Gregory Sempowski, PhD
Associate Professor
sempo001@mc.duke.edu

The Laboratory of T-Cell Biology and Immune Reconstitution is led by Gregory D. Sempowski, PhD and is located in the Global Health Research Building.  The lab includes Melissa Ventevogel, MS, Amanda Gruver, Kristina Riebe, Jeffrey Hale, MS, Heather Lynch, PhD, and Shelley Stewart (shared with Alam Lab).  The Sempowski lab has an independent research program studying immunoscenescence associated with aging, works collaboratively with Drs. Tom Kepler (Biostatistics) and S. Munir Alam (DHVI) modeling immunity for biodefense, and is home to two DHVI Shared Resource Facilities.   

Primarily, the Sempowski lab is focused on developing strategies to enhance T cell reconstitution in order to offset thymic immune depletion due to immunodeficiency associated with ageing, stress, or illness (Ventevogel, Riebe and Gruver).  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. 

 

The Sempowski lab works in close collaboration with the Alam lab (Lynch, Riebe and Stewart) to provide experimental immunology studies to a multi-institutional computational modeling effort called “Multiscale Systems Immunology for Adjuvant Development” directed by Duke’s Dr. Tom Kepler.  The team has investigated the correlation of the measurable antibody response to recombinant anthrax protective antigen (rPA) to in situ changes in germinal center B cell development and how these are affected by the use of alum as an adjuvant.  The rPA/adjuvant prime/boost study was designed with two main purposes in mind: first, to provide a systematic assay to determine the efficacy of adjuvanted vaccines against B. anthracis protective antigen; and second, to provide quantitative information on the kinetics of the primary humoral response to protective antigen to be used in subsequent computational models.

 

Lastly, the Sempowski laboratory contains a service component (J. Hale, Riebe).  This consists of the Immune Reconstitution & Biomarker Analysis Facility, and the Live Animal Imaging Facility.  The IR & Biomarker Facility provides access to specialized instrumentation for Real-Time qPCR and Luminex-based multiplex assays, and runs molecular assays to monitor thymic output in moue, human and non-human primate samples.  This facility is keeper of the patented Mouse TREC Assay (Sempowski, Haynes, Liao), which is performed regularly for investigators from all over the world.  This assay has proven invaluable for monitoring thymopoiesis in mice.  The Live Animal Imaging Facility is housed in an ABSL-3 animal suite in the GHRB.  The Facility has a state-of-the-art Xenogen Spectrum in vivo imaging system capable of noninvasive quantitative 3D molecular imaging of anesthetized mice, rats, rabbits and guinea pigs.  The instrument can quantify bioluminescence and fluorescence (490-850nm).  Ongoing research applications include: poxvirus gene expression, replication, and vaccine development (Pickup), Viral vector-based vaccine delivery and efficacy (Ramsburg), and in vivo tracking of novel vaccine components with fluorescent tags (Sempowski).