Hyung Don Ryoo

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Hyung Don Ryoo, Ph.D., D.Phil.

Associate Professor; Advsr Cellular Molecular Bio Trng Program; Co Dir CMB Training Program; Inst Lecturer-Cell Bio & Histology
Department of Cell Biology (Cell Biology)

Contact Info

550 First Avenue
Floor 4 Room 497B
Medical Science Building
New York, NY 10016


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1994-2000 — Columbia Univ, Graduate Education

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Research Summary

Our laboratory is interested in understanding the basic mechanisms of apoptosis during animal development and in diseases. Our strategy is to use the genetic and cell biological tools of Drosophila as a model system.

Apoptosis is a morphologically distinct form of cell death that is programmed to sculpt body structures, maintain proper numbers of cells during development and eliminate damaged and potentially dangerous cells. Apoptosis is found defective in most cancers, and excess apoptosis underlies many neurodegenerative disorders. A critical event in apoptosis is the activation caspases, a family member of the Cysteine proteases that reside in living cells as inactive zymogens and activated in cells that undergo apoptosis. For proper apoptosis regulation, caspases are extensively regulated, both through its activators such as Apaf-1/cytochrome c and through its inhibitors such as IAPs (Inhibitor of Apoptosis Proteins). In Drosophila, various cell death stimuli converge on the transcriptional and post-transcriptional regulation of IAP inhibitors Reaper, Hid and Grim.

Our research program can be subdivided into two major areas. Our first area of interest is to understand the mechanism of caspase regulation. We have previously demonstrated that Drosophila IAP1 (DIAP1) acts as a ubiquitin-ligase that targets apical caspase Dronc in living cells, and undergoes auto-ubiquitylation during apoptosis (Ryoo et. al., 2002; Ryoo et. al., 2004). Furthermore, we showed that DIAP1 inhibition, which occurs in cells doomed to die, leads to the induction of secretory factors DPP and WG. In turn, these secreted factors promote the proliferation and growth of neighboring cells. We have proposed that this regulatory mechanism contributes to apoptosis-induced compensatory cell proliferation (Ryoo et. al., 2004). We plan to further investigate the mechanistic basis of coordination between apoptosis and cell proliferation with a special focus on Diap1 and caspases. Progress in this area may enhance our understanding of how tissue size is regulated during animal development and in cancer (Ryoo et. al., 2003).

Our second research program is aimed at understanding how endoplasmic stress (ER-stress) activates apoptosis. ER-stress is frequently caused by unfolded proteins in the ER, and is thought to be the cause of a wide variety of disorders, including alzheimer's disease, parkinson's disease, retinitis pigmentosa, multiple myeloma and diabetes. Although apoptosis is a pathologically relevant outcome of ER-stress, how caspases become activated under these conditions remains poorly characterized. We have begun investigating the Drosophila genes that make up the cellular response machinery to ER-stress, also known as the Unfolded Protein Response (UPR). Through this effort, we found that the Drosophila xbp1 mRNA undergoes unconventional splicing in response to ER-stress, similar to those found in other organisms. This property was used to generate an ER-stress sensor where GFP is expressed in frame only after xbp1 mRNA splicing. Significantly, xbp1 splicing and ER-chaperone induction occurs in the Drosophila model for the Autosomal Dominant Retinitis Pigmentosa (ADRP), where the expression of mutant rhodopsin-1 molecules leads to late onset retinal degeneration. These developments provide a basis to investigate how ER-stress activates apoptosis in Drosophila disease models (Ryoo et. al., 2007). Ongoing efforts aim to examine existing hypotheses and to identify new components linking ER-stress and caspase activation.

