Faculty Profile

Professional Summary:

My lab is interested in how global gene expression advances from one state to the next in time and space during development to promote the specification and differentiation of individual retinal cell types from multi-potent neural progenitor cells. We focus on the gene regulatory network (GRN) involved in the formation of one retinal cell type, retinal ganglion cells (RGCs). RGCs are the only projection neurons in the retina and connect the retina to the brain through the optic nerve. Death of RGCs is cause of vision loss in glaucoma and other retinal diseases. Several key transcription factors (TFs) functioning at different stages of RGC development have been identified; Math5 is essential for RGC fate specification, whereas Pou4f2 and Isl1 are required for their differentiation. Our previous study has established a tentative model for the RGC GRN, in which these TFs occupy key node positions. Current projects in the lab are aimed at further understanding how these transcription factors specifically regulate their target genes and how they interact with each other. Considerable efforts are also placed on identifying novel key regulators in the GRN. Our studies employ a combined approach of genetics, genomics and bioinformatics. Our eventual goal is to use the knowledge learned from our studies to develop new therapies for various retinal diseases.

Education and Training:

PhD, Biochemistry and Molecular Biology, Peking Union Medical College (1994)
MD, Medicine, Qingdao Medical College (1989)

Employment:

Associate Professor, Ophthalmology, University at Buffalo, School of Medicine and Biological Sciences (2015-present)
Assistant Professor, Ophthalmology, University at Buffalo, School of Medicine and Biological Sciences (2008–2015)
Assistant Professor, Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center (2003–2008)
Instructor, Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center (2002–2003)
Postdoctoral Associate, Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center (1999–2001)
Postdoctoral Fellow, National Institutes of Health (1994–1999)

Grants and Sponsored Research:

February 2010–December 2013
Biological Response to Change in Air Quality Pre-, Mid-, Post-Olympics
NIH/NIEHS
Role: Principal Investigator
$848,133
Interaction of Isl1 and Pou4f2 in retinal development
National Institutes of Health
Role: Principal Investigator
$1,250,000

Journal Articles:

