Prof Shin-Ichi Ohnuma


Personal Profile

Name: Shin-Ichi Ohnuma Email:
Title: Prof Tel: 44 20 7608 4062
Department: Inst Ophthalmology - Ocular Biology Fax:
Position: Professor Address: Institute of Ophthalmology, UCL, 11-43 Bath Street, London, EC1V 9EL
Research Domain: Basic Life Sciences, Neuroscience, Personalised Medicine Web Page: Personal Web Page


Research Description

Embryonic retina is formed through a combination of multiple developmental processes including neural induction, eye field specification, eye cup formation, cell fate determination, lamination, and differentiation. Our aim is to understand the detailed molecular mechanism of whole retinogenesis. In particular, our main focus of research is on the mechanism of co-ordination of cell cycle regulation with developmental processes. Although the cell cycle needs to be co-ordinated with many aspects of developmental processes, and the defects of the co-ordination are the causes of many human diseases - such as cancer and some retinal disorders - little is known about the mechanism. To determine the mechanism, we use the amphibian retina as a model system. This system is ideal for detailed and fast functional analysis of retinogenesis. Through a combination of in vivo and in vitro approaches, our group is actively searching novel genes

Prof. Ohnuma aims to understand molecular mechanisms underlying human diseases through combination of in animal models, cell biology, and bio-informatics. He has been studying various human diseases from cancer to eye diseases. In particular, he is interested in age-related diseases including AMD, RP, glaucoma, and various cancers. Also, he is interested in construction of functional eye using retinal stem cells both in vivo and in vitro. Through these study, he aims to develop novel diagnosis and treatments of human diseases.

Research Activities

Retinal development, genetics, Xenopus

Education Description

Prof. Ohnuma is Director of PhD programme of the Sensory System, Technology, and Therapies (SenSyt). Also, he works for the Biology of Vision MSc and Cancer MSc.

UCL Collaborators

External Collaborators



    • Dellett M, Sasai N, Nishide K, Becker S, Papadaki V, Limb GA, Moore AT, Kondo T, Ohnuma S (2015). Genetic background and light-dependent progression of photoreceptor cell degeneration in Prominin-1 knockout mice.. Invest Ophthalmol Vis Sci, 56(1), 164 - 176. doi:10.1167/iovs.14-15479


    • Gichuhi S, Ohnuma S, Sagoo MS, Burton MJ (2014). Pathophysiology of ocular surface squamous neoplasia.. Exp Eye Res, 129, 172 - 182. doi:10.1016/j.exer.2014.10.015
    • Tsuchiya Y, Pham U, Hu W, Ohnuma S, Gout I (2014). Changes in acetyl CoA levels during the early embryonic development of Xenopus laevis.. PLoS One, 9(5), e97693 - . doi:10.1371/journal.pone.0097693


    • Hu W, Haamedi N, Lee J, Kinoshita T, Ohnuma S (2013). The structure and development of Xenopus laevis cornea.. Exp Eye Res, 116, 109 - 128. doi:10.1016/j.exer.2013.07.021
    • Wang F, Hu W, Xian J, Ohnuma S, Brenton JD (2013). The Xenopus Tgfbi is required for embryogenesis through regulation of canonical Wnt signalling.. Dev Biol, 379(1), 16 - 27. doi:10.1016/j.ydbio.2012.11.010


    • Takawa M, Cho HS, Hayami S, Toyokawa G, Kogure M, Yamane Y, Iwai Y, Maejima K, Ueda K, Masuda A, Dohmae N, Field HI, Tsunoda T, Kobayashi T, Akasu T, Sugiyama M, Ohnuma S, Atomi Y, Ponder BA, Nakamura Y, Hamamoto R (2012). Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression. Cancer Research, 72(13), 3217 - 3227. doi:10.1158/0008-5472.CAN-11-3701
    • Cho HS, Shimazu T, Toyokawa G, Daigo Y, Maehara Y, Hayami S, Ito A, Masuda K, Ikawa N, Field HI, Tsuchiya E, Ohnuma S, Ponder BA, Yoshida M, Nakamura Y, Hamamoto R (2012). Enhanced HSP70 lysine methylation promotes proliferation of cancer cells through activation of Aurora kinase B. Nature Communications, 3, 1072 - .
    • Dellett M, Hu W, Papadaki V, Ohnuma S (2012). Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.. Dev Growth Differ, 54(3), 327 - 340. doi:10.1111/j.1440-169X.2012.01339.x


