headshot of Kun Che Chang

Kun Che Chang

Assistant Professor
KCCHANG@pitt.edu
(412) 647-2342
Lab web Google Scholar Bioengineering Department

overview

Glaucoma and other optic neuropathies lead to damage and eventual cell death of retinal ganglion cells (RGCs). Once lost, RGCs are not replaced in humans or other mammals, resulting in irreversible blindness. Gene therapy via viral infection in retinas is the potential treatment for restoring degenerating cells and axons. Understanding regulatory mechanism of gene therapy in neuronal regeneration suggests a potent therapeutic 
strategy for vision restoration in optic neuropathies. 
On the other hand, transplantation of stem cell-derived RGCs could be a feasible approach to restore vision; however, it is not well understood how to promote RGC differentiation from stem cells (SCs). Thus, identifying the relevant signaling pathways that promote RGC specification will be necessary to generate donor RGCs that integrate and form functional connections within recipient retinas. To date, several protocols have been reported for RGC generation from human SCs, however, these protocols are labor intensive, require significant time in culture, and yield low efficiencies of RGC production. To overcome these issues, I will develop a rapid differentiation protocol combing with a 3D retinal organoid model in hESCs to investigate the relevant signaling and/or transcription factors in RGC fate specification.

about

PhD, University of Colorado Anschutz Medical Campus, 2011 - 2015

MS, National Tsing Hua University, 2006 - 2008

BS, National Dong Hwa University, 2002 - 2006

Rao, M., Liu, C.C., Wang, S., & Chang, K.C. (2025). Generating ESC-Derived RGCs for Cell Replacement Therapy. Methods in Molecular Biology, 2848, 187-196.Springer Nature. doi: 10.1007/978-1-0716-4087-6_12.

Alahmari, H., Liu, C.C., Rubin, E., Lin, V.Y., Rodriguez, P., & Chang, K.C. (2024). Vitamin C alleviates hyperglycemic stress in retinal pigment epithelial cells. MOLECULAR BIOLOGY REPORTS, 51(1), 637.Springer Nature. doi: 10.1007/s11033-024-09595-2.

Cameron, E.G., Nahmou, M., Toth, A.B., Heo, L., Tanasa, B., Dalal, R., Yan, W., Nallagatla, P., Xia, X., Hay, S., Knasel, C., Stiles, T.L., Douglas, C., Atkins, M., Sun, C., Ashouri, M., Bian, M., Chang, K.C., Russano, K., Shah, S., Woodworth, M.B., Galvao, J., Nair, R.V., Kapiloff, M.S., & Goldberg, J.L. (2024). A molecular switch for neuroprotective astrocyte reactivity. NATURE, 626(7999), 574-582.Springer Nature. doi: 10.1038/s41586-023-06935-3.

Chen, T.E., Lo, J., Huang, S.P., Chang, K.C., Liu, P.L., Wu, H.E., Chen, Y.R., Chang, Y.C., Liu, C.C., Lee, P.Y., Lai, Y.H., Wu, P.C., Wang, S.C., & Li, C.Y. (2024). Glaucine inhibits hypoxia-induced angiogenesis and attenuates LPS-induced inflammation in human retinal pigment epithelial ARPE-19 cells. EUROPEAN JOURNAL OF PHARMACOLOGY, 981, 176883.Elsevier. doi: 10.1016/j.ejphar.2024.176883.

Huang, Y.K., Wang, T.M., Chen, C.Y., Li, C.Y., Wang, S.C., Irshad, K., Pan, Y., & Chang, K.C. (2024). The role of ALDH1A1 in glioblastoma proliferation and invasion. CHEMICO-BIOLOGICAL INTERACTIONS, 402, 111202.Elsevier. doi: 10.1016/j.cbi.2024.111202.

Luo, Z., & Chang, K.C. (2024). Cell replacement with stem cell-derived retinal ganglion cells from different protocols. NEURAL REGENERATION RESEARCH, 19(4), 807-810.Wolters Kluwer. doi: 10.4103/1673-5374.381494.