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All data from NYU Health Sciences Library Faculty Bibliography — -


Integration of UPRER and Oxidative Stress Signaling in the Control of Intestinal Stem Cell Proliferation
Wang, Lifen; Zeng, Xiankun; Ryoo, Hyung Don; Jasper, Heinrich
2014 Aug;10(8):e1004568-e1004568 e1004568, PLoS genetics
— id: 1162622, year: 2014, vol: 10, page: e1004568, stat: Journal Article,

Hyperactivated Wnt Signaling Induces Synthetic Lethal Interaction with Rb Inactivation by Elevating TORC1 Activities
Zhang, Tianyi; Liao, Yang; Hsu, Fu-Ning; Zhang, Robin; Searle, Jennifer S; Pei, Xun; Li, Xuan; Ryoo, Hyung Don; Ji, Jun-Yuan; Du, Wei
2014 May;10(5):e1004357-e1004357 e1004357, PLoS genetics
— id: 968252, year: 2014, vol: 10, page: e1004357, stat: Journal Article,

Xbp1-independent Ire1 signaling is required for photoreceptor differentiation and rhabdomere morphogenesis in Drosophila
Coelho, Dina S; Cairrao, Fatima; Zeng, Xiaomei; Pires, Elisabete; Coelho, Ana V; Ron, David; Ryoo, Hyung Don; Domingos, Pedro M
2013 Nov;5(3):791-801, Cell reports
— id: 700742, year: 2013, vol: 5, page: 791, stat: Journal Article,

Drosophila p53 isoforms differentially regulate apoptosis and apoptosis-induced proliferation
Dichtel-Danjoy, M-L; Ma, D; Dourlen, P; Chatelain, G; Napoletano, F; Robin, M; Corbet, M; Levet, C; Hafsi, H; Hainaut, P; Ryoo, H D; Bourdon, J-C; Mollereau, B
2013 Jan;20(1):108-116, Cell death & differentiation
— id: 206302, year: 2013, vol: 20, page: 108, stat: Journal Article,

Compensatory proliferation and apoptosis-induced proliferation: a need for clarification
Mollereau, B; Perez-Garijo, A; Bergmann, A; Miura, M; Gerlitz, O; Ryoo, H D; Steller, H; Morata, G
2013 Jan;20(1):181-181, Cell death & differentiation
— id: 206292, year: 2013, vol: 20, page: 181, stat: Journal Article,

CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid
Morishita, Jun; Kang, Min-Ji; Fidelin, Kevin; Ryoo, Hyung Don
2013 Dec;5(6):1481-1488, Cell reports
— id: 759772, year: 2013, vol: 5, page: 1481, stat: Journal Article,

Drosophila XBP1 Expression Reporter Marks Cells under Endoplasmic Reticulum Stress and with High Protein Secretory Load
Ryoo, Hyung Don; Li, Josepher; Kang, Min-Ji
2013 ;8(9):e75774-e75774 e75774, PLoS one
— id: 574142, year: 2013, vol: 8, page: e75774, stat: Journal Article,

A modified UPR stress sensing system reveals a novel tissue distribution of IRE1/XBP1 activity during normal Drosophila development
Sone, Michio; Zeng, Xiaomei; Larese, Joseph; Ryoo, Hyung Don
2013 May;18(3):307-319, Cell stress chaperones
— id: 304812, year: 2013, vol: 18, page: 307, stat: Journal Article,

Expression of human Gaucher disease gene GBA generates neurodevelopmental defects and ER stress in Drosophila eye
Suzuki, Takahiro; Shimoda, Masami; Ito, Kumpei; Hanai, Shuji; Aizawa, Hidenobu; Kato, Tomoki; Kawasaki, Kazunori; Yamaguchi, Terumi; Ryoo, Hyung Don; Goto-Inoue, Naoko; Setou, Mitsutoshi; Tsuji, Shoji; Ishida, Norio
2013 ;8(8):e69147-e69147 e69147, PLoS one
— id: 761512, year: 2013, vol: 8, page: e69147, stat: Journal Article,

