Volkhard Lindner, MD, PhD

Volkhard Lindner, MD, PhD 2017-08-08T12:00:15+00:00

Volkhard Lindner, MD, PhD

Faculty Scientist III

EDUCATION

MD, PhD: University of Tübingen
Postdoctoral Training: University of Washington, Seattle

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Functions

The focus of our laboratory is on understanding the function of the gene Collagen Triple Helix Repeat Containing-1 (Cthrc1), which was discovered in our laboratory as a gene expressed in tissues undergoing remodeling.

Lindner Fig 1Figure 1. Cthrc1 is highly induced in the outer layer (adventitia) of arteries in response to injury. This layer undergoes a significant scarring process with abundant deposition of collagen, which leads to narrowing of the artery lumen.

With genetic gain-of function and loss-of-function mouse models for Cthrc1 we seek to determine the functions of this molecule. Recent discoveries by our laboratory revealed that Cthrc1 functions as a pituitary- and hypothalamus-derived hormone with substantial circulating levels detectable in some human subjects. Evidence from genetic mouse models indicates that Cthrc1 plays a role in regulating body composition and voluntary physical activity. Increased body fat observed in Cthrc1 null mice is the result of inhibition of adipocyte differentiation by Cthrc1. The effects of Cthrc1 are mediated by inhibition of PPAR signaling, a critical signaling pathway for fat cell differentiation. Based on our findings that some healthy human subjects have substantially elevated Cthrc1 blood levels, our laboratory is interested in investigating how Cthrc1 affects metabolism, physical activity, and athletic performance both in genetic mouse models as well as in human subjects.

Lindner_Fig2

Figure 2. Cthrc1 null mice reveal increased visceral fat (in pink) and subcutaneous fat (in gray) as determined by microCT.

Lindner_Fig3

Figure 3. Cthrc1 (in brown) is found in the pituitary gland the paraventricular nucleus of the hypothalamus with evidence of secretion into the circulation in the median eminence.

Furthermore, identification and characterization of a putative Cthrc1 receptor is a major effort in the laboratory.

Mayasah Al Hashimi

Research Assistant I
malhashimi@mmc.org

Jin_Yongri_T

Yong-Ri Jin, PhD

Staff Scientist I
jiny@mmc.org

Mangoba_Armie_TArmie Mangoba

Technology Manager
mangog@mmc.org

Wang_Q_TQiaozeng Wang

Research Associate II
wangq@mmc.org

Left to Right: Yong-Ri Jin, Armie Mangoba, Qiaozeng Wang, Volkhard Lindner

A complete list of publications can be found on My NCBI

Jin Y-R, Stohn JP, Wang Q, Nagano K, Baron R, Bouxsein ML, Rosen CJ, Adarichev VA, and Lindner V. Inhibition of osteoclast differentiation and collagen antibody-induced arthritis by CTHRC1. Bone 2017; 97:153-167.  Stohn JP, Wang Q, Siviski ME, Kennedy K, Jin Y-R, Kacer D, DeMambro V, Liaw L, Vary CP, Rosen CJ, Prudovsky I, Lindner V. Cthrc1 Controls Adipose Tissue Formation, Body Composition, and Physical Activity. Obesity 2015; 23:1633-1642.

Duarte CW, Stohn JP, Wang Q, Emery IF, Prueser A, Lindner V. 2014. Elevated plasma levels of the pituitary hormone cthrc1 in individuals with red hair but not in patients with solid tumors. PLoS One 9: e100449.

Marks PC, Preda M, Henderson T, Liaw L, Lindner V, Friesel RE, Pinz IM. 2013. Interactive 3D analysis of blood vessel trees and collateral vessel volumes in magnetic resonance angiograms in the mouse ischemic hindlimb model. Open Med Imaging 7: 19-27.

Boucher JM, Harrington A, Rostama B, Lindner V, Liaw L. 2013. A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through p27kip1. Circ Res. 113: 975-985.

Liu G, Sengupta PK, Jamal B, Yang HY, Bouchie MP, Lindner V, Varelas X, Kukuruzinska MA. 2013. N-glycosylation induces the CTHRC1 protein and drives oral cancer cell migration. J Biol Chem. 288: 20217-20227.

Young K, Conley B, Romero D, Tweedie E, O’Neill C, Pinz I, Brogan L, Lindner V, Liaw L, Vary CP. 2012. BMP9 regulates endoglin-dependent chemokine responses in endothelial cells. Blood 120: 4263-4273.

Stohn JP, Perreault NG, Wang Q, Liaw L, Lindner V. 2012. Cthrc1, a novel circulating hormone regulating metabolism. PLoS One 7: e47142.

Apra C, Richard L, Coulpier F, Blugeon C, Gilardi-Hebenstreit P, Vallat JM, Lindner V, Charnay P, Decker L. 2012. Cthrc1 is a negative regulator of myelination in Schwann cells. Glia 60: 393-403.

Larman BW, Karolak MJ, Lindner V, Oxburgh L. 2012. Distinct bone morphogenetic proteins activate indistinguishable transcriptional responses in nephron epithelia including Notch target genes. Cell Signal 24: 257-264.

Cuttler AS, LeClair RJ, Stohn JP, Wang Q, Sorenson CM, Liaw L, Lindner V. 2011. Characterization of Pdgfrb-Cre transgenic mice reveals reduction of ROSA26 reporter activity in remodeling arteries. Genesis 49: 673-680.

McCulloch DR, Nelson CM, Dixon LJ, Silver DL, Wylie JD, Lindner V, Sasaki T, Cooley MA, Argraves WS, Apte SS. 2009. ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev Cell 17: 687-698.

Study Sections

  • National Institutes of Health, Vascular Cell and Molecular Biology (VCMB) Study Section, charter member

Editorial Boards

  • Member, Editorial Board Arteriosclerosis, Thrombosis and Vascular Biology
  • Member, Editorial Board International Angiology

Teaching Responsibilities

  • Member of the Graduate Faculty, University of Maine, Orono, ME
  • Member Cell, Molecular and Developmental Biology Program, Tufts Sackler School of Graduate Biomedical Sciences