Department of Cell Biology and Human Anatomy, School of Medicine
A major goal of my laboratory is to understand the detailed molecular mechanisms that mediate cell-to-cell communication in vertebrates, and how errors in this crucial biological process give rise to human pathological conditions, including birth defects, tissue degeneration and cancer. Specifically, we study how the Wnt family of secreted growth factors signal via the Ror family of cell surface receptors to control polarized cell behaviors, such as migration, adhesion and changes in cell morphology. This noncanonical form of Wnt signaling, which operates independently of the classical Wnt/beta-catenin pathway, plays critical roles in early embryogenesis, nervous system development and adult tissue homeostatsis. Importantly, Ror mutations have been found to cause severe birth defects (e.g., Robinow syndrome and Brachydactyly type B), as well as several forms of metastatic cancer. Using an intersectional approach of in vivo mouse genetics and in vitro biochemical analyses, we aim to identify new components of the Wnt-Ror signaling pathway and understand how these molecules function to mediate the biological effects of this important pathway. It is our hope that by studying the Wnt-Ror signaling network, we will reveal novel principles of cell-to-cell communication and provide insights into the molecular basis of human diseases.
Morphogenetic signaling in development and disease
My lab uses a multidisciplinary approach of cell biology, biochemistry and mouse genetics to investigate key developmental pathways involved in the determination of tissue and organ shape. We are particularly interested a conserved pathway called the Wnt-Ror pathway that is implicated in the structural birth defect Robinow syndrome as well as in cancer metastasis.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
Specialties / Focus
- Cancer Biology
- Cell Biology
- Cell Division and the Cytoskeleton
- Developmental Biology
- Differentiation, Morphogenesis and Wound Healing
- Genomics, Proteomics and Metabolomics
- Molecular Genetics
- Signal Transduction
- Stem Cell Biology
- CHA 403 Medical Neuroanatomy, Summer
- BCB 210 Genetics and Genomics, Fall
Honors and Awards
- Damon Runyon Cancer Research Foundation Fellowship
- 2004 Ph.D. Cell Biology Harvard Medical School
- 1998 B.S. Biochemistry UCLA
Susman MW, Karuna EP, Kunz RC, Gujral TS, Cantú AV, Choi SS, Jong BY, Okada K, Scales MK, Hum J, Hu LS, Kirschner MW, Nishinakamura R, Yamada S, Laird DJ, Jao LE, Gygi SP, Greenberg ME, Ho HH (2017) Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates. Elife. 2017 Sep 8;6. pii: e26509. doi: 10.7554/eLife.26509. PMID:28885975
Kamizaki K, Doi R, Hayashi M, Saji T, Kanagawa M, Toda T, Fukada SI, Ho HH, Greenberg ME, Endo M, Minami Y. (2017) The Ror1 receptor tyrosine kinase plays a critical role in regulating satellite cell proliferation during regeneration of injured muscle. J Biol Chem. 2017 Sep 22;292(38):15939-15951. doi: 10.1074/jbc.M117.785709. PMID:28790171
Yuan J, Cha J, Deng W, Bartos A, Sun X, Ho HH, Borg JP, Yamaguchi TP, Yang Y, Dey SK. (2016) Planar cell polarity signaling in the uterus directs appropriate positioning of the crypt for embryo implantation. Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8079-E8088. Epub 2016 Nov 28. PMID:27911818
Arora R, Abby E, Ross AD, Cantu AV, Kissner MD, Castro V, Ho HY, Livera G, Laird DJ. (2016) Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary. J Cell Sci. 2016 Jul 1;129(13):2493-9. doi: 10.1242/jcs.189910. PMID: 27199373
Robichaux MA, Chenaux G, Ho HY, Soskis MJ, Greenberg ME, Henkemeyer M, Cowan CW. EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure (2016). Dev Neurobiol. 2016 Apr;76(4):405-20. doi: 10.1002/dneu.22323. PMID: 26148571
Cha J, Bartos, A, Park C, Sun, X, Li Y, Cha S, Ajima R, Ho HY, Yamaguchi T, Dey SK. (2014) Appropriate crypt formation in the uterus for embryo homing and implantation requires Wnt5a-ROR signaling. Cell Rep. 2014. Jul 24;8(2):382-92. doi: 10.1016/j.celrep.2014.06.027.
