Professor, Departments of Medical Genetics and Surgery; Roy and Joan Allen Professor in Sight Research
3330 Hospital Drive NW
Calgary, Alberta, T2N 4N1
Genetics of human eye diseases
Other Area(s) of Research:
Genetics of depression and learning / memory
Genetics of neurotransmission and synaptogenesis
My research focuses on the molecular genetics of retinal neurotransmission. As a geneticist, I got into this area of neurobiology by investigating the genetic causes of a group of patients with impaired night blindness, who have abnormal retinal neurotransmission. Our gene mapping studies lead to the discovery that mutations in the CACNA1F gene, which encodes Cav1.4, and NYK, which encodes the novel protein nyctalopin, causes different forms of congenital stationary night blindness (CSNB). Our findings have thus provided definitive DNA diagnosis for two forms of CSNB. Further studies found that mutations in the GRM6 gene, which codes for the glutamate receptor, mGLUR6, also causes CSNB. these genetic studies were thus able to dissect out critical functions in retinal synapse function and structure. We continue to extend the indentification of the genetic causes of CSNB in patients in whom the gene is still unknown.
Subsequently, we knocked out the Cacna1f gene in the mouse; studies of these mutant mice, which lack the Cav1.4 channel, found that photoreceptor sysnapses were not forming. This provides an explanation for the failure in retinal neurotransmission seen in CSNB patients with mutations in this gene. With the Cacna1f-KO mouse we are now in a position to investigate whether gene therapy can re-establish photoreceptor sysnapses and provide recovery of sight in Cacna1f knockout mice (collaboration with Dr. W. Stell). Such studies are of fundamental interest in context of learning about the plasticity of the photoreceptor synapses and may have potential benefit for patients with CSNB.
We are also studying the variability in clinical features in genetically characterized CSNB patients and how this may be influenced by different gene mutations. Such information will be of help to the retinal specialists who see these patients.
Our interest in the genetics of synpatogenesis have provided a springboard for collaborative studies on genetic risk factors for depression (studies with Dr. R. Ramasubbu) and for SIDS (studies with Dr. R. Wilson), and the genetics of learning and memory in mice (studies with Dr. F. Biddle). Each of these studies is ongoing.