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William H Klein, PhD

Present Title & Affiliation

Primary Appointment

Chairman, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX
Professor, Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Houston, TX

Research Interests

Research Interests

  • Embryo development
  • Transcription factors in development
  • Control of gene expression
  • Cell fate specification and differentiation
  • Gene regulatory networks

Research Synopsis
Differentiated cells arise from progenitor cells capable of giving rise to multiple cell types. We investigate how gene expression programs are controlled as progenitor cells differentiate into specific cell types. In one project, we identify the key transcription factors that regulate the differentiation of ganglion cells in the neural retina. Retinal ganglion cells are responsible for transmitting electrical impulses to the brain via the optic nerve. Although retinal ganglion cells are essential for vision, how they form and why they die in retinal disease is poorly understood. Several transcription factors are critically positioned within a retinal ganglion cell gene regulatory network. We aim to elaborate this network. We have used genetic ablation to generate a mouse model for optic nerve degeneration, which will be valuable in attempts to repair damaged retinas.

In a second project, we investigate the transcription factor myogenin during skeletal muscle growth and repair. We have mouse models in which we can remove the myogenin gene during embryonic and adult life. Myogenin is essential for initial muscle differentiation and also has functions in muscle growth and repair. We aim to understand how myogenin exerts these critical functions.

Office Address

The University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd.
Unit Number: 1000
Houston, TX 77030
Room Number: S9.8336C
Phone: 713 834-6301
Fax: 713 834-6266
Email: whklein@mdanderson.org