Luo, Z., Shah, S., Tanasa, B., Chang, K.C., & L, J.L. (2024). Article Gene regulatory roles of growth and differentiation factors in retinal development. ISCIENCE, 27(6), 110100.Elsevier. doi: 10.1016/j.isci.2024.110100.

Rao, M., & Chang, K.C. (2024). Aldose reductase is a potential therapeutic target for neurodegeneration. CHEMICO-BIOLOGICAL INTERACTIONS, 389, 110856.Elsevier. doi: 10.1016/j.cbi.2024.110856.

Wang, S., Chen, C.Y., Liu, C.C., Stavropoulos, D., Rao, M., Petrash, J.M., & Chang, K.C. (2024). GDF-15 Attenuates the Epithelium-Mesenchymal Transition and Alleviates TGFβ2-Induced β 2-Induced Lens Opacity. TRANSLATIONAL VISION SCIENCE & TECHNOLOGY, 13(7), 2.Association for Research in Vision and Ophthalmology (ARVO). doi: 10.1167/tvst.13.7.2.

Chien, H.T., Li, C.Y., Su, W.H., Chang, K.C., Chen, C.S., Liu, Y.T., Chen, C.Y., Dai, C.Y., & Wang, S.C. (2023). Multi-omics profiling of chemotactic characteristics of brain microglia and astrocytoma. LIFE SCIENCES, 330, 121855.Elsevier. doi: 10.1016/j.lfs.2023.121855.

Huang, Y.K., Chang, K.C., Li, C.Y., Lieu, A.S., & Lin, C.L. (2023). AKR1B1 Represses Glioma Cell Proliferation through p38 MAPK-Mediated Bcl-2/BAX/Caspase-3 Apoptotic Signaling Pathways. CURRENT ISSUES IN MOLECULAR BIOLOGY, 45(4), 3391-3405.MDPI. doi: 10.3390/cimb45040222.

Irshad, K., Huang, Y.K., Rodriguez, P., Lo, J., Aghoghovwia, B.E., Pan, Y., & Chang, K.C. (2023). The Neuroimmune Regulation and Potential Therapeutic Strategies of Optic Pathway Glioma. BRAIN SCIENCES, 13(10), 1424.MDPI. doi: 10.3390/brainsci13101424.

Lo, J., Mehta, K., Dhillon, A., Huang, Y.K., Luo, Z., Nam, M.H., Al Diri, I., & Chang, K.C. (2023). Therapeutic strategies for glaucoma and optic neuropathies. MOLECULAR ASPECTS OF MEDICINE, 94, 101219.Elsevier. doi: 10.1016/j.mam.2023.101219.

Lo, J., Wu, H.E., Liu, C.C., Chang, K.C., Lee, P.Y., Liu, P.L., Huang, S.P., Wu, P.C., Lin, T.C., Lai, Y.H., Chang, Y.C., Chen, Y.R., Lee, S.I., Huang, Y.K., Wang, S.C., & Li, C.Y. (2023). Nordalbergin Exerts Anti-Neuroinflammatory Effects by Attenuating MAPK Signaling Pathway, NLRP3 Inflammasome Activation and ROS Production in LPS-Stimulated BV2 Microglia. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(8), 7300.MDPI. doi: 10.3390/ijms24087300.

Ning, K., Bhuckory, M.B., Lo, C.H., Sendayen, B.E., Kowal, T.J., Chen, M., Bansal, R., Chang, K.C., Vollrath, D., Berbari, N.F., Mahajan, V.B., Hu, Y., & Sun, Y. (2023). Cilia-associated wound repair mediated by IFT88 in retinal pigment epithelium. SCIENTIFIC REPORTS, 13(1), 8205.Springer Nature. doi: 10.1038/s41598-023-35099-3.

Rao, M., Huang, Y.K., Liu, C.C., Meadows, C., Cheng, H.C., Zhou, M., Chen, Y.C., Xia, X., Goldberg, J.L., Williams, A.M., Kuwajima, T., & Chang, K.C. (2023). Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation. SCIENTIFIC REPORTS, 13(1), 5592.Springer Nature. doi: 10.1038/s41598-023-32702-5.

