Gregory David Sempowski

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Professor in Medicine
Department / Division:
Medicine / Medicine - DHVI Faculty
Address:
909 S. Lasalle St
Rm 1005 Global Health Research Building,
Durham, NC 27705
Office Telephone:
(919) 684-4386
Research Interests:
The Laboratory of T-Cell Biology and Immune Reconstitution is led by Gregory D. Sempowski, PhD and is located in the Regional Biocontainment Building at Duke. The Sempowski lab has an independent research program studying immune senescence associated with aging and works collaboratively with investigators from Duke, UNC Chapel Hill, Memorial Sloan Kettering, University of Georgia, University of Arizona and the Radiation Effect Research Foundation (Hiroshima, Japan). The Laboratory of T-Cell Biology and Immune Reconstitution is also home to two DHVI Shared Resource Facilities which are supported by NIAID Core grants.

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.

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

Shared Resource Facilities
Lastly, the Sempowski laboratory contains a service component consisting of the Immune Reconstitution & Biomarker Analysis Shared Resource and the Biocontainment Animal Imaging Shared Resource. The IR & Biomarker Analysis facility provides access to specialized instrumentation for Real-Time qPCR and Luminex bead-based multiplex assays, and runs molecular assays to monitor thymic output in mouse, human and non-human primate samples. This facility provides the patented Mouse TREC Assay, which is performed regularly for investigators from all over the world. This assay has proven
Representative Publications:
  • Brickey, WJ; Neuringer, IP; Walton, W; Hua, X; Wang, EY; Jha, S; Sempowski, GD; Yang, X; Kirby, SL; Tilley, SL; Ting, JP. MyD88 provides a protective role in long-term radiation-induced lung injury. International Journal of Radiation Biology. 2012;88:335-347.  Abstract
  • Chinn, IK; Blackburn, CC; Manley, NR; Sempowski, GD. Changes in primary lymphoid organs with aging. Seminars in Immunology. 2012;24:309-320.  Abstract
  • Gonzalez, RJ; Weening, EH; Frothingham, R; Sempowski, GD; Miller, VL. Bioluminescence imaging to track bacterial dissemination of Yersinia pestis using different routes of infection in mice. BMC Microbiology. 2012;12:147.  Abstract
  • Kanda, J; Chiou, LW; Szabolcs, P; Sempowski, GD; Rizzieri, DA; Long, GD; Sullivan, KM; Gasparetto, C; Chute, JP; Morris, A; McPherson, J; Hale, J; Livingston, JA; Broadwater, G; Niedzwiecki, D; Chao, NJ; Horwitz, ME. Immune recovery in adult patients after myeloablative dual umbilical cord blood, matched sibling, and matched unrelated donor hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation. 2012;18:1664-1676.e1.  Abstract
  • Mendoza, AE; Neely, CJ; Charles, AG; Kartchner, LB; Brickey, WJ; Khoury, AL; Sempowski, GD; Ting, JP; Cairns, BA; Maile, R. Radiation combined with thermal injury induces immature myeloid cells. Shock. 2012;38:532-542.  Abstract
  • Thompson, AL; Johnson, BT; Sempowski, GD; Gunn, MD; Hou, B; DeFranco, AL; Staats, HF. Maximal adjuvant activity of nasally delivered IL-1¿ requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production. Journal of Immunology. 2012;188:2834-2846.  Abstract
  • Zhu, W; Ventevogel, MS; Knilans, KJ; Anderson, JE; Oldach, LM; McKinnon, KP; Hobbs, MM; Sempowski, GD; Duncan, JA. Neisseria gonorrhoeae suppresses dendritic cell-induced, antigen-dependent CD4 T cell proliferation. PLoS One. 2012;7:e41260.  Abstract
  • Billard, MJ; Gruver, AL; Sempowski, GD. Acute endotoxin-induced thymic atrophy is characterized by intrathymic inflammatory and wound healing responses. PLoS One. 2011;6:e17940.  Abstract
  • Cain, DW; Snowden, PB; Sempowski, GD; Kelsoe, G. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS One. 2011;6:e19957.  Abstract
  • Gordy, C; Pua, H; Sempowski, GD; He, YW. Regulation of steady-state neutrophil homeostasis by macrophages. Blood. 2011;117:618-629.  Abstract
  • Jin, C; Shelburne, CP; Li, G; Potts, EN; Riebe, KJ; Sempowski, GD; Foster, WM; Abraham, SN. Particulate allergens potentiate allergic asthma in mice through sustained IgE-mediated mast cell activation. Journal of Clinical Investigation. 2011;121:941-955.  Abstract
  • Pastva, AM; Mukherjee, S; Giamberardino, C; Hsia, B; Lo, B; Sempowski, GD; Wright, JR. Lung effector memory and activated CD4+ T cells display enhanced proliferation in surfactant protein A-deficient mice during allergen-mediated inflammation. Journal of Immunology. 2011;186:2842-2849.  Abstract
  • Shi, X; Zhang, P; Sempowski, GD; Shellito, JE. Thymopoietic and bone marrow response to murine Pneumocystis pneumonia. Infection and Immunity. 2011;79:2031-2042.  Abstract