My laboratory studies the role of the TGF-beta/BMP signaling pathways in health and disease.
Herbert Y. Lin, MD, PhD, FASN
Associate Professor of Medicine
185 Cambridge Street, CPZN-8216
Boston, MA 02114
Phone: (617) 726-5661
Fax: (617) 643-3182
Dr. Lin obtained his PhD from the Massachusetts Institute of Technology and Whitehead Institute in 1993. He also received his MD degree from Harvard Medical School in 1995 as part of the Harvard/MIT Division of Health Science and Technology program. He worked briefly as a post-doctoral research fellow at the Hubrecht Laboratory in the Netherlands. Dr. Lin then completed his medical Internship, Residency, and Clinical Fellowship in Nephrology at the Massachusetts General Hospital before joining the faculty of the Program in Membrane Biology and Nephrology Division in 1999. Now also a member of the MGH Center for Systems Biology, Dr. Lin has won numerous awards including the MGH Department of Medicine Stephen Krane Outstanding Young Investigator Award in 2008 and election to the American Society for Clinical Investigation in 2008. Dr. Lin is Board Certified in Internal Medicine and Nephrology by the American Board of Internal Medicine.
Dr. Lin's laboratory studies the role of the TGF-beta/BMP signaling pathways in health and disease. How TGF-beta/BMP ligands interact with receptors, and the role of the RGM/DRAGON family of novel BMP co-receptors in the regulation of iron metabolism are areas of active research. Ultimately, by studying this complex but important signaling system, he and his colleagues hope to shed light on diseases such as ischemic kidney disease, adult polycystic kidney disease, glomeruloscerosis, diabetic neuropathy, inflammatory bowel disease, hemochromatosis and anemia of chronic disease. His laboratory has recently published articles in prestigious journals including Nature Genetics, Nature Chemical Biology, Journal of Clinical Investigations, Blood, and the Journal of Biological Chemistry.
- Samad TA, Srinivasan A, Karchewsi LA, Jeong SJ, Campagna JA, Ji RR, Fabrizio DA, Zhang Y, Lin HY, Bell E, and Woolf CJ. DRAGON: a member of RGM-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neuroscience. 2004. 24(8): 2027-2036.
- Del Re E, Babitt JL, Pirani A, Schneyer AS, Lin HY. In the absence of the type III receptor, the TGF-beta type II receptor requires the type I receptor to bind TGF-beta2. J Biol Chem. 2004. 279(21): 22765-22772.
- Chuva de Sousa Lopes SM, Roelen BA, Monteiro RM, Emmens R, Lin HY, Li E, Lawson KA, and Mummery CL. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev. 2004. 18(15): 1838-49.
- Schneyer A, Sidis Y, Xia Y, Saito S, del Re E, Lin HY, and Keutmann H. Differential actions of follistatin and follistatin like 3. Mol Cell Endocrinol. 2004. 225(1-2): 25-8.
- Del Re E, Sidis Y, Fabrizio DA, Lin HY, Schneyer A. Reconstitution and analysis of soluble inhibin and activin receptor complexes in a cell-free system. J Biol Chem. 2004. 279(51): 53126-53135.
- Samad TA, Rebbapragada A, Bell E, Zhang Y, Sidis Y, Jeong SJ, Campagna JA, Perusini S, Fabrizio DA, Schneyer AL, Lin HY, Brivanlou AH, Attisano L, and Woolf CJ. DRAGON: a bone morphogenetic protein co-receptor. J Biol Chem. 2005. 280(14): 14122 - 14129.
- Bouley R, Lin HY, Raychowdhury MK, Marshansky V, Brown D, Ausiello DA. Down regulation of vasopressin type 2 receptor (V2R) after vasopressin-induced internalization: involvement of a lysosomal degradation pathway. Am J Physiol Cell Physiol. 288(6): C1390-401.
