Research Focus

Cellular signaling events as they relate to health and disease are the central theme of my research. Over the past three decades I have been using biophysical and pharmacological approaches elucidating ion channel function and its relationship to cell signaling. Mediated by very fruitful national and international collaborations, I was able to incorporate molecular aspects to this work, which has led to the original identification and biophysical as well as functional characterization of several novel ion channels, including the channel-kinase TRPM7.

Our work identified TRPM7 as a central mechanism for magnesium homeostasis, and possibly trace metal regulation, in mammals. TRPM7, it turns out, is also centrally involved in mammalian embryonic development, and aggravation of outcome measures in ischemic stroke. Recent developments have placed TRPM7 at the center cell proliferation and cell cycle progression, prompting my research interests to move into tumor biology. In addition to elucidating the mechanisms involved in magnesium-dependent control of cell proliferation, we have screened natural product libraries for pharmacological activity on this target and identified Waixenicin A, a molecular produced by a Hawaiian soft coral, as a potent an highly specific inhibitor of TRPM7 and proliferative activity of tumor cells. The TRPM7 gene, its function and its pharmacological modulation by this compound have resulted in three patent application and numerous publications in the journals of Cell, Science and Nature.