    • Ohta K, Ito A, Kuriyama S, Lupo G, Kosaka M, Ohnuma S, Nakagawa S, Tanaka H (2011). Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4. P NATL ACAD SCI USA, 108(36), 14962 - 14967. doi:10.1073/pnas.1100513108


    • Bilitou A, Ohnuma S (2010). The role of cell cycle in retinal development: cyclin-dependent kinase inhibitors co-ordinate cell-cycle inhibition, cell-fate determination and differentiation in the developing retina.. Dev Dyn, 239(3), 727 - 736. doi:10.1002/dvdy.22223


    • Ohta K, Ito A, Kuriyama S, Lupo G, Nakayama R, Ohshima N, Kosaka M, Ohnuma S, Nakagawa S, Tanaka H (2009). Tsukushi is a Frizzled ligand that, in competition with Wnt2b, regulates the proliferation of retinal stem/progenitor cells. doi:10.1016/j.mod.2009.06.730
    • Mochizuki T, Bilitou A, Waters CT, Hussain K, Zollo M, Ohnuma S (2009). Xenopus NM23-X4 regulates retinal gliogenesis through interaction with p27Xic1.. Neural Dev, 4, 1 - . doi:10.1186/1749-8104-4-1
    • Bilitou A, Mochizuki T, Ohnuma SI (2009). Co-ordination of cell-cycle and cell fate determination in the Xenopus retina: An interplay of p27Xic1, Cyclin/cdks and NM23 proteins. doi:10.1016/j.mod.2009.06.564
    • Mochizuki T, Bilitou A, Waters CT, Hussain K, Zollo M, Ohnuma S (2009). Xenopus NM23-X4 regulates retinal gliogenesis through interaction with p27Xic1. Neural Dev., 4, 1 - .
    • Bilitou A, Watson J, Gartner A, Ohnuma SI (2009). The NM23 family in development. Mol.Cell Biochem., , - .
    • Bilitou A, Watson J, Gartner A, Ohnuma S (2009). The NM23 family in development.. Mol Cell Biochem, 329(1-2), 17 - 33. doi:10.1007/s11010-009-0121-6
    • Ohta K, Ito A, Kuriyama S, Lupo G, Nakayama R, Ohshima N, Kosaka M, Ohnuma S-I, Nakagawa S, Tanaka H (2009). Molecular function of Tsukushi on neuronal stem cells. NEUROSCIENCE RESEARCH, 65, S91 - S91. doi:10.1016/j.neures.2009.09.374


    • Ohta K, Ito A, Kuriyama S, Nakayama R, Oshima N, Kosaka M, Ohnuma S, Nakagawa S, Tanaka H (2008). Tsukushi is a Frizzled4 ligand that regulates the proliferation of retinal stem cells in competition with Wnt2b. NEUROSCIENCE RESEARCH, 61, S42 - S42.


    • Bilitou A, Ohnuma S (2007). Visualising the dynamics of retinogenesis in a live vertebrate embryo. doi:10.1016/j.ydbio.2007.03.454
    • Morris SA, Almeida AD, Ohta K, Ohnuma S-I (2007). Tsukushi refines germ layer formation through coordination of Nodal, FGF and BMP signalling. doi:10.1016/j.ydbio.2007.03.614
    • Morris SA, Almeida AD, Tanaka H, Ohta K, Ohnuma S (2007). Tukushi modulates Xnr2, FGF, and and BMP signalling: Regulation of Xenopus Germ Layer Formation. PLoS ONE, 2(10), e1004 - .
    • Ohta K, Ito A, Kuriyama S, Ohnuma S-I, Kosaka M, Nakagawa S-I, Tanaka H (2007). Tsukushi inhibits proliferation of retinal stem cells by Wnt signalling inhibition. NEUROSCIENCE RESEARCH, 58, S56 - S56. doi:10.1016/j.neures.2007.06.328
    • Morris SA, Almeida AD, Tanaka H, Ohta K, Ohnuma S (2007). Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ layer formation.. PLoS One, 2(10), e1004 - . doi:10.1371/journal.pone.0001004
    • Ohta K, Ito A, Kuriyama S, Ohnuma S, Kosaka M, Nakagawa S, Tanaka H (2007). Tsukushi inhibits the proliferation of retinal stem/progenitor cells. doi:10.1016/j.ydbio.2007.03.574


