Jeffrey Stern, M.D., Ph.D.
Dr. Stern’s retina career began with studying early steps in vision, photoreceptor cell excitation, and gap junctional conductance between photoreceptor cells. After this, he pursued clinical retina practice which provided additional valuable research direction. In 2007, Drs. Stern and Sally Temple co-founded the Neural Stem Cell Institute where they discovered the sub-population of stem cells in the human retinal pigment epithelial (RPESC). In 2010 they organized the Retinal Stem Cell Consortium for preclinical IND-enabling work on RPESC transplantation as therapy for dry Age-related Macular Degeneration (AMD). They discovered that less differentiated RPE progenitor cells were more reparative than highly differentiated ones. His current research focus is to compare younger progenitor cells with mature fully differentiated RPE cells to identify the pathways underlying improved vision rescue. In 2013, Dr. Stern received the Audacious Goals Prize from the National Eye Institute, and in 2015 he was named the Professional of the Year by the Northeast Association for the Blind.
Dr. Stern’s Contributions to Science
As a PhD student, Dr. Stern’s research focused on understanding the cytoplasmic signals that mediate signal transduction during photoreceptor cell excitation and adaptation, which has broad significance. During his graduate studies in Dr. John Lisman’s lab, Dr. Stern modified Kostyuk’s internal perfusion technique to control the cytoplasmic composition of living photoreceptor cells. The internal perfusion technique is the predecessor of whole cell patch clamp. His work provided the first such recordings from neurons and described roles for calcium, nucleotides and an un-identified quaternary amine as second messengers in the phototransduction cascade. Subsequently, with Peter MacLeish in Torsten Wiesel’s laboratory, he applied the patch clamp technique to describe the first blocker of photoreceptor cell cGMP-activated channels.
During his postdoctoral research in the Laboratory of Neurobiology at Rockefeller University with Drs. Torsten Wiesel and Peter MacLeish, Dr. Stern focused on early visual signal processing by gap junctions. He developed a dual ‘whole cell patch clamp’ technique to study the electrical synapse between photoreceptor cells. The voltage-sensitivity of rod-rod synapses that they found was not published due to his transition to clinical training. Concurrent research with Drs. Michael Bennett and David Spray applied the dual patch clamp technique to pairs of blastocyst cells was published to settle a major question of the time by finding much greater sensitivity of gap junctional conductance to hydrogen than calcium ion. In his clinical work, he served as site PI for a variety of clinical studies.
Dr. Stern’s research also involves the retinal pigment epithelium. Although retinal pigment epithelial (RPE) cell proliferation and wound repair can be robust in animal models and in vitro, limited regeneration occurs in the human RPE layer. Drs. Stern, Soma De, and Sally Temple found that RPE cells remodel in AMD to change phenotype and express drusen proteins. After this, together with Drs. Enrique Salero, Sally Temple, and others, they found a subpopulation of human RPE stem cells (RPESC) that self-renew and produce a variety of progeny types. Dr. Stern and colleagues- Drs. Janmeet Saini, Tim Blenkinsop, and Sally Temple discovered that stress conditions cause RPESC to produce progeny that over-express drusen protein. These ‘pathologic RPE progeny’ are used as a ‘disease in a dish’ model to study drusen formation. In related work, they described AMD patients with RPE hypertrophy that was associated with slowed disease progression, suggesting that RPE proliferation contributes to RPE layer wound repair in the AMD patient.
Stem cell technology depends on the discovery of growth factors to maintain proliferative stem cell cultures. These growth factors, however, are labile and degrade rapidly in culture media or tissue. Together with Dr. Sally Temple, he developed controlled-release growth factor microbeads that maintain stable growth factor levels in culture media. The StemBeads® are now used to improve cultures in hundreds of stem cell laboratories around the world. They are also developing therapeutic applications using Sonic Hedgehog beads to activate endogenous neural stem cells to promote self-repair after spinal cord injury and StemBeadsFGF2 to stimulate RPESC proliferation to counteract RPE cell loss for relevant degenerative retinal diseases such as AMD.