Robichaux MA, Chenaux G, Ho HY, Soskis MJ, Dravis C, Kwan KY, Šestan N, Greenberg ME, Henkemeyer M, Cowan CW. (2014) EphB receptor forward signaling regulates area-specific reciprocal thalamic and cortical axon pathfinding. Proc Natl Acad Sci USA. 2014 Feb 11;111(6):2188-93.
Ryu YK, Collins S, Ho HY, Zao H, Kuruvilla R. Neuron-derived Wnt5a is required for peripheral axon branching and target innervation. Dev Biol. 2013 May 1;377(1):79-89.
Soskis MJ*, Ho HY*, Bloodgood BL, Robichaux MA, Malik A, Ataman B, Rubin AA, Zieg J, Zhang C, Shokat KM, Sharma N, Cowan CW, Greenberg ME. (2012) A chemical genetic approach reveals distinct mechanisms of EphB signaling during brain development. Nat Neurosci. 2012 Dec;15(12):1645-54.
Ho HY*, Susman MW*, Bikoff JB, Ryu YK, Jonas AM, Hu L, Kuruvilla R, Greenberg ME. (2012) Wnt5a-Ror-Dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis. Proc Natl Acad Sci USA. Mar 13; 109(11):4044-51. *Equal contributions.
Margolis SS, Salogiannis J, Lipton DM, Mandel-Brehm C, Wills ZP, Mardinly AR, Hu L, Greer PL, Bikoff JB, Ho HY, Soskis MJ, Sahin M, Greenberg ME. (2010) EphB mediated degradation of the RhoA GEF Ephexin5 relieves a developmental brake on excitatory synapse formation. Cell. 2010 Oct 29;143(3):442-55.
Ma YC, Song MR, Park JP, Ho HY, Hu L, Kurtev MV, Zieg J, Ma Q, Pfaff SL, Greenberg ME. (2008) Regulation of motor neuron specification phosphorylation of neurogenin 2. Neuron 2008. Apr 10;58(1):65-77.
Zhou Z, Hong EJ, Cohen S, Zhao WN, Ho HY, Schmidt L, Chen WG, Lin Y, Savner E, Griffith EC, Hu L, Steen JA, Weitz CJ, Greenberg ME. (2006) Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron. Oct 19;52(2):255-69.
Manchanda N, Lyubimova A, Ho HY, James MF, Gusella JF, Ramesh N, Snapper SB, Ramesh V. (2005) The NF2 tumor suppressor merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function. J Biol Chem. Feb 7; 280(13):12517-22.
Ho HY*, Rohatgi R*, Lebensohn AM, Ma, L, Lee J, Gygi SP, Kirschner MW. (2004) Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. Cell, Jul 23; 118(2) 203. *Equal contributions.
Martinez-Quiles N, Ho HY, Kirschner MW, Ramesh N, Geha, RS. (2004) Erk/Src phosphorylation acts as a switch on/off mechanism that controls its ability to activate N-WASP. Molecular and Cellular Biology, Jun; 24(12)5269.
Gautreau A, Ho HY, Li J, Steen H, Gygi SP, Kirschner MW. (2004) Purification and architecture of the ubiquitous Wave complex. Proc Natl Acad Sci USA. Mar 30,101(13):4379.
Rohatgi R, Nollau P, Ho HY, Kirschner MW, Mayer BJ. (2001) Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASPArp2/3 pathway. J Biol Chem. 2001 Jul 13;276(28):26448-52.
Ho HY*, Rohatgi R*, Ma L, Kirschner MW. (2001) CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family. Proc Natl Acad Sci USA. Sep 25;98(20):11306-11. *Equal contributions.
Rohatgi R*, Ho HY*, Kirschner MW. (2000) Mechanism of N-WASP activation by CDC42 and phosphatidylinositol 4,5-bisphosphate. J Cell Biol. Sep 18;150(6);1299-310. *Equal contributions.