Wu F, Kaczynski TJ, Sethuramanujam S, Li R, Jain V, Slaughter M, Mu X. Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate. Proc Natl Acad Sci U S A. 2015; 112(13).
Gao Z, Mao CA, Pan P, Mu X, Klein WH. Transcriptome of Atoh7 retinal progenitor cells identifies new Atoh7-dependent regulatory genes for retinal ganglion cell formation. Dev Neurobiol. 2014; 74(11).
Sapkota D, Chintala H, Wu F, Fliesler SJ, Hu Z, Mu X. Onecut1 and Onecut2 redundantly regulate early retinal cell fates during development. Proc Natl Acad Sci U S A. 2014; 111(39).
Li R, Wu F, Ruonala R, Sapkota D, Hu Z, Mu X. Isl1 and Pou4f2 form a complex to regulate target genes in developing retinal ganglion cells. PLoS One. 2014; 9(3).
Shi M, Kumar SR, Motajo O, Kretschmer F, Mu X, Badea TC. Genetic interactions between Brn3 transcription factors in retinal ganglion cell type specification. PLoS One. 2013; 8(10).
Ehrman LA, Mu X, Waclaw RR, Yoshida Y, Vorhees CV, Klein WH, Campbell K. The LIM homeobox gene Isl1 is required for the correct development of the striatonigral pathway in the mouse. Proc Natl Acad Sci U S A. 2013; 110(42).
Wu F, Li R, Umino Y, Kaczynski TJ, Sapkota D, Li S, Xiang M, Fliesler SJ, Sherry DM, Gannon M, Solessio E, Mu X. Onecut1 Is Essential for Horizontal Cell Genesis and Retinal Integrity. J Neurosci. 2013; 33(32).
Wu F, Sapkota D, Li R, Mu X. Onecut 1 and Onecut 2 are potential regulators of mouse retinal development. J Comp Neurol. 2012; 520(5).
Edwards MM, McLeod DS, Li R, Grebe R, Bhutto I, Mu X, Lutty GA. The deletion of Math5 disrupts retinal blood vessel and glial development in mice. Exp Eye Res. 2012; 96(1).
Sapkota D, Wu F, Mu X. Focus on Molecules: Math5 and retinal ganglion cells. Exp Eye Res. 2011; 93(6).
Kiyama T, Mao CA, Cho JH, Fu X, Pan P, Mu X, Klein WH. Overlapping spatiotemporal patterns of regulatory gene expression are required for neuronal progenitors to specify retinal ganglion cell fate. Vision Res. 2011; 51(2).
Fu X, Kiyama T, Li R, Russell M, Klein WH, Mu X. Epitope-tagging Math5 and Pou4f2: new tools to study retinal ganglion cell development in the mouse. Dev Dyn. 2009; 238(9).
Cho JH, Mu X, Wang SW, Klein WH. Retinal ganglion cell death and optic nerve degeneration by genetic ablation in adult mice. Exp Eye Res. 2009; 88(3).
Sapieha P, Sirinyan M, Hamel D, Zaniolo K, Joyal JS, Cho JH, Honoré JC, Kermorvant-Duchemin E, Varma DR, Tremblay S, Leduc M, Rihakova L, Hardy P, Klein WH, Mu X, Mamer O, Lachapelle P, Di Polo A, Beauséjour C, Andelfinger G, Mitchell G, Sennlaub F, Chemtob S. The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis. Nat Med. 2008; 14(10).
Mu X, Fu X, Beremand PD, Thomas TL, Klein WH. Gene regulation logic in retinal ganglion cell development: Isl1 defines a critical branch distinct from but overlapping with Pou4f2. Proc Natl Acad Sci U S A. 2008; 105(19).
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 N, Murray G, Wang D, Mellott D, Olinski R, Hallböök F, Thorndyke MC. A genomic view of the sea urchin nervous system. Dev Biol. 2006; 300(1).
Fu X, Sun H, Klein WH, Mu X. Beta-catenin is essential for lamination but not neurogenesis in mouse retinal development. Dev Biol. 2006; 299(2).
Sodergren E, Weinstock GM, Davidson EH, Cameron RA, Gibbs RA, Angerer RC, Angerer LM, Arnone MI, Burgess DR, Burke RD, Coffman JA, Dean M, Elphick MR, Ettensohn CA, Foltz KR, Hamdoun A, Hynes RO, Klein WH, Marzluff W, McClay DR, Morris RL, Mushegian A, Rast JP, Smith LC, Thorndyke MC, Vacquier VD, Wessel GM, Wray G, Zhang L, Elsik CG, Ermolaeva O, Hlavina W, Hofmann G, Kitts P, Landrum MJ, Mackey AJ, Maglott D, Panopoulou G, Poustka AJ, Pruitt K, Sapojnikov V, Song X, Souvorov A, Solovyev V, Wei Z, Whittaker CA, Worley K, Durbin KJ, Shen Y, Fedrigo O, Garfield D, Haygood R, Primus A, Satija R, Severson T, Gonzalez-Garay ML, Jackson AR, Milosavljevic A, Tong M, Killian CE, Livingston BT, Wilt FH, Adams N, Bellé R, Carbonneau