Tiffany Cook , Ph.D.

Molecular basis of eye development; retinal degenerative diseases; photoreceptor biology; cell-specific transcriptional regulatory mechanisms; evolutionary conservation of retina and lens formation between vertebrates and invertebrates; Drosophila genetics

Our lab is focused on understanding the molecular basis of normal eye development, and how these processes are disrupted in disease states.  For this, we take advantage of the fruit fly Drosophila melanogaster, a system that allows us to readily combine cellular, molecular, biochemical, and genetic approaches to dissect transcriptional events underlying cell type specification in various ocular tissues.  Our studies have revealed that many of the same factors involved in retinogenesis and lens formation in the fly are also necessary for vertebrate eye development.  For instance, Crx in humans is a transcription factor implicated in retinal degenerative diseases such as retinitis pigmentosa (RP), Leber amaurosis, and cone-rod dystrophy, and is important for controlling a wide range of processes necessary for the differentiation of different photoreceptor subtypes.   Crx is highly similar to the Drosophila protein Otd, and like Crx, Otd is critical for many aspects of photoreceptor differentiation.   Therefore, our studies on Otd and Crx will help address many basic developmental questions related to how different retinal cell types develop, and should aid efforts to develop therapies against otherwise blinding human diseases.  Similarly, our studies on fly lens development have provided some of the first evidence that lens development is conserved between vertebrate camera-like eyes and invertebrate compound eyes.   These functions in part involve the transcription factor Prospero.   Since Prospero has recently been identified as a tumor suppressor and is critical for neural stem cell maintenance, our work should not only impact our studying diseases that affect lens function, such as cataracts, but should also serve as a useful model for  better understanding the role of Prospero-related factors during neural development and cancer.

Areas of research include:
1.  Photoreceptor subtype specification:  Different retinal degenerative diseases affect distinct photoreceptor populations.  We are uncovering photoreceptor-specific pathways in the fly eye as a means to understand mechanisms underlying retinal degeneration. 

2.  Cell-specific gene expression: Opsins are required for visual input and to prevent retinal degeneration.  Using the regulatory sequences of the opsins as molecular tool, we have found several factors involved in retina development and function.

3.  Molecular control of lens development: We are studying how signaling pathways and downstream target transcription factors coordinate processes necessary for lens formation.  Interestingly, these studies also have implications for processes related to cancer biology.

Grant: #SRS 001741 Investigators:Cook, Tiffany 01-01-2005 -12-31-2008 Research to Prevent Blindness, Inc. Research to Prevent Blindness Career Development Award Role:PI $200,000.00 Closed Level:Private Non-Profit

Peer Reviewed Publications

Charlton-Perkins, Mark; Whitaker, S Leigh; Fei, Yueyang; Xie, Baotong; Li-Kroeger, David; Gebelein, Brian; Cook, Tiffany (2011. ) Prospero and Pax2 combinatorially control neural cell fate decisions by modulating Ras- and Notch-dependent signaling.Neural development, , 6 (1 ) ,20 More Information

Gutzwiller, Lisa M; Witt, Lorraine M; Gresser, Amy L; Burns, Kevin A; Cook, Tiffany A; Gebelein, Brian (2010. ) Proneural and abdominal Hox inputs synergize to promote sensory organ formation in the Drosophila abdomen.Developmental biology, , 348 (2 ) ,231-43 More Information

Rajkumar, Premraj; Rollmann, Stephanie M; Cook, Tiffany A; Layne, John E (2010. ) Molecular evidence for color discrimination in the Atlantic sand fiddler crab, Uca pugilator.The Journal of experimental biology, , 213 (Pt 24 ) ,4240-8 More Information

McDonald, Elizabeth C; Xie, Baotong; Workman, Michael; Charlton-Perkins, Mark; Terrell, David A; Reischl, Joachim; Wimmer, Ernst A; Gebelein, Brian A; Cook, Tiffany A (2010. ) Separable transcriptional regulatory domains within Otd control photoreceptor terminal differentiation events.Developmental biology, , 347 (1 ) ,122-32 More Information

Mishra, Monalisa; Oke, Ashwini; Lebel, Cindy; McDonald, Elizabeth C; Plummer, Zachary; Cook, Tiffany A; Zelhof, Andrew C (2010. ) Pph13 and orthodenticle define a dual regulatory pathway for photoreceptor cell morphogenesis and function.Development (Cambridge, England), , 137 (17 ) ,2895-904 More Information

Witt, Lorraine M; Gutzwiller, Lisa M; Gresser, Amy L; Li-Kroeger, David; Cook, Tiffany A; Gebelein, Brian (2010. ) Atonal, Senseless, and Abdominal-A regulate rhomboid enhancer activity in abdominal sensory organ precursors.Developmental biology, , 344 (2 ) ,1060-70 More Information

