the Immune Reconstitution & Biomarker Analysis Shared Resource and the Biocontainment Animal Imaging Shared Resource. These facilities are supported by three NIH-funded programs.

SE STI CRC - Immunology Core
The Southeast Sexually Transmitted Infection Cooperative Research Center (SE STI CRC) based at UNC Chapel Hill supports an Immunology Core that provides expertise in systemic and mucosal immunity with an emphasis on humoral, cellular and biomarker analysis. This new component of the center in 2009 was included to provide mechanistic study of innate and adaptive immune response to N. gonorrhoeae or experimental vaccination for N. gonorrhoeae.

SERCEB - Flow, Biomarker and Imaging Core
The Southeast Regional Center of Excellence for Emerging Infections and Biodefense (SERCEB) supports a BSL3 Host Pathogen Interaction Core (FBI Core). This Core is comprised of technologies and services offered through the NIAID-funded Regional Biocontainment Laboratory at Duke in conjunction with DHVI shared resource facilities. This BSL3 SERCEB Core routinely provides investigators with high-quality flow cytometry, in vivo imaging, protein array analysis, and complete blood count/hematologic analysis for their basic and applied biodefense and emerging infectious disease research efforts.

RadCCORE - Immune Monitoring Core
The Radiation Countermeasures Center of Research Excellence (RadCCORE) based at Duke supports an Immune Monitoring Core comprised of technologies and services offered by two service laboratories within the Duke Human Vaccine Institute (DHVI): the Flow Cytometry Facility and the Immune Reconstitution and Biomarker Facility. The Immune Monitoring Core centrally provides RadCCORE investigators with high quality, state-of-the-art cell sorting, multiplex cytokine/chemokine assays, and T cell receptor gene expression analysis for their basic and applied research efforts.

Publications: 
Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses.
Billard MJ, Gruver AL, Sempowski GD.
PLoS One. 2011. 6:e17940.

Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.
Cain DW, Snowden PB, Sempowski GD, Kelsoe G.
PLoS One. 2011. 6:e19957.

Two genes on A/J chromosome 18 are associated with susceptibility to Staphylococcus aureus infection by combined microarray and QTL analyses.
Ahn SH, Deshmukh H, Johnson N, Cowell LG, Rude TH, Scott WK, Nelson CL, Zaas AK, Marchuk DA, Keum S, Lamlertthon S, Sharma-Kuinkel BK, Sempowski GD, Fowler VG.
PLoS Pathog. 2010. 6:e1001088.

Leptin receptor is expressed in thymus medulla and leptin protects against thymic remodeling during endotoxemia-induced thymus involution.
Gruver AL, Ventevogel MS, Sempowski GD.
J Endocrinol. 2009. 203:75-85.

Thymopoietic and bone marrow response to murine Pneumocystis pneumonia.
Shi X, Zhang P, Sempowski GD, Shellito JE.
Infect Immun. 2011. 79:2031-42.