Drosophila BRUCE inhibits apoptosis through non-lysine ubiquitination of the IAP-antagonist REAPER
Domingues, C; Ryoo, H D
2012 Mar;19(3):470-477, Cell death & differentiation
— id: 158637, year: 2012, vol: 19, page: 470, stat: Journal Article,

CDK5 and MEKK1 mediate pro-apoptotic signalling following endoplasmic reticulum stress in an autosomal dominant retinitis pigmentosa model
Kang, Min-Ji; Chung, Jaehoon; Ryoo, Hyung Don
2012 Apr;14(4):409-415, Nature cell biology
— id: 163572, year: 2012, vol: 14, page: 409, stat: Journal Article,

Pro-apoptotic signaling pathway by CDK5 and MEKK1
Ryoo, Hyung Don
2012 May;11(9):1746-1747, Cell cycle
— id: 166825, year: 2012, vol: 11, page: 1746, stat: Journal Article,

The role of apoptosis-induced proliferation for regeneration and cancer
Ryoo, Hyung Don; Bergmann, Andreas
2012 ;4(8):a008797-a008797, Cold Spring Harbor perspectives in biology
— id: 174400, year: 2012, vol: 4, page: a008797, stat: Journal Article,

Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response
Malzer, Elke; Daly, Marie-Louise; Moloney, Aileen; Sendall, Timothy J; Thomas, Sally E; Ryder, Edward; Ryoo, Hyung Don; Crowther, Damian C; Lomas, David A; Marciniak, Stefan J
2010 Sep;123(Pt 17):2892-2900, Journal of cell science
— id: 761532, year: 2010, vol: 123, page: 2892, stat: Journal Article,

Distinct death mechanisms in Drosophila development
Ryoo, Hyung Don; Baehrecke, Eric H
2010 Dec;22(6):889-895, Current opinion in cell biology
— id: 761522, year: 2010, vol: 22, page: 889, stat: Journal Article,

Drosophila IAP antagonists form multimeric complexes to promote cell death
Sandu, Cristinel; Ryoo, Hyung Don; Steller, Hermann
2010 Sep 20;190(6):1039-1052, Journal of cell biology
— id: 133803, year: 2010, vol: 190, page: 1039, stat: Journal Article,

Suppression of retinal degeneration in Drosophila by stimulation of ER-associated degradation
Kang, Min-Ji; Ryoo, Hyung Don
2009 Oct 6;106(40):17043-17048, Proceedings of the National Academy of Sciences of the United States of America
— id: 104349, year: 2009, vol: 106, page: 17043, stat: Journal Article,

ER stress protects from retinal degeneration
Mendes, Cesar S; Levet, Clemence; Chatelain, Gilles; Dourlen, Pierre; Fouillet, Antoine; Dichtel-Danjoy, Marie-Laure; Gambis, Alexis; Ryoo, Hyung Don; Steller, Hermann; Mollereau, Bertrand
2009 May;28(9):1296-1307, EMBO journal
— id: 761552, year: 2009, vol: 28, page: 1296, stat: Journal Article,

Hyung Don Ryoo: a healthy career in cellular death
Ryoo, Hyung Don
2009 Jun;185(5):758-759, Journal of cell biology
— id: 761542, year: 2009, vol: 185, page: 758, stat: Journal Article,

STAT92E is a positive regulator of Drosophila inhibitor of apoptosis 1 (DIAP/1) and protects against radiation-induced apoptosis
Betz, Aurel; Ryoo, Hyung Don; Steller, Hermann; Darnell, James E Jr
2008 Sep 16;105(37):13805-13810, Proceedings of the National Academy of Sciences of the United States of America
— id: 90753, year: 2008, vol: 105, page: 13805, stat: Journal Article,

Regulation of the Drosophila apoptosome through feedback inhibition
Shapiro, Peter J; Hsu, Hans H; Jung, Heekyung; Robbins, Edith S; Ryoo, Hyung Don
2008 Dec;10(12):1440-1446, Nature cell biology
— id: 90751, year: 2008, vol: 10, page: 1440, stat: Journal Article,