Chang, K.C. (2022). Influence of Sox protein SUMOylation on neural development and regeneration. NEURAL REGENERATION RESEARCH, 17(3), 477-481.Wolters Kluwer. doi: 10.4103/1673-5374.320968.

Chang, K.C., Liu, P.F., Chang, C.H., Lin, Y.C., Chen, Y.J., & Shu, C.W. (2022). The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases. CELL AND BIOSCIENCE, 12(1), 1.Springer Nature. doi: 10.1186/s13578-021-00736-9.

Huang, Y.K., Chen, Y.C., Liu, C.C., Cheng, H.C., Tu, A.T., & Chang, K.C. (2022). Cerebral Complications of Snakebite Envenoming: Case Studies. TOXINS, 14(7), 436.MDPI. doi: 10.3390/toxins14070436.

Huang, Y.K., Liu, C.C., Wang, S., Cheng, H.C., Meadows, C., & Chang, K.C. (2022). The Role of Aldose Reductase in Beta-Amyloid-Induced Microglia Activation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(23), 15088.MDPI. doi: 10.3390/ijms232315088.

Luo, Z., Chang, K.C., Wu, S., Sun, C., Xia, X., Nahmou, M., Bian, M., Wen, R.R., Zhu, Y., Shah, S., Tanasa, B., Wernig, M., & Goldberg, J.L. (2022). Directly induced human retinal ganglion cells mimic fetal RGCs and are neuroprotective after transplantation in vivo. STEM CELL REPORTS, 17(12), 2690-2703.Elsevier. doi: 10.1016/j.stemcr.2022.10.011.

Noro, T., Shah, S.H., Yin, Y., Kawaguchi, R., Yokota, S., Chang, K.C., Madaan, A., Sun, C., Coppola, G., Geschwind, D., Benowitz, L.I., & Goldberg, J.L. (2022). Elk-1 regulates retinal ganglion cell axon regeneration after injury. SCIENTIFIC REPORTS, 12(1), 17446.Springer Nature. doi: 10.1038/s41598-022-21767-3.

Chang, K.C., Bian, M., Xia, X., Madaan, A., Sun, C., Wang, Q., Li, L., Nahmou, M., Noro, T., Yokota, S., Galvao, J., Kreymerman, A., Tanasa, B., Hu, Y., & Goldberg, J.L. (2021). Posttranslational Modification of Sox11 Regulates RGC Survival and Axon Regeneration. ENEURO, 8(1), eneuro.0358-eneu20.2020.Society for Neuroscience. doi: 10.1523/ENEURO.0358-20.2020.

Chen, Y.C., Wang, T.Y., Huang, Y.K., Chang, K.C., Chen, M.H., Liu, C.C., Liu, K.L., Yang, Y.H., Yen, D.H.T., & Fan, J.S. (2021). Effects of Sodium Silicate Complex against Hemorrhagic Activities Induced by Protobothrops mucrosquamatus Venom. TOXINS, 13(1), 59.MDPI. doi: 10.3390/toxins13010059.

Ning, K., Song, E., Sendayen, B.E., Prosseda, P.P., Chang, K.C., Ghaffarieh, A., Alvarado, J.A., Wang, B., Haider, K.M., Berbari, N.F., Hu, Y., & Sun, Y. (2021). Defective INPP5E distribution in NPHP1-related Senior-Loken syndrome. MOLECULAR GENETICS & GENOMIC MEDICINE, 9(1), e1566.Wiley. doi: 10.1002/mgg3.1566.

Pan, Y., Hysinger, J.D., Barron, T., Schindler, N.F., Cobb, O., Guo, X., Yalcin, B., Anastasaki, C., Mulinyawe, S.B., Ponnuswami, A., Scheaffer, S., Ma, Y., Chang, K.C., Xia, X., Toonen, J.A., Lennon, J.J., Gibson, E.M., Huguenard, J.R., Liau, L.M., Goldberg, J.L., Monje, M., & Gutmann, D.H. (2021). NF1 mutation drives neuronal activity-dependent initiation of optic glioma. NATURE, 594(7862), 277-+.Springer Nature. doi: 10.1038/s41586-021-03580-6.

