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Georg Halder

Present Title & Affiliation

Primary Appointment

Associate Professor, Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Research Interests

 How do organs know when to stop growing?

(Growth control, regeneration, tumor suppressor genes, Drosophila genetics)

 Growth is fundamental to development, yet remarkably little is known about the mechanisms that control organ size. How do cells know when to stop dividing after an organ has reached its proper size and how do injured organs regenerate missing or damaged parts? The answers to these questions are currently not known, but a common theme appears to be that cells signal to each other to regulate cell proliferation and organ growth. What are these signals and how do they regulate organ growth? We are using the fruit fly Drosophila as a model system to address these questions and to discover novel signaling pathways that regulate growth and regeneration. The combination of the powerful genetic tools and the capability of its developing tissues to regenerate make Drosophila a superb system in which to study growth control and regeneration.

 To discover novel growth control genes we carried out several genome-wide genetic screens through which we discovered a novel growth control pathway that we named the “Hippo pathway”. We and others identified several components of the Hippo pathway and it turns out that the Hippo pathway is a novel signal transduction pathway from the membrane receptor Fat over the Hippo kinase into the nucleus where the pathway regulates gene expression. Importantly, animals carrying mutations in Hippo pathway components develop severely overgrown structures and have tumorous outgrowths. The Hippo pathway is thus essential to regulate normal organ size. Strikingly, the Hippo pathway is highly conserved in vertebrates where it also regulates growth and is involved in cancer. However, how the Hippo pathway is regulated and what role it plays during normal growth and regeneration is not known. We are currently investigating novel extracellular signals that regulate the Hippo pathway and how Hippo signaling and other pathways are involved in the control of organ growth and regeneration.  

Office Address

The University of Texas M. D. Anderson Cancer Center
1515 Holcombe Blvd.
Unit Number: 1000
Houston, TX 77030
Room Number: S11.8316A
Phone: 713 834-6288
Fax: 713 834-6266
Email: ghalder@mdanderson.org

Education & Training

Degree-Granting Education

1996 University of Basel, Basel, Switzerland, PHD, Cell and Developmental Biology
1990 University of Basel, Switzerland, BS, Molecular Biology

Postgraduate Training

1996-2000 Research Fellowship, University of Wisconsin, Madison, WI, Dr. Sean Carroll