Education & Training

Degree-Granting Education

1973 University of Illinois, Urbana, IL, PHD, Biochemistry

Selected Publications

Peer-Reviewed Original Research Articles

1. Tang H, Marvin M, Macpherson P, Mardon G, Meadows E, Klein WH, Yang XJ, Goldman D. An HDAC4/myogenin positive feedback loop coordinates denervation-dependent gene induction and repression in adult skeletal muscle. Mol Biol Cell 20(4):1120-1131, 2009.
2. Agca C, Klein WH, Venuti JM. Ectoderm specification is altered in cobalt and nickel treated sea urchin embryos. Mech Dev 126(5-6):430-442, 2009.
3. Fu X, Kiyama T, Mao CA, Li R, Russell M, Klein WH, Mu X. Epitope-tagging Math5 and Pou4f2: new tools to study retinal ganglion cell development on the mouse. Dev Dyn 238(9):2309-2317, 2009.
4. Cho JH, Mu X, Wang SW, Klein WH. Induction of optic nerve degeneration in an adult mouse by genetic ablation. Exp Eye Res 88(3):542-552, 2009.
5. Kiyama T, Zhang J, Liang S, Shen Y, Liang S, Sodergren E, Klein WH. Intragenomic evolution of a transcriptional enhancer in the genome of Strongylocentrotus purpuratus. Mar Genomics 2(2):85-98, 2009.
6. Agca C, Klein WH, Venuti JM. Reduced O(2) and elevated ROS in sea urchin embryos leads to defects in ectoderm differentiation. Dev Dyn 238(7):1777-1787, 2009.
7. Mao CA, Kiyama T, Pan P, Furuta Y, Klein WH. Eomesodermin is a target gene of Pou4f2 required for retinal ganglion cell and optic nerve development in the mouse. Development 135(2):271-280, 2008.
8. Mu X, Fu X, Beremand PD, Thomas TL, Klein WH. Gene regulation logic in retinal ganglion cell development: lsl1 defines a critical branch distinct from but overlapping with Pou4f2. Proc Natl Acad Sci USA 105(19):6942-6947, 2008.
9. Meadows E, Cho JH, Flynn JM, Klein WH. Myogenin regulates a distinct genetic program in adult muschle stem cells. Dev Biol 322(2):406-414, 2008.
10. Mao CA, Wang SW, Pan P, Klein WH. Rewiring the retinal ganglion cell gene regulatory network: Neurod1 promotes retinal ganglion cell fate in the absence of Math5. Development 135(20):3379-3388, 2008.
11. Sessa A, Mao CA, Hadjantonakis AK, Klein WH, Broccoli V. Tbr2 dictates conversion of radial glia into intermediate precursors and neuronal cell amplification promoted by indirect neurogenesis in the developing cerebral cortex. Neuron 60(1):56-69, 2008.
12. Sapieha P, Sirinyan M, Hamel D, Zaniolo K, Cho JH, Joyal JS, Honore JC, Kermorvant-Duchemin E, Varma DR, Tremblay S, Ledue M, Rihakova L, Hardy P, Klein WH, Mamer O, DiPolo A, Beausejour C, Mitchell G, Andelfinger G, Sennlaub F, Chemtob S. The succinate receptor GPR91 in neurons plays a major role in retinal angiogenesis. Nat Med 14(10):1067-1076, 2008.
13. Ali D, Fu S, Wang J, Lu MF, Chen L, Baldini A, Klein, WH, Martin JF. Canonical Wnt-signaling functions in second heart field to promote right ventricular growth. Pro Natl Acad Sci USA 104(22):9319-9324, 2007.
14. Cho JH, Klein WH, Tsai MJ. Compensational regulation of bHLH transcription factors in the postnatal development of BETA2/NeuroD1-null retina. Mec Dev 124(7-8):543-550, 2007.
15. Rishniw M, Fisher, PW, Doran RM, Meadows E, Klein WH, Kotlikoff MI. Smooth muscle persists in the muscularis externa of developing and adult mouse esophagus. J Muscle Res Cell Motil 28(2-3):153-165, 2007.
16. Kiyama T, Klein WH. SpGataE, a Strongylocentrotus purpuratus ortholog of mammalian Gata4/5: protein expression, interaction with target gene spec2a, and identification of friend of Gata factor SpFog1. Dev Genes Evol 217(9):651-663, 2007.
17. Davie JK, Cho JH, Meadows E, Knapp JR, Flynn JM, Klein WH. Target gene selectivity for the myogenic basic helix-loop-helix transcription factor myogenin. Dev Biol 311(2):650-654, 2007.
18. Burke RD, Angerer LM, Elphick MR, Humphrey GW, Yaguchi S, Kiyama T, Liang S, Mu X, Agca C, Klein WH, Brandhorst BP, Rowe M, Wilson K, Churcher AM, Taylor JS, Chen J, Murray G, Wang D, Mellon D, Hallook F, Olinski R, Thorndyke MC. A genomic view of the sea urchin nervous system. Dev Biol 300(1):434-460, 2006.
19. Fu X, Sun H, Klein WH, Mu X. b-catenin is essential for lamination but not neurogenesis in mouse retinal development. Dev Biol 299:424-37, 2006. PMID: 16959241.
20. Knapp JR, Davie JK, Myer A, Meadows E, Olson EN, Klein WH. Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size. Development 133(4):601-10, 2006. PMID: 16407395.
21. Sea Urchin Genome Sequencing Consortium. The genome of the sea urchin strongylocentrotus Purpuratus. Science 314(5801):941-952, 2006.
22. Mu X, Fu X, Sun H, Beremand PD, Thomas TL, Klein WH. A gene network downstream of transcription factor Math5 regulates retinal progenitor cell competence and ganglion cell fate. Dev Biol 280(2):467-81, 2005. PMID: 15882586.
23. Mu X, Fu X, Sun H, Liang S, Maeda H, Frishman LJ, Klein WH. Ganglion cells are required for normal progenitor- cell proliferation but not cell-fate determination or patterning in the developing mouse retina. Curr Biol 15(6):525-30, 2005. PMID: 15797020.
24. Martin SE, Mu X, Klein WH. Identification of an N-terminal transcriptional activation domain within Brn3b/POU4f2. Differentiation 73(1):18-27, 2005. PMID: 15733064.
25. Kiyama T, Zhang N, Dayal S, Yun Lee P, Liang S, Villinski JT, Klein WH. Strongylocentrotus purpuratus transcription factor GATA-E binds to and represses transcription at an Otx-Goosecoid cis-regulatory element within the aboral ectoderm-specific spec2a enhancer. Dev Biol 280(2):436-47, 2005. PMID: 15882584.
26. Villinski JT, Kiyama T, Dayal S, Zhang N, Liang S, Klein WH. Structure, expression, and transcriptional regulation of the Strongylocentrotus franciscanus spec gene family encoding intracellular calcium-binding proteins. Dev Genes Evol 215(8):410-22, 2005. PMID: 15871032.
27. Dayal S, Kiyama T, Villinski JT, Zhang N, Liang S, Klein WH. Creation of cis-regulatory elements during sea urchin evolution by co-option and optimization of a repetitive sequence adjacent to the spec2a gene. Dev Biol 273(2):436-53, 2004. PMID: 15328024.
28. Liang S, Zhao S, Mu X, Thomas T, Klein WH. Novel retinal genes discovered by mining the mouse embryonic RetinalExpress database. Mol Vis 10:773-86, 2004. PMID: 15496829.

Last updated: 1/8/2013