Chang, K.C., Huang, Y.K., Chen, Y.W., Chen, M.H., Tu, A.T., & Chen, Y.C. (2020). Venom Ophthalmia and Ocular Complications Caused by Snake Venom. TOXINS, 12(9), 576.MDPI. doi: 10.3390/toxins12090576.

Mohammadinejad, R., Biagioni, A., Arunkumar, G., Shapiro, R., Chang, K.C., Sedeeq, M., Taiyab, A., Hashemabadi, M., Pardakhty, A., Mandegary, A., Thiery, J.P., Aref, A.R., & Azimi, I. (2020). EMT signaling: potential contribution of CRISPR/Cas gene editing. CELLULAR AND MOLECULAR LIFE SCIENCES, 77(14), 2701-2722.Springer Nature. doi: 10.1007/s00018-020-03449-3.

Wang, Q., Zhuang, P., Huang, H., Li, L., Liu, L., Webber, H.C., Dalal, R., Siew, L., Fligor, C.M., Chang, K.C., Nahmou, M., Kreymerman, A., Sun, Y., Meyer, J.S., Goldberg, J.L., & Hu, Y. (2020). Mouse γ-Synuclein Promoter-Mediated Gene Expression and Editing in Mammalian Retinal Ganglion Cells. JOURNAL OF NEUROSCIENCE, 40(20), 3896-3914.Society for Neuroscience. doi: 10.1523/JNEUROSCI.0102-20.2020.

Xia, X., Yu, C.Y., Bian, M., Sun, C.B., Tanasa, B., Chang, K.C., Bruffett, D.M., Thakur, H., Shah, S.H., Knasel, C., Cameron, E.G., Kapiloff, M.S., & Goldberg, J.L. (2020). MEF2 transcription factors differentially contribute to retinal ganglion cell loss after optic nerve injury. In Badea, T.C. (Ed.). PLOS ONE, 15(12), e0242884.Public Library of Science (PLoS). doi: 10.1371/journal.pone.0242884.

Zhang, X., Tenerelli, K., Wu, S., Xia, X., Yokota, S., Sun, C., Galvao, J., Venugopalan, P., Li, C., Madaan, A., Goldberg, J.L., & Chang, K.C. (2020). Cell transplantation of retinal ganglion cells derived from hESCs. RESTORATIVE NEUROLOGY AND NEUROSCIENCE, 38(2), 131-140.IOS Press. doi: 10.3233/RNN-190941.

Chang, K.C., Shieh, B., & Petrash, J.M. (2019). Role of aldose reductase in diabetes-induced retinal microglia activation. CHEMICO-BIOLOGICAL INTERACTIONS, 302, 46-52.Elsevier. doi: 10.1016/j.cbi.2019.01.020.

Chang, K.C., Sun, C., Cameron, E.G., Madaan, A., Wu, S., Xia, X., Zhang, X., Tenerelli, K., Nahmou, M., Knasel, C.M., Russano, K.R., Hertz, J., & Goldberg, J.L. (2019). Opposing Effects of Growth and Differentiation Factors in Cell-Fate Specification. CURRENT BIOLOGY, 29(12), 1963-+.Elsevier. doi: 10.1016/j.cub.2019.05.011.

Kreymerman, A., Buickians, D.N., Nahmou, M.M., Tran, T., Galvao, J., Wang, Y., Sun, N., Bazik, L., Huynh, S.K., Cho, I.J., Boczek, T., Chang, K.C., Kunzevitzky, N.J., & Goldberg, J.L. (2019). MTP18 is a Novel Regulator of Mitochondrial Fission in CNS Neuron Development, Axonal Growth, and Injury Responses. SCIENTIFIC REPORTS, 9(1), 10669.Springer Nature. doi: 10.1038/s41598-019-46956-5.

Xia, X., Atkins, M., Dalal, R., Kuzmenko, O., Chang, K.C., Sun, C.B., Benatti, C.A., Rak, D.J., Nahmou, M., Kunzevitzky, N.J., & Goldberg, J.L. (2019). Magnetic Human Corneal Endothelial Cell Transplant: Delivery, Retention, and Short-Term Efficacy. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 60(7), 2438-2448.Association for Research in Vision and Ophthalmology (ARVO). doi: 10.1167/iovs.18-26001.

