Directory

The human genome is littered with small open reading frames (sORFs) encoding very small endogenous peptides, ranging from 20-100 amino acids. These are nestled within non-coding RNAs, pseudogenes and untranslated regions of conventional protein-coding genes and even introns. Such peptides, whose functions are just beginning to be understood, can act as extracellular signaling molecules (such as hormones and cytokines), antimicrobial agents, antigens, or regulatory moieties of larger proteins. Using a combination of bioinformatics, proteomics and next-generation sequencing, we are systematically defining these endogenous peptides and uncovering their functions, focusing on the cardiovascular system, which is well known for employing peptide hormones to effect homeostatic control (e.g. ANPs, Angiotensin, Apelin etc). We are also interested in the functional and structural relationships between RNAs and their resident sORFs, with the hypothesis that sORF-containing RNAs toggle between coding and non-coding states. sORF translation therefore modulates (non-coding) RNA activity, and vice versa. We are interested in elucidating the mechanisms underlying such toggling.

https://www.ho-lab.org/

Publications (with pubmed/journal links)

1.  ELABELA Deficiency Promotes Preeclampsia and Cardiovascular Malformations in Mice. Ho L*, Dijk VM, Tan SJC, Messerschmidt DM, Chng SC, Ong S, Ling KY,  Boussata S,  Goh GHY, Afink GB, Lim CY, Dunn NR, Solter D, Knowles BK, Reversade B* . Science. 2017 (in press) *Corresponding authors

2. ELABELA - APJ axis protects from pressure overload heart failure and Angiotensin II-induced cardiac damage. Sato T, Sato C, Kadowaki A, Watanabe H, Ho L, Ishida J, Yamaguchi T, Kimura A, Fukamizu A, Penninger JM, Reversade B, Ito H, Imai Y, Kuba K. Cardiovasc Res. 2017 Mar 23. (Medline)

3. The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development. Deshwar AR, Chng SC, Ho L, Reversade B, Scott IC. Elife. 2016 Apr 14;5. (Medline)

4. ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway. Ho L*, Tan SY, Wee S, Wu Y, Tan SJ, Ramakrishna NB, Chng SC, Nama S, Szczerbinska I, Chan YS, Avery S, Tsuneyoshi N, Ng HH, Gunaratne J, Dunn NR, Reversade B*. Cell Stem Cell. 2015 Oct 1;17(4):435-47. (Medline) *corresponding authors

5. ELABELA: a hormone essential for heart development signals via the apelin receptor. Chng SC*, Ho L*, Tian J, Reversade B. Dev Cell. 2013 Dec 23;27(6):672-80. (Medline) *first authors

6. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Kadoch C, Hargreaves DC, Hodges C, Elias L, Ho L, Ranish J, Crabtree GR. Nat Genet. 2013 Jun;45(6):592-601.(Medline)

7. esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function. Ho L, Miller EL, Ronan JL, Ho WQ, Jothi R, Crabtree GR. Nat Cell Biol. 2011 Jul 24;13(8):903-13. (Medline)

8. Chromatin remodelling during development. Ho L, Crabtree GR. Nature. 2010 Jan 28;463(7280):474-84. (Medline)

9. An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Ho L, Ronan JL, Wu J, Staahl BT, Chen L, Kuo A, Lessard J, Nesvizhskii AI, Ranish J, Crabtree GR. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5181-6. (Medline)

10. An embryonic stem cell chromatin remodeling complex, esBAF, is an essential component of the core pluripotency transcriptional network. Ho L, Jothi R, Ronan JL, Cui K, Zhao K, Crabtree GR. Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5187-91. (Medline)