Criss Hartzell, PhD
Criss Hartzell’s laboratory is interested in many kinds of ion channels, though presently its main interest is devoted to channels that transport chloride ions. One reason for this is the belief that it is possible that more people have been killed by diseases that affect chloride channels than any other disease – for example, cholera, diarrheal diseases of infancy, and cystic fibrosis all involve chloride channel function. Prof. Hartzell and his colleagues are particularly interested in one family of ten genes called TMEM16 or ANO, because they are linked to a diverse spectrum of human diseases including at least two types of muscular dystrophy (LGMD2L and MMD3, ANO5), spinocerebellar ataxia (ANO10), dystonia and febrile seizures (ANO3), a bleeding disorder (Scott’s Syndrome, ANO6), and cancer (ANO1, ANO7, ANO9).
Although it was initially believed that all 10 ANO genes encoded chloride channels, Prof. Hartzell and other investigators were surprised to find that the family is functionally diverse. Although some ANOs are chloride channels, others are thought to be channels (“scramblases”) that transport lipids between the leaflets of the membrane bilayer. Prof. Hartzell and colleagues are interested in understanding how these proteins work on a molecular level: how are they activated and how they conduct their substrates (ions and/or lipids)? They are also interested in how mutations in these proteins produce human disease, particularly ANO5 muscular dystrophies. The team are using stem cells from ANO5 patients as well as genetically engineered muscle cell lines to investigate how ANO5 mutations affect muscle cell biology.