- Xia Y, Sidis Y, Mukherjee A, Samad T, Brenner G, Woolf C, Lin HY, and Schneyer AL. Localization and action of Dragon (RGMb), a novel BMP co-receptor, throughout the reproductive axis. Endocrinology. 2005. 146(8): 3614-21.
- Babitt JL, Zhang Y, Samad TA, Xia Y, Tang J, Campagna JA, Schneyer AL, Woolf CJ, and Lin HY. Repulsive Guidance Molecule (RGMa), a DRAGON Homologue, is a bone morphogenetic protein co-receptor. J Biol Chem. 280(33): 29820-29827.
- Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, Campagna JA, Chung RT, Schneyer AL, Woolf CJ, Andrews NC, and Lin HY. Bone morphogenetic protein signaling by hemojuvelin regulates hepicidin expression. Nat Genet. 2006 May. 38(5): 531-539.
- Gutierrez OM, Lin HY. Refractory hyponatremia. Kidney Int. 2007 Jan;71(1):79-82.
- Russo LM, del Re E, Brown D, Lin HY. Evidence for a role of TGF-β1 in the induction of post-glomerular albuminuria in diabetic nephropathy: amelioration by soluble TGF-β type II receptor. Diabetes. 2007 Feb. 56(2):380-8.
- Yi X, Bouley R, Lin HY, Bechoua S, Sun TX, Del Re E, Shioda T, Raychowdhury MK, Lu HA, Abou-Samra AB, Brown D, Ausiello DA. Alix (AIP1) is a vasopressin receptor (V2R)-interacting protein that increases lysosomal degradation of the V2R. Am J Physiol Renal Physiol. 2007 May. 292(5):F1303-13.
- Xia Y, Yu PB, Sidis Y, Beppu H, Bloch KD, Schneyer AL, Lin HY. Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4. J Biol Chem. 2007 Jun 22. 282(25):18129-40.
- Babitt JL, Huang FW, Sidis Y, Xia Y, Andrews NC, Lin HY. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J. Clin. Invest. 2007. 117(7):1933-1939.
- Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, Lin HY, Bloch KD, Peterson RT. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 2008 Jan. 4(1):33-41.
- Xia Y, Babitt JL, Sidis Y, Chung RT, Lin HY. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood. 2008 May 15. 111(10):5195-204.
- Zalyapin EA, Bouley R, Hasler U, Vilardaga JP, Lin HY, Brown D, Ausiello DA. Effects of the renal medullary pH and ionic environment on vasopressin binding and signaling. Kidney Int. 2008 Dec. 74(12):1557-67.
- Russo LM, Brown D, Lin HY. The soluble transforming growth factor-beta receptor: advantages and applications. Int J Biochem Cell Biol. 2009 Mar. 41(3):472-6.
- Andriopoulos B, Corradini E, Xia Y, Faasse S, Chen S, Grgurevic L, Knutson MD, Pietrangelo A, Vukicevic S, Lin HY, Babitt JL. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nature Genetics. 2009 Apr. 41(4):482-7.
- Corradini E, Garuti C, Montosi G, Ventura P, Andriopoulos B, Lin HY, Pietrangelo A, Babitt JL. Bone morphogenetic protein signaling is impaired in an Hfe knock-out mouse model. Gastroenterology. 2009. In Press.
- Wang L, Harrington L, Trebicka1 E, Shi HN, Kagan J, Hong CC, Lin HY, Babitt JL, Cherayil BJ. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis. J Clinical Investigation. 2009. In Press.
Active Laboratory Funding Sources:
- NIH/NIDDK RO1 DK069533-01. Principal Investigator: Lin. 2005 - 2010. Regulation of the BMP Signaling in the Kidney. (The aims of this grant are to study BMP signaling and BMP co-receptors during ischemic renal injury.)
- NIH/NIDDK RO1 DK071837-01. Principal Investigator: Lin. 2005 - 2010. Mechanisms of Action of Hemojuvelin. (The major goals are to study the mechanism and action of hemojuvelin as a novel BMP co-receptor in hemochromatosis.)