Sign in to edit your profile (add interests, mentoring, photo, etc.)
    Last Name

    Claudio Punzo PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    AddressUniversity of Massachusetts Medical School
    368 Plantation Street, AS6-2041
    Worcester MA 01605-2324
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentGene Therapy Center

      InstitutionUMMS - School of Medicine

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentTranslational Science


        Lab web-page:


        Harvard Medical School, Boston, MA, USA
        Postdoctoral fellow, Laboratory of Dr. C.L. Cepko
        Biozentrum,University of Basel, Basel, Switzerland
        Doctor of Philosophy, Laboratory of Dr. W.J. Gehring
        University of Basel, Basel Switzerland
        Undergraduate studies, Mentored by Dr. W.J. Gehring

        Neuro-Degeneration in the Retina

        Dr. Claudio PunzoThe vertebrate retina has highly specialized sensory neurons, the photoreceptors (PR), which serve to initiate the process of vision. Cone PRs are responsible for vision during the brighter light intensities of the day and mediate color vision. Rod PRs are 1000x more sensitive to light, and initiate vision in dim light. The light captured by PRs is converted into an electrical signal that is passed on to bipolar cells and then to ganglion cells, the output neurons of the retina, that project to the brain.

        Blindness is the inevitable end stage of neuro-degeneration in the retina. The two cell types in the retina that are associated with loss of vision in humans are either the ganglion cells or the PRs. Loss of ganglion cells results in Glaucoma. Loss PRs is associated with a large number of retinal degeneration (RD) diseases. Since PRs account for ~75% of all cells in the retina loss of PRs results always in sever RD.

        The research focus in my lab is on RD diseases that affect photoreceptors. Retinitis Pigmentosa (RP) is a family of inherited RD that is untreatable and leads to blindness. The pathology is characterized by an initial loss of night vision due to the loss of rod PR, followed by a progressive loss of cone PRs. In many cases, the disease-causing allele is a gene exclusively expressed in rods; nonetheless, cones die too. There is no known form of RD in humans or mice where rods die, and cones survive. In contrast, mutations in cone-specific genes result only in cone death. Understanding this non-autonomous cone death is the key in designing therapeutic strategies. While the dependence of cones on rods plays an important role in RP it remains a fundamental question of retinal biology.

        Our recent studies on RP have led us to propose that cone death is preceded by metabolic changes in cone PRs and that, cones die due to nutrient deprivation. This hypothesis is based on changes seen in the Insulin/mTOR pathway and the role the individual members play in cones during degeneration (Fig. 1, 2). How could the observations of nutritionally deprived cones explain the dependence of cones on rods? PR outer segments (OS) interact with the Retinal-Pigmented Epithelium (RPE), which a single sheet of cells adjacent to the PR layer. The OS-RPE interactions are vital since the RPE provides nutrition and oxygen to PRs. Roughly 95% of all PRs in mouse and human are rods and approximately 20-30 OSs contact one RPE cell. Thus, only 1-2 of those RPE-OS contacts are via cones. During the collapse of the PR layer, the few remaining cone:RPE interactions are likely perturbed. If these interactions drop below a threshold required for the proper flow of nutrients, the loss of rods might result in a reduced flow of nutrients to cones. By cross-comparing 4 mouse models of RP we found in our studies that cone death starts always at the same density of leftover rods, meaning after 90% of rods have died. This cell density could represent the crucial threshold of remaining cells after which flow of nutrition is perturbed. This mechanism would also explain why the loss of cones does not lead to rod death. Since in humans and mouse, cones are less than 5% of all PRs, the critical threshold that perturbs OS-RPE interactions would not be reached.

        Areas of research interest in the laboratory include the role of molecular signaling pathways such as the Insulin/mTOR pathway in photoreceptor homeostasis and diseases. PRs are among the highest energy consuming cells in the human body. However, how PRs metabolize energy and how they respond to insults and stress is largely understudied. The knowledge gained on PR metabolism by studying diseases such as RP could help us in the future to treat more widespread diseases such as diabetic retinopathy or age-related macular degeneration. Another area of interest includes understanding the upstream and downstream signaling events of the apoptotic pathway that leads to cone cell death.