Phelan, James D; Shroyer, Noah F; Cook, Tiffany; Gebelein, Brian; Grimes, H Leighton (2010. ) Gfi1-cells and circuits: unraveling transcriptional networks of development and disease.Current opinion in hematology, , 17 (4 ) ,300-7 More Information

Uhl, Juli D; Cook, Tiffany A; Gebelein, Brian (2010. ) Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements.Developmental biology, , 343 (1-2 ) ,154-66 More Information

Charlton-Perkins, Mark; Cook, Tiffany A (2010. ) Building a fly eye: terminal differentiation events of the retina, corneal lens, and pigmented epithelia.Current topics in developmental biology, , 93 ,129-73 More Information

Lomberk, Gwen A; Imoto, Issei; Gebelein, Brian; Urrutia, Raul; Cook, Tiffany A (2010. ) Conservation of the TGFbeta/Labial homeobox signaling loop in endoderm-derived cells between Drosophila and mammals.Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], , 10 (1 ) ,74-84 More Information

Maksimovic, Srdjan; Cook, Tiffany A; Buschbeck, Elke K (2009. ) Spatial distribution of opsin-encoding mRNAs in the tiered larval retinas of the sunburst diving beetle Thermonectus marmoratus (Coleoptera: Dytiscidae).The Journal of experimental biology, , 212 (Pt 23 ) ,3781-94 More Information

Li-Kroeger, David; Witt, Lorraine M; Grimes, H Leighton; Cook, Tiffany A; Gebelein, Brian (2008. ) Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS.Developmental cell, , 15 (2 ) ,298-308 More Information

Mazzoni, Esteban O; Celik, Arzu; Wernet, Mathias F; Vasiliauskas, Daniel; Johnston, Robert J; Cook, Tiffany A; Pichaud, Franck; Desplan, Claude (2008. ) Iroquois complex genes induce co-expression of rhodopsins in Drosophila.PLoS biology, , 6 (4 ) ,e97 More Information

Ranade, Swati S; Yang-Zhou, Donghui; Kong, Sek Won; McDonald, Elizabeth C; Cook, Tiffany A; Pignoni, Francesca (2008. ) Analysis of the Otd-dependent transcriptome supports the evolutionary conservation of CRX/OTX/OTD functions in flies and vertebrates.Developmental biology, , 315 (2 ) ,521-34 More Information

Jackowska, Magdalena; Bao, Riyue; Liu, Zhenyi; McDonald, Elizabeth C; Cook, Tiffany A; Friedrich, Markus (2007. ) Genomic and gene regulatory signatures of cryptozoic adaptation: Loss of blue sensitive photoreceptors through expansion of long wavelength-opsin expression in the red flour beetle Tribolium castaneum.Frontiers in zoology, , 4 ,24 More Information

Xie, Baotong; Charlton-Perkins, Mark; McDonald, Elizabeth; Gebelein, Brian; Cook, Tiffany (2007. ) Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila.Development (Cambridge, England), , 134 (23 ) ,4243-53 More Information

Neve, Bernadette; Fernandez-Zapico, Martin E; Ashkenazi-Katalan, Vered; Dina, Christian; Hamid, Yasmin H; Joly, Erik; Vaillant, Emmanuel; Benmezroua, Yamina; Durand, Emmanuelle; Bakaher, Nicolas; Delannoy, Valerie; Vaxillaire, Martine; Cook, Tiffany; Dallinga-Thie, Geesje M; Jansen, Hans; Charles, Marie-Aline; Clément, Karine; Galan, Pilar; Hercberg, Serge; Helbecque, Nicole; Charpentier, Guillaume; Prentki, Marc; Hansen, Torben; Pedersen, Oluf; Urrutia, Raul; Melloul, Danielle; Froguel, Philippe (2005. ) Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function.Proceedings of the National Academy of Sciences of the United States of America, , 102 (13 ) ,4807-12 More Information

Cao, Sheng; Fernandez-Zapico, Martin E; Jin, Dongzu; Puri, Vishwajeet; Cook, Tiffany A; Lerman, Lilach O; Zhu, Xiang-Yang; Urrutia, Raul; Shah, Vijay (2005. ) KLF11-mediated repression antagonizes Sp1/sterol-responsive element-binding protein-induced transcriptional activation of caveolin-1 in response to cholesterol signaling.The Journal of biological chemistry, , 280 (3 ) ,1901-10 More Information

Cook, Tiffany (2003. ) Cell diversity in the retina: more than meets the eye.BioEssays : news and reviews in molecular, cellular and developmental biology, , 25 (10 ) ,921-5 More Information

