Ph.D., University of Illinois, Urbana-Champaign
Increased intracellular calcium via calcium channels triggers a variety of physiological events. Compared to high voltage-activated Ca2+ channel, the functions of the low voltage-activated or T-type Ca2+ channels are not completed understood. Three T-channel subunits have been identified: CaV3.1, CaV3.2 and CaV3.3, only CaV3.2 has been linked to human diseases. It has been demonstrated that mutations and polymorphisms in the human CaV3.2 gene are associated with childhood absence epilepsies, idiopathic generalized epilepsies and autism spectrum disorders. In addition, CaV3.2-null mice display abnormal coronary artery, reduced peripheral pain and fail to develop pathological cardiac hypertrophy.
The long term research goal of my laboratory is to understand the regulation, function and the downstream signaling pathways of CaV3.2 T-channels.To achieve this goal, several tasks are being actively pursued. (1) Investigate how CaV3.2 is regulated during pressure overload-induced pathological cardiac hypertrophy. We want to know what are the signals lead to upregulation of CaV3.2 in adult heart. (2) Study the interaction between CaV3.2 and calcineurin and the downstream signaling pathways activated by CaV3.2 T-currents using biochemical and phosphoproteomic approaches. (3) Delineate the underlying mechanism leads to the lack of acid-induced chronic muscle pain and abnormal tracheal malformation in CaV3.2-/- mice.
在正常的情形下，T-通道只表現在胚胎幼體時期，成體心室中並無T-通道。然而當心臟肥大及梗塞時，心肌細胞卻重新表現T-通道。目前我們已知Cav3.2 T-通道對病理性心臟肥大的發生是必要的。我們正在研究心臟肥大時，Cav3.2 是如何受調控的及鈣離子經由T-通道進入細胞後，引發何種訊息傳遞反應。