        Fig. 1. Insulin levels affect cone survival in the Retinitis Pigmentosa mutant PDE-b.

        Fig. 1. Insulin levels affect cone survival in the Retinitis Pigmentosa mutant PDE-b. (a-c) Retinal flat mounts of PDE-b mutants at postnatal week 7 stained for lacZ to detect surviving cones (blue color). (a) Example of untreated control. (b) Example of mouse injected with streptozotocin. Streptozotocin kills the b-cells in the pancreas thereby removes endogenous insulin. (c) Example of mouse injected daily with insulin to increase endogenous insulin.

        Fig. 2. Phosphorylation of mTOR (p*-mTOR) in wild type retinae.

        Fig. 2. (A) shows immunofluorescence on retinal flat mounts (photoreceptor side up) and (b, c) show retinal sections. Blue shows the nuclear DAPI stain. (a-c) p*-mTOR levels in wild type retinae. (a) Dorsal (up) enrichment of p*-mTOR. Higher magnification of dorsal and ventral region is shown to the right showing p*-mTOR in red and cone segments in green as detected by PNA. (b, c) Dorsal retinal sections stained for p*-mTOR (red signal) and PNA (b) (green signal) or a-b-galactosidase (c) (green signal). The b-galactosidase is under the control of the human red/green opsin promoter and is expressed in all cones.

        Rotation Projects


        The rotation projects outlined here can be integrated into a Ph.D. thesis if the candidate desires to continue with this line of research. In my lab we use molecular biology, genetics, histology, virology and surgical procedures on mice to conduct our research. You will be working in an environment that is focused on translational research and the goal of the lab is to move as quickly as possible from a basic science discovery to a therapeutic application. The basic science research the lab is conducting focuses around the role of metabolism and the Insulin/mTOR pathway.

        The following projects are available:

        1. Studying the role of the different Insulin/mTOR pathway member during degeneration.
        2. Study the loss of retinal specific proteins during degeneration.
        3. Generating mouse lines that allow cone cells to synthesize their own glucose.
        4. Studying the up- and downstream signaling of caspase mediated cell death in cones.