Selected Publications

Peer-Reviewed Original Research Articles
1. Hamaratoglu F, Gajewski K, Sansores-Garcia L, Morrison C, Tao C, and Halder G. The Hippo tumor suppressor pathway regulates apical domain size in parallel to tissue growth. J Cell Science 122(14), 2009.
2. Papa R, Morrison CM, Walters JR, Counterman BA, Chen R, Halder G, Ferguson L, Chamberlain N, Ffrench-Constant R, Kapan DD, Jiggins CD, Reed RD, McMillan WO. Highly conserved gene order and numerous novel repetitive elements in genomic regions linked to wing pattern variation in Heliconius butterflies. BMC Genomics 22(9):345, 7/2008.
3. Willecke M, Hamaratoglu F, Sansores-Garcia L, Tao C, Halder G. Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation. Proc Nat'l Acad Sci USA 105(39):14897-902, 2008.
4. Chamilos G, Lewis RE, Hu J, Xiao L, Zal T, Gilliet M, Halder G, Kontoyiannis DP. Drosophila melanogaster as a model host to dissect the immunopathogenesis of zygomycosis. Proc Nat'l Acad Sci USA 105(27):9367-72, 2008.
5. Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, Xie J, Ikenoue T, Yu J, Li L, Zheng P, Ye K, Chinnaiyan A, Halder G, Lai ZC, Guan KL. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes & Development 21:2747-61, 2007.
6. Childress JL, Acar M, Tao C, Halder G. Lethal giant discs, a novel C2-domain protein, restricts notch activation during endocytosis. Curr Biol 16:2228-33, 11/2006. PMID: 17088062.
7. Willecke M, Hamaratoglu F, Kango-Singh M, Udan R, Chen CL, Tao C, Zhang X, Halder G. The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size. Curr Biol 16:2090-100, 11/2006. PMID: 16996265.
8. Nolo R, Morrison CM, Tao C, Zhang X, Halder G. The bantam microRNA is a target of the hippo tumor-suppressor pathway. Curr Biol 16:1895-904, 10/2006. PMID: 16949821.
9. Chamilos G, Lionakis MS, Lewis RE, Lopez-Ribot JL, Saville SP, Albert ND, Halder G, Kontoyiannis DP. Drosophila melanogaster as a facile model for large-scale studies of virulence mechanisms and antifungal drug efficacy in Candida species. J Infect Dis 193(7):1014-22, 4/2006. PMID: 16518764.
10. Anbanandam A, Albarado DC, Nguyen CT, Halder G, Gao X. Veeraraghavan S. Insights into Transcription Enhancer Factor 1 (TEF-1) Activity From The Solution Structure of the TEA Domain. Proc Natl Acad Sci USA 103:17225-30, 2006.
11. Hamaratoglu F, Willecke M, Kango-Singh M, Nolo R, Hyun E, Tao C, Jafar-Nejad H, Halder G. The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. Nat Cell Biol 8(1):27-36, 2006. PMID: 16341207.
12. Eder AM, Sui X, Rosen DG, Nolden LK, Cheng KW, Lahad JP, Kango-Singh M, Lu KH, Warneke CL, Atkinson EN, Bedrosian I, Keyomarsi K, Kuo WL, Gray JW, Yin JC, Liu J, Halder G, Mills GB. Atypical PKC iota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc Natl Acad Sci U S A 102(35):12519-24, 8/2005. PMID: 16116079.
13. Lionakis MS, Lewis RE, May GS, Wiederhold NP, Albert ND, Halder G, Kontoyiannis DP. Toll-deficient Drosophila flies as a fast, high-throughput model for the study of antifungal drug efficacy against invasive aspergillosis and Aspergillus virulence. J Infect Dis 191(7):1188-95, 4/2005. PMID: 15747256.
14. Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nat Cell Biol 5(10):914-20, 10/2003. PMID: 14502294.
15. Kango-Singh M, Nolo R, Tao C, Verstreken P, Hiesinger PR, Bellen HJ, Halder G. Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila. Development 129(24):5719-30, 12/2002. PMID: 12421711.
16. Halder G, Carroll SB. Binding of the Vestigial co-factor switches the DNA-target selectivity of the Scalloped selector protein. Development 128(17):3295-305, 9/2001. PMID: 11546746.
17. Nussbaumer U, Halder G, Groppe J, Affolter M, Montagne J. Expression of the blistered/DSRF gene is controlled by different morphogens during Drosophila trachea and wing development. Mech Dev 96(1):27-36, 8/2000. PMID: 10940622.
18. Lewis DL, DeCamillis MA, Brunetti CR, Halder G, Kassner VA, Selegue JE, Higgs S, Carroll SB. Ectopic gene expression and homeotic transformations in arthropods using recombinant Sindbis viruses. Curr Biol 9(22):1279-87, 11/1999. PMID: 10574759.
19. Czerny T, Halder G, Kloter U, Souabni A, Gehring WJ, Busslinger M. twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol Cell 3(3):297-307, 3/1999. PMID: 10198632.
20. Chen R, Halder G, Zhang Z, Mardon G. Signaling by the TGF-beta homolog decapentaplegic functions reiteratively within the network of genes controlling retinal cell fate determination in Drosophila. Development 126(5):935-43, 2/1999. PMID: 9927595.
21. Weatherbee SD, Nijhout HF, Grunert LW, Halder G, Galant R, Selegue J, Carroll S. Ultrabithorax function in butterfly wings and the evolution of insect wing patterns. Curr Biol 9(3):109-15, 2/1999. PMID: 10021383.
22. Halder G, Polaczyk P, Kraus ME, Hudson A, Kim J, Laughon A, Carroll S. The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila. Genes Dev 12(24):3900-9, 12/1998. PMID: 9869643.
23. Halder G, Callaerts P, Flister S, Walldorf U, Kloter U, Gehring WJ. Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125(12):2181-91, 6/1998. PMID: 9584118.
24. Weatherbee SD, Halder G, Kim J, Hudson A, Carroll S. Ultrabithorax regulates genes at several levels of the wing-patterning hierarchy to shape the development of the Drosophila haltere. Genes Dev 12(10):1474-82, 5/1998. PMID: 9585507.
25. Tomarev SI, Callaerts P, Kos L, Zinovieva R, Halder G, Gehring W, Piatigorsky J. Squid Pax-6 and eye development. Proc Natl Acad Sci U S A 94(6):2421-6, 3/1997. PMID: 9122210.
26. Glardon S, Callaerts P, Halder G, Gehring WJ. Conservation of Pax-6 in a lower chordate, the ascidian Phallusia mammillata. Development 124(4):817-25, 2/1997. PMID: 9043063.
27. Halder G, Callaerts P, Gehring WJ. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267(5205):1788-92, 3/1995. PMID: 7892602.
28. Arber S, Halder G, Caroni P. Muscle LIM protein, a novel essential regulator of myogenesis, promotes myogenic differentiation. Cell 79(2):221-31, 10/1994. PMID: 7954791.

Invited Articles
1. Childress, J, Behringer, R, GHalder. Learning to Fly: Phenotypic markers in Drosophila. Poster produced with Genesis, 2005.
2. Kango-Singh M, Halder G. Drosophila as an emerging model to study metastasis. Genome Biol 5(4):216, 2004. PMID: 15059249.
3. Curtiss J, Halder G, Mlodzik M. Selector and signalling molecules cooperate in organ patterning. Nat Cell Biol 4(3):E48-51, 3/2002. PMID: 11875444.
4. Halder G and Paddock S. Presentation of Confocal Images In Confocal Microscopy Methods and Protocols. Humana Press:373-384, 1998.
5. Callaerts P, Halder G, Gehring WJ. PAX-6 in development and evolution. Annu Rev Neurosci 20:483-532, 1997. PMID: 9056723.
6. Halder G, Callaerts P, Gehring WJ. New perspectives on eye evolution. Curr Opin Genet Dev 5(5):602-9, 10/1995. PMID: 8664548.

Last updated: 6/29/2009