Tahayato, Ali; Sonneville, Remi; Pichaud, Franck; Wernet, Mathias F; Papatsenko, Dmitri; Beaufils, Philippe; Cook, Tiffany; Desplan, Claude (2003. ) Otd/Crx, a dual regulator for the specification of ommatidia subtypes in the Drosophila retina. Developmental cell, , 5 (3 ) ,391-402

Cook, Tiffany; Pichaud, Franck; Sonneville, Remi; Papatsenko, Dmitri; Desplan, Claude (2003. ) Distinction between color photoreceptor cell fates is controlled by Prospero in Drosophila. Developmental cell, , 4 (6 ) ,853-64

Kaczynski, Joanna; Cook, Tiffany; Urrutia, Raul (2003. ) Sp1- and Krüppel-like transcription factors. Genome biology, , 4 (2 ) ,206

Li-Kroeger, David; Cook, Tiffany A; Gebelein, Brian (2012. ) Integration of an abdominal Hox complex with Pax2 yields cell-specific EGF secretion from Drosophila sensory precursor cells.Development (Cambridge, England), , 139 (9 ) ,1611-9 More Information

Terrell, David; Xie, Baotong; Workman, Michael; Mahato, Simpla; Zelhof, Andrew; Gebelein, Brian; Cook, Tiffany (2012. ) OTX2 and CRX rescue overlapping and photoreceptor-specific functions in the Drosophila eye.Developmental dynamics : an official publication of the American Association of Anatomists, , 241 (1 ) ,215-28 More Information

Charlton-Perkins, Mark; Brown, Nadean L; Cook, Tiffany A (2011. ) The lens in focus: a comparison of lens development in Drosophila and vertebrates.Molecular genetics and genomics : MGG, , 286 (3-4 ) ,189-213 More Information

Johnston, Robert J; Otake, Yoshiaki; Sood, Pranidhi; Vogt, Nina; Behnia, Rudy; Vasiliauskas, Daniel; McDonald, Elizabeth; Xie, Baotong; Koenig, Sebastian; Wolf, Reinhard; Cook, Tiffany; Gebelein, Brian; Kussell, Edo; Nakagoshi, Hideki; Desplan, Claude (2011. ) Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye.Cell, , 145 (6 ) ,956-68 More Information

Cook, T; Urrutia, R (2000. ) TIEG proteins join the Smads as TGF-beta-regulated transcription factors that control pancreatic cell growth. American journal of physiology. Gastrointestinal and liver physiology, , 278 (4 ) ,G513-21

Cook, T; Gebelein, B; Belal, M; Mesa, K; Urrutia, R (1999. ) Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins. The Journal of biological chemistry, , 274 (41 ) ,29500-4

Cook, T; Gebelein, B; Urrutia, R (1999. ) Sp1 and its likes: biochemical and functional predictions for a growing family of zinc finger transcription factors. Annals of the New York Academy of Sciences, , 880 ,94-102

Cook, T; Gebelein, B; Mesa, K; Mladek, A; Urrutia, R (1998. ) Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth. The Journal of biological chemistry, , 273 (40 ) ,25929-36

Urrutia, R; Henley, J R; Cook, T; McNiven, M A (1997. ) The dynamins: redundant or distinct functions for an expanding family of related GTPases? .Proceedings of the National Academy of Sciences of the United States of America, , 94 (2 ) ,377-84

Cook, T A; Mesa, K J; Gebelein, B A; Urrutia, R A (1996. ) Upregulation of dynamin II expression during the acquisition of a mature pancreatic acinar cell phenotype. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, , 44 (12 ) ,1373-8

Cook, T; Mesa, K; Urrutia, R (1996. ) Three dynamin-encoding genes are differentially expressed in developing rat brain. Journal of neurochemistry, , 67 (3 ) ,927-31

Mesa, K; Gebelein, B; Cook, T; Urrutia, R (1996. ) Identification and characterization of zinc finger encoding genes from the tumoral exocrine pancreatic cell line AR42J. Cancer letters, , 103 (2 ) ,143-9

Valentich, M A; Cook, T; Urrutia, R (1996. ) Expression of dynamin immunoreactivity in experimental pancreatic tumors induced in rat by mancozeb-nitrosomethylurea. Cancer letters, , 102 (1-2 ) ,23-9

Cook, T A; Urrutia, R; McNiven, M A (1994. ) Identification of dynamin 2, an isoform ubiquitously expressed in rat tissues. Proceedings of the National Academy of Sciences of the United States of America, , 91 (2 ) ,644-8

Drosophila, genetics, photoreceptor, retina, eye, lens, transcription, cell fate

Please contact Dr. Cook using the email account:  tiffany.cook@cchmc.org,

Academic - Cincinnati Children's Hospital Medical Center
3333 Burnet Ave, MLC 7003
Cincinnati  Ohio, 45229
Phone: 513-636-6991
tiffany.cook@cchmc.org