Regina Clemens, M.D., Ph.D.

Assistant Professor
Pediatrics
Critical Care Medicine

Immunology Program
Molecular Cell Biology Program

  • clemensra@wustl.edu

  • The mechanisms regulating calcium-dependent neutrophil activation

Research Abstract:

Neutrophils are a critical component of the innate immune system. These cells lead host defense against
pathogens, but also inflict devastating tissue damage in inflammatory conditions. Understanding the signaling
pathways that regulate neutrophil activation can contribute to our understanding and identify therapeutic
targets for manipulation of inflammatory disease. Calcium is an evolutionarily conserved signaling molecule
that enters immune cells via a process termed store-operated calcium entry (SOCE). My current research
focuses on the calcium sensing STIM proteins and the ORAI calcium channels to determine the molecular
machinery required for SOCE in neutrophils, define the requirement for calcium signaling for key neutrophil
functions, and determine how disrupted calcium signaling impacts neutrophil-mediated tissue damage during
ALI in vivo. We have a unique repertoire of mice bearing neutrophil specific deletion in Stim1, Stim2, Orai1 and
Orai2 and developed an array of techniques for studying neutrophil activation and models of sepsis and acute
lung injury. Furthermore, we are interested in how calcium signaling is modulated during inflammation by a
multitude of factors including receptor levels, expression of STIM and ORAI store-operate calcium machinery
and alterations in cellular handling of other ions, which can have profound effects on the cell calcium response
due to changes in electrochemical gradient driving calcium entry. We anticipate that dynamic changes in
calcium responsiveness allow the host to regulate the immune response, however dysregulation of this
process may contribute to pathophysiology of infection and inflammation. Our lab has expertise in studying
calcium and other functional responses of human and mouse neutrophils by flow cytometry, a method that
allows single cell and population-based analysis of cellular responses in order to detect and analyze neutrophil
heterogeneity.

Selected Publications:

STIM1 and STIM2 cooperatively regulate mouse neutrophil store-operated calcium entry and cytokine production.
Clemens RA, Chong J, Grimes D, Hu Y, Lowell CA.
Blood. 2017; 130(13):1565-1577.

Store-operated calcium signaling in neutrophils.
Clemens RA, Lowell CA.
Journal of leukocyte biology. 2015; 98(4):497-502.

STIM1 calcium sensor is required for activation of the phagocyte oxidase during inflammation and host defense.
Zhang H, Clemens RA, Liu F, Hu Y, Baba Y, Theodore P, Kurosaki T, Lowell CA.
Blood. 2014; 123(14):2238-49.

Last Updated: 8/14/2019 2:01:19 PM

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