Novel therapeutics targeting ion channels

  • Screen small molecular inhibitors of the CRAC channel
  • Photo-inducible cell-ablation therapy
  • Use of iPS technology to study ion channelopathies 

Small molecule inhibitors of the SOC channel

        Drug candidates that specifically target the highly calcium-selective CRAC channels have the potential to suppress immune function selectively and may lack the toxicity of current immunosuppressive agents, such as cyclosporine A and FK506. In addition, abnormal SOCE is known to induce a higher rate of focal adhesion turnover and increased migration of metastatic cancer cells. This adverse effect can be effectively attenuated by knockdown of ORAI1/STIM1. Thus, we will examine the therapeutic values of specific small molecule inhibitors of the SOC channels in the treatment of autoimmune diseases and attenuation of tumor metastasis.

 

Use iPS cells technology to investigate ion channelopathies 

         The long-term goal in this endeavor is to create human models of cardiovascular and neurological channelopathies by generating iPS cell-derived cardiac or neuronal cells from fibroblasts from patients, to establish pharmacology profiles of known drugs used to treat each model, as well as to uncover drugs that may be of therapeutic value in treating these disorders. These cells also have the potential to be used in regenerative therapy, to restore function to damaged or failing organs without fear of autoimmune rejection. At the initial stage,  we will focus on patients with Brugada syndrome, a genetic disease that is characterized by abnormal electrocardiogram (ECG) recordings with typical ST segment elevation in the anterior precordial leads V1-V3 and an increased risk of sudden death due to ventricular fibrillation in heart.

 

 

ECG (leads V1-V3) in a normal person (A) and a patient with Brugada-syndrome (B) [adapted from http://en.wikipedia.org/wiki/Brugada_syndrome]