    • Harrington AE, Morris-Triggs SA, Ruotolo BT, Robinson CV, Ohnuma S, Hyvonen M (2006). Structural basis for the inhibition of activin signalling by follistatin. The EMBO journal, 25(5), 1035 - 1045. doi:10.1038/sj.emboj.7601000
    • Ohta K, Kuriyama S, Okafuji T, Gejima R, Ohnuma S, Tanaka H (2006). Tsukushi cooperates with Vg1 to activate primitive streak and Hensen’s node formation in the chick embryo. Development, 133(19), 3777 - 3786.
    • Kuriyama S, Lupo G, Ohta K, Ohnuma S, Harris WA, Tanaka H (2006). Tsukushi controls ectodermal patterning and neural crest specification in Xenopus by direct regulation of BMP4 and X-delta-1 activity. Development, 133(1), 75 - 88. doi:10.1242/dev.02178
    • Ohnuma S (2006). Role of CDK inhibitors in neural cell fate determination and differentiation. Brain Science Review, , 51 - 66.
    • Vernon AE, Movassagh M, Horan I, Wise H, Ohnuma S, Philpott A (2006). Notch targets the Cdk inhibitor Xic1 to regulate differentiation but not the cell cycle in neurons. EMBO Reports, 7(6), 643 - 648. doi:10.1038/sj.embor.7400691


    • Ohta K, Kuriyama S, Okafuji T, Gejima R, Ohnuma S, Tanaka H (2005). Tsukushi is involved in the primitive streak formation in cooperation with Vg1. MECHANISMS OF DEVELOPMENT, 122, S78 - S78.
    • Ohnuma S, Morris-Triggs SA, Daniels M, Mochizuki T, Shimizu K, Zorn AM (2005). Role of PIAS family members in Xenopus mesoderm induction. MECHANISMS OF DEVELOPMENT, 122, S165 - S165.
    • Philpott A, Vernon AE, Ohnuma S (2005). The cyclin-dependent kinase inhibitor Xic1 is a mediator of lateral inhibition during primary neurogenesis. MECHANISMS OF DEVELOPMENT, 122, S25 - S25.
    • Ohta K, Ohnuma S (2005). Molecular mechanism of chick early development: The new entry of Tsukushi. Cell Technology, 24(7), 722 - 728.


    • Daniels M, Dhokia V, Richard-Parpaillon L, Ohnuma S (2004). Identification of Xenopus cyclin-dependent kinase inhibitors, p16Xic2 and p17Xic3. Gene, 342(1), 41 - 47.
    • Daniels M, Shimizu K, Zorn AM, Ohnuma S (2004). Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm formation. development, 131(22), 5613 - 5626. doi:10.1242/dev.01449
    • Ohta K, Lupo G, Kuriyama S, Keynes R, Holt CE, Harris WA, Tanaka H, Ohnuma S (2004). Tsukushi functions as an organizer inducer by inhibition of BMP activity in cooperation with chordin. Developmental Cell, 7(3), 347 - 358. doi:10.1016/j.devcel.2004.08.014


    • Ohnuma S, Harris WA (2003). Neurogenesis and the cell cycle. neuron, 40(2), 199 - 208. doi:10.1016/S0896-6273(03)00632-9
    • Cremiso F, Philpott A, Ohnuma S (2003). Cell cycle and cell fate interaction in neural development.. Current Opinion in Neurobiology, 13, 26 - 33.


    • Ohnuma S, Hopper S, Wang KC, Philpott A, Harris WA (2002). Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina. Development, 129(10), 2435 - 2446.
    • Ohnuma SM, F B, S P, M H, W A (2002). Lipofection strategy for the study of Xenopus retinal development. Methods, 28(4), 411 - 419.


    • Ohnuma S, Philpott A, Harris WA (2001). Cell cycle and cell fate in the nervous system.. Curr Opin Neurobiol, 11(1), 66 - 73.


