Hermann Gram, PhD
Autoimmunity, Transplantation and Inflammation
Cytokines are critical signaling molecules in the perpetuation of inflammatory and autoimmune diseases. IL-1β is one of the most powerful cytokines in inflammatory diseases: it has a role not only in “classical” inflammatory conditions, but more recently its role in low-grade inflammatory conditions like type II diabetes, atherosclerosis, and vascular remodelling has been recognized. Antibodies that neutralize cytokines are powerful pharmacological tools to alleviate disease, and antibodies to IL-1β in particular have demonstrated activity in a large number of experimental inflammatory conditions in animals and a wide variety of human diseases. Antibodies targeting cellular components of the immune system such as T cells, NK cells, or B cells have demonstrated clinical efficacy in a number of autoimmune diseases. However, the precise mechanisms by which these antibodies act remain ill-defined in many instances. Cellular assays, mechanistic animal studies, and translational research on human tissue samples are suitable to shed light on the therapeutic mode of action of these antibodies.
Thus, the main research activities in the lab comprise:
- Understanding the role of human B cells and its regulation in autoimmunity
- Identification of the intracellular signaling components in monocyte/macrophages that regulate polarization and response to cytokines
Chakraborty A, Tannenbaum S, Rordorf C, Lowe P, Floch D, Gram H, Roy S.
Pharmacokinetic and pharmacodynamic properties of canakinumab, a human anti-interleukin-1β monoclonal antibody.
Clinical Pharmacokinetics. 2012;51(6):e1–e18
Clausen F, Hånell A, Israelsson C, Hedin J, Ebendal T, Mir A, Gram H, Marklund N.
Neutralization of interleukin-1β reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice.
The European Journal of Neuroscience. 2011;34(1):110–23.
Koziczak-Holbro M, Littlewood-Evans A, Pöllinger B, Kovarik J, Dawson J, Zenke G, Burkhart C, Müller M, Gram H.
The critical role of kinase activity of interleukin-1 receptor-associated kinase 4 in animal models of joint inflammation.
Arthritis and Rheumatism. 2009;60(6):1661–71.
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