        selected publications
        List All   |   Timeline
        1. Zieger M, Punzo C. Improved cell metabolism prolongs photoreceptor survival upon retinal-pigmented epithelium loss in the sodium iodate induced model of geographic atrophy. Oncotarget. 2016 Mar 1; 7(9):9620-33.
          View in: PubMed
        2. Petit L, Punzo C. mTORC1 sustains vision in retinitis pigmentosa. Oncotarget. 2015 Jul 10; 6(19):16786-7.
          View in: PubMed
        3. Cepko C, Punzo C. Cell metabolism: Sugar for sight. Nature. 2015 Jun 25; 522(7557):428-9.
          View in: PubMed
        4. Ma S, Venkatesh A, Langellotto F, Le YZ, Hall MN, Rüegg MA, Punzo C. Loss of mTOR signaling affects cone function, cone structure and expression of cone specific proteins without affecting cone survival. Exp Eye Res. 2015 Jun; 135:1-13.
          View in: PubMed
        5. Venkatesh A, Ma S, Le YZ, Hall MN, Rüegg MA, Punzo C. Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice. J Clin Invest. 2015 Apr; 125(4):1446-58.
          View in: PubMed
        6. Banday AR, Baumgartner M, Al Seesi S, Karunakaran DK, Venkatesh A, Congdon S, Lemoine C, Kilcollins AM, Mandoiu I, Punzo C, Kanadia RN. Replication-dependent histone genes are actively transcribed in differentiating and aging retinal neurons. Cell Cycle. 2014; 13(16):2526-41.
          View in: PubMed
        7. Venkatesh A, Ma S, Langellotto F, Gao G, Punzo C. Retinal gene delivery by rAAV and DNA electroporation. Curr Protoc Microbiol. 2013; Chapter 14:Unit 14D.4.
          View in: PubMed
        8. Molnar T, Barabas P, Birnbaumer L, Punzo C, Kefalov V, Križaj D. Store-operated channels regulate intracellular calcium in mammalian rods. J Physiol. 2012 Aug 1; 590(Pt 15):3465-81.
          View in: PubMed
        9. Hafler BP, Surzenko N, Beier KT, Punzo C, Trimarchi JM, Kong JH, Cepko CL. Transcription factor Olig2 defines subpopulations of retinal progenitor cells biased toward specific cell fates. Proc Natl Acad Sci U S A. 2012 May 15; 109(20):7882-7.
          View in: PubMed
        10. Punzo C, Xiong W, Cepko CL. Loss of daylight vision in retinal degeneration: are oxidative stress and metabolic dysregulation to blame? J Biol Chem. 2012 Jan 13; 287(3):1642-8.
          View in: PubMed
        11. Huang W, Xing W, Ryskamp DA, Punzo C, Križaj D. Localization and phenotype-specific expression of ryanodine calcium release channels in C57BL6 and DBA/2J mouse strains. Exp Eye Res. 2011 Nov; 93(5):700-9.
          View in: PubMed
        12. Križaj D, Huang W, Furukawa T, Punzo C, Xing W. Plasticity of TRPM1 expression and localization in the wild type and degenerating mouse retina. Vision Res. 2010 Nov 23; 50(23):2460-5.
          View in: PubMed
        13. Punzo C, Kornacker K, Cepko CL. Stimulation of the insulin/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa. Nat Neurosci. 2009 Jan; 12(1):44-52.
          View in: PubMed
        14. Kanadia RN, Clark VE, Punzo C, Trimarchi JM, Cepko CL. Temporal requirement of the alternative-splicing factor Sfrs1 for the survival of retinal neurons. Development. 2008 Dec; 135(23):3923-33.
          View in: PubMed
        15. Plaza S, Prince F, Adachi Y, Punzo C, Cribbs DL, Gehring WJ. Cross-regulatory protein-protein interactions between Hox and Pax transcription factors. Proc Natl Acad Sci U S A. 2008 Sep 9; 105(36):13439-44.
          View in: PubMed
        16. Punzo C, Cepko CL. Ultrasound-guided in utero injections allow studies of the development and function of the eye. Dev Dyn. 2008 Apr; 237(4):1034-42.
          View in: PubMed
        17. Liu F, Jenssen TK, Trimarchi J, Punzo C, Cepko CL, Ohno-Machado L, Hovig E, Kuo WP. Comparison of hybridization-based and sequencing-based gene expression technologies on biological replicates. BMC Genomics. 2007; 8:153.
          View in: PubMed
        18. Punzo C, Cepko C. Cellular responses to photoreceptor death in the rd1 mouse model of retinal degeneration. Invest Ophthalmol Vis Sci. 2007 Feb; 48(2):849-57.
          View in: PubMed
        19. Kuo WP, Liu F, Trimarchi J, Punzo C, Lombardi M, Sarang J, Whipple ME, Maysuria M, Serikawa K, Lee SY, McCrann D, Kang J, Shearstone JR, Burke J, Park DJ, Wang X, Rector TL, Ricciardi-Castagnoli P, Perrin S, Choi S, Bumgarner R, Kim JH, Short GF, Freeman MW, Seed B, Jensen R, Church GM, Hovig E, Cepko CL, Park P, Ohno-Machado L, Jenssen TK. A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies. Nat Biotechnol. 2006 Jul; 24(7):832-40.
          View in: PubMed
        20. Punzo C, Plaza S, Seimiya M, Schnupf P, Kurata S, Jaeger J, Gehring WJ. Functional divergence between eyeless and twin of eyeless in Drosophila melanogaster. Development. 2004 Aug; 131(16):3943-53.
          View in: PubMed
        21. Punzo C, Seimiya M, Flister S, Gehring WJ, Plaza S. Differential interactions of eyeless and twin of eyeless with the sine oculis enhancer. Development. 2002 Feb; 129(3):625-34.
          View in: PubMed
        For assistance with using Profiles, please refer to the online tutorials or contact UMMS Help Desk or call 508-856-8643.
        Claudio's Networks
        Click the "See All" links for more information and interactive visualizations!
        Similar People
        Same Department
        Physical Neighbors

        This is an official Page/Publication of the University of Massachusetts Worcester Campus
        Office of the Vice Provost for Research, 55 Lake Ave North, Worcester, Massachusetts 01655
        Questions or Comments? Email: Phone: 508-856-1572