    • Hirooka K, Ohnuma S, Koike-Takeshita A, Koyama T, Nishino T (2000). Mechanism of product chain length determination for heptaprenyl diphosphate synthase from Bacillus stearothermophilus.. Eur J Biochem, 267(14), 4520 - 4528.
    • Wang KC, Ohnuma S (2000). Isoprenyl diphosphate synthases. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1529(1-3), 33 - 48. doi:10.1016/S1388-1981(00)00136-0


    • Wang K, Ohnuma S (1999). Chain-length determination mechanism of isoprenyl diphosphate synthases and implications for molecular evolution. TRENDS IN BIOCHEMICAL SCIENCES, 24(11), 445 - 451. doi:10.1016/S0968-0004(99)01464-4
    • Narita K, Ohnuma S, Nishino T (1999). Protein design of geranyl diphosphate synthase. Structural features that define the product specificities of prenyltransferases.. J Biochem, 126(3), 566 - 571.
    • Ohnuma S, Philpott A, Wang K, Holt CE, Harris WA (1999). p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina.. Cell, 99(5), 499 - 510.
    • Ruchhoeft ML, Ohnuma S, McNeill L, Holt CE, Harris WA (1999). The neuronal architecture of Xenopus retinal ganglion cells is sculpted by rho-family GTPases in vivo. JOURNAL OF NEUROSCIENCE, 19(19), 8454 - 8463.


    • Ohto C, Nakane H, Obata S, Hemmi H, Ohnuma S-I, Nishino T (1998). Overexpression of an Archaeal Geranylgeranyl Diphosphate Synthase in Escherichia coli Cells. Bioscience, Biotechnology and Biochemistry, 62(6), 1243 - 1246.
    • Ohnuma S, Hirooka K, Tsuruoka N, Yano M, Ohto C, Nakane H, Nishino T (1998). A pathway where polyprenyl diphosphate elongates in prenyltransferase. Insight into a common mechanism of chain length determination of prenyltransferases.. J Biol Chem, 273(41), 26705 - 26713.
    • Hemmi H, Ohnuma S, Nagaoka K, Nishino T (1998). Identification of genes affecting lycopene formation in Escherichia coli transformed with carotenoid biosynthetic genes: candidates for early genes in isoprenoid biosynthesis.. J Biochem, 123(6), 1088 - 1096.
    • Ohnuma S, Hemmi H, Koyama T, Ogura K, Nishino T (1998). Recognition of allylic substrates in Sulfolobus acidocaldarius geranylgeranyl diphosphate synthase: analysis using mutated enzymes and artificial allylic substrates.. J Biochem, 123(6), 1036 - 1040.


    • Ohnuma S, Hemmi H, Ohto C, Nakane H, Nishino T (1997). Effects of random mutagenesis in a putative substrate-binding domain of geranylgeranyl diphosphate synthase upon intermediate formation and substrate specificity.. J Biochem, 121(4), 696 - 704.
    • Ohnuma SI, Hirooka K, Ohto C, Nishino T (1997). Conversion from archaeal geranylgeranyl diphosphate synthase to farnesyl diphosphate synthase. Two amino acids before the first aspartate-rich motif solely determine eukaryotic farnesyl diphosphate synthase activity.. J Biol Chem, 272(8), 5192 - 5198.


    • Fujisaki S, Horiuchi T, Takahashi I, Tsukui S, Nishimura Y, Ohnuma S, Nishino T, Kitabatake M, Inokuchi H (1996). Cloning of a gene from Escherichia coli that confers resistance to fosmidomycin as a consequence of amplification. Gene, 175(1-2), 83 - 87. doi:10.1016/0378-1119(96)00128-X
    • Ohnuma SI, Narita K, Nakazawa T, Ishida C, Takeuchi Y, Ohto C, Nishino T (1996). A role of the amino acid residue located on the fifth position before the first aspartate-rich motif of farnesyl diphosphate synthase on determination of the final product.. J Biol Chem, 271(48), 30748 - 30754.
    • Ohnuma S, Hirooka K, Hemmi H, Ishida C, Ohto C, Nishino T (1996). Conversion of product specificity of archaebacterial geranylgeranyl-diphosphate synthase. Identification of essential amino acid residues for chain length determination of prenyltransferase reaction.. J Biol Chem, 271(31), 18831 - 18837.
    • Ohnuma S, Nakazawa T, Hemmi H, Hallberg AM, Koyama T, Ogura K, Nishino T (1996). Conversion from farnesyl diphosphate synthase to geranylgeranyl diphosphate synthase by random chemical mutagenesis.. J Biol Chem, 271(17), 10087 - 10095.
    • Ohnuma S, Watanabe M, Nishino T (1996). Identification and characterization of geranylgeraniol kinase and geranylgeranyl phosphate kinase from the Archaebacterium Sulfolobus acidocaldarius.. J Biochem, 119(3), 541 - 547.