Chang, K.C., & Petrash, J.M. (2018). Aldo-Keto Reductases: Multifunctional Proteins as Therapeutic Targets in Diabetes and Inflammatory Disease. ALCOHOL AND CANCER, 1032(1032), 173-202.Springer Nature. doi: 10.1007/978-3-319-98788-0_13.

Wu, S., Chang, K.C., & Goldberg, J.L. (2018). Retinal Cell Fate Specification. TRENDS IN NEUROSCIENCES, 41(4), 165-167.Elsevier. doi: 10.1016/j.tins.2018.02.002.

Wu, S., Chang, K.C., Nahmou, M., & Goldberg, J.L. (2018). Induced Pluripotent Stem Cells Promote Retinal Ganglion Cell Survival After Transplant. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 59(3), 1571-1576.Association for Research in Vision and Ophthalmology (ARVO). doi: 10.1167/iovs.17-23648.

Chang, K.C., & Hertz, J. (2017). SoxC transcription factors in retinal development and regeneration. NEURAL REGENERATION RESEARCH, 12(7), 1048-1051.Wolters Kluwer. doi: 10.4103/1673-5374.211178.

Chang, K.C., Hertz, J., Zhang, X., Jin, X.L., Shaw, P., Derosa, B.A., Li, J.Y., Venugopalan, P., Valenzuela, D.A., Patel, R.D., Russano, K.R., Alshamekh, S.A., Sun, C., Tenerelli, K., Li, C., Velmeshev, D., Cheng, Y., Boyce, T.M., Dreyfuss, A., Uddin, M.S., Muller, K.J., Dykxhoorn, D.M., & Goldberg, J.L. (2017). Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development. JOURNAL OF NEUROSCIENCE, 37(19), 4967-4981.Society for Neuroscience. doi: 10.1523/JNEUROSCI.3430-13.2017.

Chang, K.C., Shieh, B., & Petrash, J.M. (2017). Influence of aldose reductase on epithelial-to-mesenchymal transition signaling in lens epithelial cells. CHEMICO-BIOLOGICAL INTERACTIONS, 276, 149-154.Elsevier. doi: 10.1016/j.cbi.2017.01.017.

Chang, K.C., Li, L., Sanborn, T.M., Shieh, B., Lenhart, P., Ammar, D., LaBarbera, D.V., & Petrash, J.M. (2016). Characterization of Emodin as a Therapeutic Agent for Diabetic Cataract. JOURNAL OF NATURAL PRODUCTS, 79(5), 1439-1444.American Chemical Society (ACS). doi: 10.1021/acs.jnatprod.6b00185.

Chang, K.C., Shieh, B., & Petrash, J.M. (2016). Aldose reductase mediates retinal microglia activation. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 473(2), 565-571.Elsevier. doi: 10.1016/j.bbrc.2016.03.122.

Chang, K.C., & Petrash, J.M. (2015). Aldose Reductase Mediates Transforming Growth Factor β2 (TGF-β2)-InducedMigration and Epithelial-To-Mesenchymal Transition of Lens-Derived Epithelial Cells. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56(8), 4198-4210.Association for Research in Vision and Ophthalmology (ARVO). doi: 10.1167/iovs.15-16557.

Chang, K.C., Snow, A., LaBarbera, D.V., & Petrash, J.M. (2015). Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells. CHEMICO-BIOLOGICAL INTERACTIONS, 234, 254-260.Elsevier. doi: 10.1016/j.cbi.2014.10.007.

Snow, A., Shieh, B., Chang, K.C., Pal, A., Lenhart, P., Ammar, D., Ruzycki, P., Palla, S., Reddy, G.B., & Petrash, J.M. (2015). Aldose reductase expression as a risk factor for cataract. CHEMICO-BIOLOGICAL INTERACTIONS, 234, 247-253.Elsevier. doi: 10.1016/j.cbi.2014.12.017.

