Biosketch

Thomas Weichhart is Associate Professor in Immunometabolism working at the Medical University of Vienna. He studied Biology & Genetics at the University of Vienna and was awarded a bachelor’s degree in 2000. In 2005, he completed his PhD at the University of Vienna. After postdoctoral training at the Medical University of Vienna, he become group leader in 2012 at the Medical University of Vienna. With his team, he tries to understand how macrophages influence metabolism to contribute to homeostasis and disease. He is coordinator of a special research program in Austria focused on Immunometabolism (www.immunometabolism.at)

Research profile

mTOR inhibitors have been used as immunosuppressive agents since 1999 in clinical medicine to prevent rejection after organ transplantation. A lot of work has focused on the role mTOR in T and B lymphocytes. However, the role of mTOR in the innate immune system that is monocytes, macrophages and dendritic cells has not been thoroughly addressed. We could show that inhibition of mTOR has surprising immunostimulatory effects on monocytes and dendritic cells and therefore, influences the outcome of bacterial infections. In such a way, inhibition of mTOR in these cells is even able to enhance adaptive T-cell responses and could be used to enhance vaccination efficiencies in certain population groups. On the one hand, these results paved to way to explain certain proinflammatory side effects of these inhibitors that have been observed in patients but were never understood. Moreover, our results laid the basis for including mTOR inhibitors as vaccination agents for immunotherapy in cancer.

Main research questions:

  • Role of mTOR signaling in innate immune cells
  • How do macrophages promote granulomatous disease with a special focus on sarcoidosis
  • What metabolites do macrophages secrete that influence tissue homeostasis and disease?

We could recently show that chronic activation of the metabolic checkpoint kinase mTORC1 in macrophages is sufficient to induce spontaneous granuloma formation in mice. This represents the first signaling pathway described in macrophages that is needed and sufficient to form epithelioid granulomas. Moreover, we found that in the granulomatous disease sarcoidosis, mTOR activation is associated with a progressive form of disease. These results suggested mTOR inhibitors as novel therapeutic agents against sarcoidosis. This has been recently validated in a clinical trial. The group is further exploring metabolic pathway that contribute to granuloma formation.

Positions and training

2014 – Tenured Faculty Member, Associate Professor, Medical University of Vienna, Austria

2012 – Group leader, Institute of Medical Genetics, Medical University of Vienna

2010 – 2012 Junior group leader, Department of Internal Medicine III, Medical University of Vienna

Contributions

Coordinator of the FWF-funded special research program SFB Immunometabolism

Member of the European network for Immunometabolism (EFIS study group).



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