Research interest is a combination of monocarboxylate transporters; CD147; retinal pigmment epithelium; retinal metabolism; glycolysis, and JAM-C
The focus of my laboratory has been to study the expression, regulation and functional role of monocarboxylate transporters (MCTs) in maintaining metabolic homeostasis in the retina and normal vision. The Retina, like other neural tissue, has a high energy demand and is dependent on a continuous supply of oxygen and metabolic substrates from the blood to maintain visual activity. The primary energy substrate of the retina is glucose which is transported from the choroids blood supply to the outer retina by the retinal pigment epithelium (RPE). The majority of the glucose transported into the outer-retina is metabolized through anaerobic glycolysis in Müller glial cells thus producing large quantities of lactate which is utilized by photoreceptor cells to fuel oxidative phosphorylation and the excess lactate is transported out of the retina by the RPE.
We have taken an integrative approach in which we have combined genetic, biochemical, and imaging analysis to study the underlying molecular mechanisms. We characterized the expression of MCTs in the RPE and retina and identified a new member of this transporter family, MCT3. We showed that MCT3 is preferentially expressed in the basolateral membrane of the RPE and like MCT1 and MCT4; it requires association with an accessory protein, CD147 for efficient processing and trafficking to the plasma membrane. IN CD147 null mouse, which has impaired visual function; we found that there is a loss of MCT expression in the retina and the RPE suggesting that lactate homeostasis critical for visual function. Recently we generated a MCT3 null mouse and showed that there is a reduction in the amplitude of the rod photoreceptor a-wave and the rod and cone photoreceptor b-waves. The CD147 and the MCT3 null mice provide excellent model systems for studying how alterations in expression or distribution of these proteins could contribute to retinal disease.
Ongoing Projects in my lab include:
- Characterizing mechanisms regulating tissue specific trafficking of heteromeric transporter proteins in different epithelia.
- Identifying adaptor proteins that regulate trafficking of CD147 and MCT3 to the basolateral membrane and determine tissue specific and development patterns of expression.
- Characterizing the role of MCT12 in maintaining lens homeostasis and determine how mutations SLC16A12, an orphan member of the monocarboxylate acid transporter family cause age related and juvenile cataracts.
- Mechanism regulating age and disease related expressions of SLC16A8 in the retinal pigment epithelium.
- Investigate the dual role of tissue factor in the RPE: protecting the RPE against oxidative stress and enhancing the formation of epiretinal membranes after retinal detachment.