Chang, K.C., Ponder, J., LaBarbera, D.V., & Petrash, J.M. (2014). Aldose Reductase Inhibition Prevents Endotoxin-Induced Inflammatory Responses in Retinal Microglia. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 55(5), 2853-2861.Association for Research in Vision and Ophthalmology (ARVO). doi: 10.1167/iovs.13-13487.

Li, L., Chang, K.C., Zhou, Y., Shieh, B., Ponder, J., Abraham, A.D., Ali, H., Snow, A., Petrash, J.M., & LaBarbera, D.V. (2014). Design of an Amide N-Glycoside Derivative of β-Glucogallin: A Stable, Potent, and Specific Inhibitor of Aldose Reductase. JOURNAL OF MEDICINAL CHEMISTRY, 57(1), 71-77.American Chemical Society (ACS). doi: 10.1021/jm401311d.

Chang, K.C., Laffin, B., Ponder, J., Enzsoely, A., Nemeth, J., LaBarbera, D.V., & Petrash, J.M. (2013). Beta-glucogallin reduces the expression of lipopolysaccharide-induced inflammatory markers by inhibition of aldose reductase in murine macrophages and ocular tissues. CHEMICO-BIOLOGICAL INTERACTIONS, 202(1-3), 283-287.Elsevier. doi: 10.1016/j.cbi.2012.12.001.

Wu, M.H., Tsai, Y.T., Hua, K.T., Chang, K.C., Kuo, M.L., & Lin, M.T. (2012). Eicosapentaenoic acid and docosahexaenoic acid inhibit macrophage-induced gastric cancer cell migration by attenuating the expression of matrix metalloproteinase 10. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 23(11), 1434-1439.Elsevier. doi: 10.1016/j.jnutbio.2011.09.004.

Ho, P.C., Chang, K.C., Chuang, Y.S., & Wei, L.N. (2011). Cholesterol regulation of receptor-interacting protein 140 via microRNA-33 in inflammatory cytokine production. FASEB JOURNAL, 25(5), 1758-1766.Wiley. doi: 10.1096/fj.10-179267.

Lai, C.W., Chen, K.Y., Hung, C.S., Kuo, S.W., Chang, Y.J., Lin, M.T., Chang, K.C., & Wu, M.H. (2011). Serum vascular endothelial growth factor-D levels correlate with cervical lymph node metastases in papillary thyroid carcinoma. GROWTH FACTORS, 29(2-3), 57-62.Taylor & Francis. doi: 10.3109/08977194.2011.557373.

Lu, P.H., Kuo, T.C., Chang, K.C., Chang, C.H., & Chu, C.Y. (2011). Gefitinib-induced epidermal growth factor receptor-independent keratinocyte apoptosis is mediated by the JNK activation pathway. BRITISH JOURNAL OF DERMATOLOGY, 164(1), 38-46.Oxford University Press (OUP). doi: 10.1111/j.1365-2133.2010.10038.x.

Chang, K.C., Lo, C.W., Fan, T.C., Chang, M.D.T., Shu, C.W., Chang, C.H., Chung, C.T., Fang, S.L., Chao, C.C., Tsai, J.J., & Lai, Y.K. (2010). TNF-α Mediates Eosinophil Cationic Protein-induced Apoptosis in BEAS-2B Cells. BMC CELL BIOLOGY, 11(1), 6.Springer Nature. doi: 10.1186/1471-2121-11-6.

Lo, C.W., Chang, Y.S., Chao, C.C., Chang, M.D.T., Chang, K.C., & Lai, Y.K. (2009). Control Mechanisms of Differential Translation of Hsp90 Isoforms in 9L Rat Gliosarcoma Cells. JOURNAL OF CELLULAR BIOCHEMISTRY, 107(3), 418-427.Wiley. doi: 10.1002/jcb.22138.

Chao, C.C., Sun, F.C., Wang, C.H., Lo, C.W., Chang, Y.S., Chang, K.C., Chang, M.D.T., & Lai, Y.K. (2008). Concerted actions of multiple transcription elements confer differential Transactivation of HSP90 isoforms in geldanamycin-treated 9L rat gliosarcoma cells. JOURNAL OF CELLULAR BIOCHEMISTRY, 104(4), 1286-1296.Wiley. doi: 10.1002/jcb.21705.