S, Cheung R, Cormier P, Cosson B, Croce J, Fernandez-Guerra A, Genevière AM, Goel M, Kelkar H, Morales J, Mulner-Lorillon O, Robertson AJ, Goldstone JV, Cole B, Epel D, Gold B, Hahn ME, Howard-Ashby M, Scally M, Stegeman JJ, Allgood EL, Cool J, Judkins KM, McCafferty SS, Musante AM, Obar RA, Rawson AP, Rossetti BJ, Gibbons IR, Hoffman MP, Leone A, Istrail S, Materna SC, Samanta MP, Stolc V, Tongprasit W, Tu Q, Bergeron KF, Brandhorst BP, Whittle J, Berney K, Bottjer DJ, Calestani C, Peterson K, Chow E, Yuan QA, Elhaik E, Graur D, Reese JT, Bosdet I, Heesun S, Marra MA, Schein J, Anderson MK, Brockton V, Buckley KM, Cohen AH, Fugmann SD, Hibino T, Loza-Coll M, Majeske AJ, Messier C, Nair SV, Pancer Z, Terwilliger DP, Agca C, Arboleda E, Chen N, Churcher AM, Hallböök F, Humphrey GW, Idris MM, Kiyama T, Liang S, Mellott D, Mu X, Murray G, Olinski RP, Raible F, Rowe M, Taylor JS, Tessmar-Raible K, Wang D, Wilson KH, Yaguchi S, Gaasterland T, Galindo BE, Gunaratne HJ, Juliano C, Kinukawa M, Moy GW, Neill AT, Nomura M, Raisch M, Reade A, Roux MM, Song JL, Su YH, Townley IK, Voronina E, Wong JL, Amore G, Branno M, Brown ER, Cavalieri V, Duboc V, Duloquin L, Flytzanis C, Gache C, Lapraz F, Lepage T, Locascio A, Martinez P, Matassi G, Matranga V, Range R, Rizzo F, Röttinger E, Beane W, Bradham C, Byrum C, Glenn T, Hussain S, Manning G, Miranda E, Thomason R, Walton K, Wikramanayke A, Wu SY, Xu R, Brown CT, Chen L, Gray RF, Lee PY, Nam J, Oliveri P, Smith J, Muzny D, Bell S, Chacko J, Cree A, Curry S, Davis C, Dinh H, Dugan-Rocha S, Fowler J, Gill R, Hamilton C, Hernandez J, Hines S, Hume J, Jackson L, Jolivet A, Kovar C, Lee S, Lewis L, Miner G, Morgan M, Nazareth LV, Okwuonu G, Parker D, Pu LL, Thorn R, Wright R. The genome of the sea urchin Strongylocentrotus purpuratus. Science. 2006; 314(5801).
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. 2005; 280(2).
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. 2005; 15(6).
Martin SE, Mu X, Klein WH. Identification of an N-terminal transcriptional activation domain within Brn3b/POU4f2. Differentiation. 2005; 73(1).
Liang S, Zhao S, Mu X, Thomas T, Klein WH. Novel retinal genes discovered by mining the mouse embryonic RetinalExpress database. Mol Vis. 2004; 10.
Mu X, Beremand PD, Zhao S, Pershad R, Sun H, Scarpa A, Liang S, Thomas TL, Klein WH. Discrete gene sets depend on POU domain transcription factor Brn3b/Brn-3.2/POU4f2 for their expression in the mouse embryonic retina. Development. 2004; 131(6).
Mu X, Klein WH. A gene regulatory hierarchy for retinal ganglion cell specification and differentiation. Semin Cell Dev Biol. 2004; 15(1).
Fortunel NO, Otu HH, Ng HH, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA, Hatzfeld A, Usta F, Vega VB, Long PM, Libermann TA, Lim B. Comment on " ‘Stemness‘: transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature". Science. 2003; 302(5644).
Wang SW, Mu X, Bowers WJ, Klein WH. Retinal ganglion cell differentiation in cultured mouse retinal explants. Methods. 2002; 28(4).
Wang SW, Mu X, Bowers WJ, Kim DS, Plas DJ, Crair MC, Federoff HJ, Gan L, Klein WH. Brn3b/Brn3c double knockout mice reveal an unsuspected role for Brn3c in retinal ganglion cell axon outgrowth. Development. 2002; 129(2).
Mu X, Zhao S, Pershad R, Hsieh TF, Scarpa A, Wang SW, White RA, Beremand PD, Thomas TL, Gan L, Klein WH. Gene expression in the developing mouse retina by EST sequencing and microarray analysis. Nucleic Acids Res. 2001; 29(24).
Mu X, Spanos SA, Shiloach J, Kimmel A. CRTF is a novel transcription factor that regulates multiple stages of Dictyostelium development. Development. 2001; 128(13).
Mu X, Lee B, Louis JM, Kimmel AR. Sequence-specific protein interaction with a transcriptional enhancer involved in the autoregulated expression of cAMP receptor 1 in Dictyostelium. Development. 1998; 125(18).

Xiuqian Mu PhD

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