Ero1L, a thiol oxidase, is required for Notch signaling through cysteine bridge formation of the Lin12-Notch repeats in Drosophila melanogaster
Tien, An-Chi; Rajan, Akhila; Schulze, Karen L; Ryoo, Hyung Don; Acar, Melih; Steller, Hermann; Bellen, Hugo J
2008 Sep 22;182(6):1113-1125, Journal of cell biology
— id: 90752, year: 2008, vol: 182, page: 1113, stat: Journal Article,

Unfolded protein response in a Drosophila model for retinal degeneration
Ryoo, Hyung Don; Domingos, Pedro M; Kang, Min-Ji; Steller, Hermann
2007 Jan 10;26(1):242-252, EMBO journal
— id: 70029, year: 2007, vol: 26, page: 242, stat: Journal Article,

Unfolded protein response in Drosophila: why another model can make it fly
Ryoo, Hyung Don; Steller, Hermann
2007 Apr;6(7):830-835, Cell cycle
— id: 71606, year: 2007, vol: 6, page: 830, stat: Journal Article,

Developmental apoptosis
Ryoo HD; Steller H
Apoptosis in health and disease : clinical and therapeutic aspects Cambridge ; New York : Cambridge University Press, 2005,
— id: 3621, year: 2005, vol: , page: ?, stat: Chapter,

Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways
Ryoo, Hyung Don; Gorenc, Travis; Steller, Hermann
2004 Oct;7(4):491-501, Developmental cell
— id: 57966, year: 2004, vol: 7, page: 491, stat: Journal Article,

Hippo and its mission for growth control
Ryoo, Hyung Don; Steller, Hermann
2003 Oct;5(10):853-855, Nature cell biology
— id: 57967, year: 2003, vol: 5, page: 853, stat: Journal Article,

Specificity of Distalless repression and limb primordia development by abdominal Hox proteins
Gebelein, Brian; Culi, Joaquim; Ryoo, Hyung Don; Zhang, Wen; Mann, Richard S
2002 Oct;3(4):487-498, Developmental cell
— id: 57968, year: 2002, vol: 3, page: 487, stat: Journal Article,

Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1
Ryoo, Hyung Don; Bergmann, Andreas; Gonen, Hedva; Ciechanover, Aaron; Steller, Hermann
2002 Jun;4(6):432-438, Nature cell biology
— id: 57969, year: 2002, vol: 4, page: 432, stat: Journal Article,

Regulation of Hox downstream target genes by Hox/Exd/Hth
Ryoo, Hyung Don
[S.l. : s.n.], 2000,
— id: 1939, year: 2000, vol: , page: , stat: ,

Control of the nuclear localization of Extradenticle by competing nuclear import and export signals
Abu-Shaar M; Ryoo HD; Mann RS
1999 Apr 15;13(8):935-945, Genes & development
— id: 57972, year: 1999, vol: 13, page: 935, stat: Journal Article,

Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex
Passner JM; Ryoo HD; Shen L; Mann RS; Aggarwal AK
1999 Feb 25;397(6721):714-719, Nature
— id: 57973, year: 1999, vol: 397, page: 714, stat: Journal Article,

The control of trunk Hox specificity and activity by Extradenticle
Ryoo HD; Mann RS
1999 Jul 1;13(13):1704-1716, Genes & development
— id: 57971, year: 1999, vol: 13, page: 1704, stat: Journal Article,

Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex
Ryoo HD; Marty T; Casares F; Affolter M; Mann RS
1999 Nov;126(22):5137-5148, Development
— id: 57970, year: 1999, vol: 126, page: 5137, stat: Journal Article,

Switching the in vivo specificity of a minimal Hox-responsive element
Chan SK; Ryoo HD; Gould A; Krumlauf R; Mann RS
1997 May;124(10):2007-2014, Development
— id: 57977,