We are interested in the role of repulsive guidance molecule (RGM) family members including RGMa, RGMb (Dragon) and RGMc (hemojuvelin) in various aspects of mammalian physiology and development.

Yin Xia, PhD 
Instructor of Medicine / Assistant in Biology 
185 Cambridge Street
Boston, MA 02114
Phone: (617) 724-9078
Fax: (617) 643-3182
Email: Xia.Yin@mgh.harvard.edu

 

We are interested in the role of repulsive guidance molecule (RGM) family members including RGMa, RGMb (Dragon) and RGMc (hemojuvelin) in various aspects of mammalian physiology and development. RGMs have been recently identified by us to be the first co-receptors for bone morphogenetic protein (BMP) signaling. The mechanisms by which RGMs regulate BMP signaling are being studied.

Hereditary hemochromatosis (HH) is a genetic disorder characterized by high levels of iron absorption from the diet, leding to iron overload. HH is linked to mutations in several genes, namely HFE, TFR2 (encoding transferrin receptor 2), HFE2 (encoding hemojuvelin/RGMc), or HAMP (encoding hepcidin). A small peptide secreted by the liver, hepcidin is an important regulator of body iron stores. Our studies have shown that hemojuvelin-mediated BMP signaling increases hepcidin expression both in-vitro and in-vivo. The precise combinations of BMP ligands and receptors used by hemojuvelin are being dissected using both in-vivo studies and in-vitro transfected liver cells.

RGMb (Dragon) is highly expressed in the ovary and kidney. Our Dragon knockout mice show defects in ovarian follicle development and kidney branching morphogenesis. The role of Dragon in ovarian function and in kidney development and function is being investigated.  

 

References:

  1. Xia Y, Sidis Y, Mukherjee A, Samad T, Brenner G, Woolf C, Lin HY, and Schneyer A. Localization and action of Dragon (RGMb), a novel BMP co-receptor, throughout the reproductive axis. Endocrinology. 2005. 146: 3614-3621.
  2. Xia Y, Yu P, Sidis Y, Schneyer A, Bloch KD, and Lin HY. Repulsive guidance molecule (RGMa) alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4. Journal of Biological Chemistry. 2007. 282: 18129-18140. 
  3. Xia Y, Babitt JL, and Lin HY. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood. 2008. 111: 5195-5204.
  4. Andriopoulos B Jr*, Corradini E*, Xia Y*, Faasse SA, Chen S, Grgurevic L, Knutson MD, Pietragelo A, Vukicevic S, Lin HY, and Babitt JL. BMP-6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nature Genetics. 2009. 41: 482-487. (*co-first author)