Prof. Armin Pause's lab focuses on:

• The molecular and cellular biology of the tumour suppressor folliculin (FLCN) and TFE3, its function and regulation in breast cancer progression.
• The mechanism of FLCN inhibition with respect to AMPK sensing activity as well as the effect of FLCN loss and AMPK activation in malignant cells.

Dr. Pause’s research interests focus on the molecular biology of energy-sensing pathways that are involved in the oncogenic transformation of normal cells. 
The Birt-Hogg-Dubé (BHD) syndrome is a hereditary human cancer syndrome that predisposes affected individuals to develop renal carcinoma of nearly all subtypes, as well as benign fibrofolliculomas, pulmonary, colon and renal cysts, caused by loss of-function mutations in the FLCN gene. FLCN was identified as an AMPK binding partner and his group has demonstrated that FLCN is an evolutionarily conserved negative regulator of AMPK. 
Loss of FLCN constitutively activates AMPK, resulting in PGC-1α-mediated mitochondrial biogenesis, increased ROS production, which induces HIF transcriptional activity and triggers Warburg metabolic reprogramming. This reprogramming stimulates cellular bioenergetics and conferres a HIF-dependent tumorigenic advantage in FLCN-negative cancer cells. 
Loss of FLCN results in constitutive AMPK-dependent induction of autophagy, inhibition of apoptosis, enhanced cellular bioenergetics, and resistance to energy-depleting stresses including oxidative stress, heat, anoxia, and serum deprivation. We further showed that AMPK activation conferred by FLCN loss is independent of the cellular energy state suggesting that FLCN controls the AMPK energy sensing ability. Together, our data suggest that FLCN is an evolutionarily conserved regulator of AMPK signaling that acts as a tumour suppressor by negatively regulating AMPK function. Their current work is now aimed at studying the mechanism of FLCN inhibition with respect to AMPK sensing activity as well as the effect of FLCN loss and AMPK activation in tumour progression in various human cancer.