    • Ohnuma S, Suzuki M, Nishino T (1994). Archaebacterial ether-linked lipid biosynthetic gene. Expression cloning, sequencing, and characterization of geranylgeranyl-diphosphate synthase.. J Biol Chem, 269(20), 14792 - 14797.


    • Ohnuma S-I, Koyama T, Ogura K (1993). Solanesyl diphosphate synthase reaction with artificial substrates. Formation of R and S-enantiomers of 4- and 8- methyl derivatives of geranylgeranyl diphosphate. Bioorganic and Medicinal Chemistry Letters, 3(12), 2733 - 2738. doi:10.1016/S0960-894X(01)80754-X
    • Ohnuma S, Koyama T, Ogura K (1993). Alteration of the product specificities of prenyltransferases by metal ions.. Biochem Biophys Res Commun, 192(2), 407 - 412. doi:10.1006/bbrc.1993.1430


    • Ohnuma S, Koyama T, Ogura K (1992). Chain length distribution of the products formed in solanesyl diphosphate synthase reaction.. J Biochem, 112(6), 743 - 749.


    • Ohnuma S, Koyama T, Ogura K (1991). Purification of solanesyl-diphosphate synthase from Micrococcus luteus. A new class of prenyltransferase.. J Biol Chem, 266(35), 23706 - 23713.
    • Ohnuma S-I, Koyama T, Ogura K (1991). Enzymatic synthesis of glycinoprenols. Tetrahedron Letters, 32(2), 241 - 242. doi:10.1016/0040-4039(91)80865-4


    • Koyama T, Inoue H, Ohnuma S-I, Ogura K (1990). Prenyltransferase reaction involving enantiomeric discrimination. Enzymatic synthesis of (S)-10, 11-epoxyfarnesol from racemic 6, 7-epoxygeranyl diphosphate and isopentenyl dipnosphate. Tetrahedron Letters, 31(29), 4189 - 4190. doi:10.1016/S0040-4039(00)97578-6


    • Ohnuma S, Koyama T, Ogura K (1989). Kinetic studies on the prenyl chain elongation by undecaprenyl diphosphate synthase with artificial substrate homologues.. FEBS Lett, 257(1), 71 - 74.
    • Ohnuma S-I, Ito M, Koyama T, Ogura K (1989). Undecaprenyl diphosphate synthase reaction with artificial substrate homologues - novel behavior in the termination of prenyl chain elongation. Tetrahedron, 45(19), 6145 - 6160. doi:10.1016/S0040-4020(01)85127-9


    • Koyama T, Ito M, Ohnuma S-I, Ogura K (1988). Novel behavior of undecaprenyl diphosphate synthase toward an artificial substrate. Formation of the S-4-methyl derivative ofz,e,e,-geranylgeranyl diphosphate. Tetrahedron Letters, 29(31), 3807 - 3810. doi:10.1016/S0040-4039(00)82120-6


    • Kato T, Yamaguchi Y, Ohnuma S-I, Uyehara T, Namai T, Kodama M, Shiobara Y (1986). Structural elucidation of 11-hydroxy-12,13-epoxyoctadeca-(9Z,15Z)-dienoic acids from rice plants suffering from rice blast disease. Journal of the Chemical Society, Chemical Communications, (10), 743 - 744.

    • Bilitou A, De Marco N, Bello AM, Garzia L, Carotenuto P, Kim M, Campanella C, Ohnuma S, Zollo M (). Spatial and temporal expressions of prune reveal a role in Muller gliogenesis during Xenopus retinal development. Gene, 509(1), 93 - 103. doi:10.1016/j.gene.2012.08.001