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Molecular Cardiology Research Institute
Retina Research Lab

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Retina Research Laboratory

Dr. Janis Lem's Retina Research Lab focuses on two major areas of study: The lab investigates the molecular mechanisms by which genetic mutations cause blinding retinal degenerations.  In addition, transgenic models are used to investigate G-protein coupled receptor signaling in the visual system.


Research Focus and Highlights
Retinitis pigmentosa (RP) is a retinal degenerative disease that affects approximately 1.5 million people worldwide. Currently, there is no effective cure for the disease. A major goal of our research is to elucidate the molecular mechanisms that trigger photoreceptor cell death. Mutations in several genes encoding proteins of the phototransduction cascade are associated with RP. This suggested that aberrant photosignaling might contribute to degeneration. To test this possibility, we used transgenic mice defective for rod transducin signaling. Our studies identified transducin-dependent and transducin-independent classes of retinal degenerations.


The transducin-dependent mutant degenerations are defective for terminating rhodopsin signaling. Blocking transducin signaling in these mutants prevents retinal degeneration. Thus persistent activation of phototransduction signaling causes degeneration, pointing to an activation event downstream of transducin that causes degeneration. Studies in the lab seek to identify this downstream event and its mechanism.


The transducin-independent degenerations are not protected when transducin signaling is blocked. Unexpectedly, blocking transducin signaling accelerated degeneration for some of these mutations. This suggested that the trigger for degeneration lies upstream of transducin. This led us to hypothesize that transducin, in addition to its canonical regulation of rhodopsin signaling, might also regulate non-canonical rhodopsin signaling. We have identified a transducin-independent rhodopsin signaling pathway that causes light-dependent protein kinase D activation and appears to regulate retina cell adhesion. Studies in the lab seek to elucidate the physiological function of this alternate signaling pathway and examine its role in retinal degeneration.


Research Administrator: Dionne Bradford

Lab Director

Janis Lem, Ph.D.

Tufts Medical Center

800 Washington Street, Box 5045

Boston, MA 02111

Janis Lem



Recent Publications


1. Palmitoylation stabilizes unliganded rod opsin. Proc. Natl. Acad. Sci. 2010 May.


2. Rhodopsin-mediated retinitis pigmentosa. Progress in Molecular Biology and Translational Science. 2009 Oct.  


3. Transgenic strategies for the analysis of photoreceptor function. In: Signal Transduction in the Retina.  S. Fliesler and O. Kisselev,CRC Press-Taylor and Francis Group, LLC, Boca Raton, FL.  2008 Jan. 


4.  A novel form of transducin-dependent retinal degeneration: Accelerated retinal degeneration in the absence of rod transducin.  Investigative Ophthalmology & Visual Science.  2007 Dec.


5. Enhanced shutoff of phototransduction in transgenic mice expressing palmitoylation-deficient rhodopsin. J Biol Chem. 2005 Jul.


6. Constitutive Opsin Signaling:  Night Blindness or Retinal Degeneration? Trends Mol Med.  2004 Apr.


7. Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis. Nat. Genet. 2003 Oct.


See All MCRI Publications