Neural Stem Cell Institute, Rensselaer NY

Stem cell research and applications in the treatment of diseases like Retinitis Pigmentosis, Alzheimer's, Parkinson's, Spinal Cord Injury, Retinal Degeneration. Home of SallyTemple's lab.

 

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.

  1. Davis RJ, Alam NM, Zhao C, Müller C, Saini JS, Blenkinsop TA, Mazzoni F, Campbell M, Borden SM, Charniga CJ, Lederman PL, Aguilar V, Naimark M, Fiske M, Boles N, Temple S, Finnemann SC, Prusky GT, Stern JH. The Developmental Stage of Adult Human Stem Cell-Derived Retinal Pigment Epithelium Cells Influences Transplant Efficacy for Vision Rescue. Stem Cell Reports. 2017 Jul 11;9(1):42-49. PubMed PMID: 28625537; PubMed Central PMCID: PMC5511099.
  2. Davis RJ, Blenkinsop TA, Campbell M, Borden SM, Charniga CJ, Lederman PL, Frye AM, Aguilar V, Zhao C, Naimark M, Kiehl TR, Temple S, Stern JH. Human RPE Stem Cell-Derived RPE Preserves Photoreceptors in the Royal College of Surgeons Rat: Method for Quantifying the Area of Photoreceptor Sparing. J Ocul Pharmacol Ther. 2016 Jun;32(5):304-9. PubMed PMID: 27182605.
  3. Stanzel BV, Liu Z, Somboonthanakij S, Wongsawad W, Brinken R, Eter N, Corneo B, Holz FG, Temple S, Stern JH, Blenkinsop TA. Human RPE stem cells grown into polarized RPE monolayers on a polyester matrix are maintained after grafting into rabbit subretinal space. Stem Cell Reports. 2014 Jan 14;2(1):64-77. PubMed PMID: 24511471; PubMed Central PMCID: PMC3916756.
  4. Salero E, Blenkinsop TA, Corneo B, Harris A, Rabin D, Stern JH, Temple S. Adult human RPE can be activated into a multipotent stem cell that produces mesenchymal derivatives. Cell Stem Cell. 2012 Jan 6;10(1):88-95. PubMed PMID: 22226358.

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.

  1. Stern JH, Knutsson H, MacLeish PR. Divalent cations directly affect the conductance of excised patches of rod photoreceptor membrane. Science. 1987 Jun 26;236(4809):1674-8. PubMed PMID: 3037695.
  2. MacLeish PR, Stern JH. Direct effects of divalent cations and cyclic GMP on excised patches of rod outer segment membrane. Neurosci Res Suppl. 1987;6:S67-74. PubMed PMID: 2825087.
  3. Stern JH, Kaupp UB, MacLeish PR. Control of the light-regulated current in rod photoreceptors by cyclic GMP, calcium, and l-cis-diltiazem. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1163-7. PubMed PMID: 3006029; PubMed Central PMCID: PMC323032.
  4. Stern JH, Lisman JE. Internal dialysis of Limulus ventral photoreceptors. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7580-4. PubMed PMID: 6961434; PubMed Central PMCID: PMC347384.

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.

  1. Haller JA, Stalmans P, Benz MS, Gandorfer A, Pakola SJ, Girach A, Kampik A, Jaffe GJ, Toth CA. Efficacy of intravitreal ocriplasmin for treatment of vitreomacular adhesion: subgroup analyses from two randomized trials. Ophthalmology. 2015 Jan;122(1):117-22. PubMed PMID: 25240630.
  2. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012 Dec;119(12):2537-48. PubMed PMID: 23084240.
  3. Stern JH, Calvano C, Simon JW. Recurrent endogenous candidal endophthalmitis in a premature infant. J AAPOS. 2001 Feb;5(1):50-1. PubMed PMID: 11182674.
  4. Spray DC, Stern JH, Harris AL, Bennett MV. Gap junctional conductance: comparison of sensitivities to H and Ca ions. Proc Natl Acad Sci U S A. 1982 Jan;79(2):441-5. PubMed PMID: 6281771; PubMed Central PMCID: PMC345759.

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.

  1. Saini JS, Corneo B, Miller JD, Kiehl TR, Wang Q, Boles NC, Blenkinsop TA, Stern JH, Temple S. Nicotinamide Ameliorates Disease Phenotypes in a Human iPSC Model of Age-Related Macular Degeneration. Cell Stem Cell. 2017 May 4;20(5):635-647.e7. PubMed PMID: 28132833; PubMed Central PMCID: PMC5419856.
  2. Stern J, Eveleth D, Masula J, Temple S. Slow progression of exudative age related macular degeneration associated with hypertrophy of the retinal pigment epithelium. F1000Res. 2014;3:293. PubMed PMID: 25685325; PubMed Central PMCID: PMC4314661.
  3. Rabin DM, Rabin RL, Blenkinsop TA, Temple S, Stern JH. Chronic oxidative stress upregulates Drusen-related protein expression in adult human RPE stem cell-derived RPE cells: a novel culture model for dry AMD. Aging (Albany NY). 2013 Jan;5(1):51-66. PubMed PMID: 23257616; PubMed Central PMCID: PMC3616231.
  4. De S, Rabin DM, Salero E, Lederman PL, Temple S, Stern JH. Human retinal pigment epithelium cell changes and expression of alphaB-crystallin: a biomarker for retinal pigment epithelium cell change in age-related macular degeneration. Arch Ophthalmol. 2007 May;125(5):641-5. PubMed PMID: 17502503.

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.

  1. Lowry N, Goderie SK, Lederman P, Charniga C, Gooch MR, Gracey KD, Banerjee A, Punyani S, Silver J, Kane RS, Stern JH, Temple S. The effect of long-term release of Shh from implanted biodegradable microspheres on recovery from spinal cord injury in mice. Biomaterials. 2012 Apr;33(10):2892-901. PubMed PMID: 22243800.
  2. Lotz S, Goderie S, Tokas N, Hirsch SE, Ahmad F, Corneo B, Le S, Banerjee A, Kane RS, Stern JH, Temple S, Fasano CA. Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding. PLoS One. 2013;8(2):e56289. PubMed PMID: 23437109; PubMed Central PMCID: PMC3577833.
  3. Stern J, Temple Stern S. , inventors. Regenerative Research Foundation, assignee. METHODS FOR CULTURING UNDIFFERENTIATED CELLS USING SUSTAINED RELEASE COMPOSITIONS. US 20130337562.
  4. Stern J, Temple S. Retinal pigment epithelial cell proliferation. Exp Biol Med (Maywood). 2015 Aug;240(8):1079-86. PubMed PMID: 26041390; PubMed Central PMCID: PMC4935281.

A complete list of Dr. Stern’s published work can be found on the NCBI website.