Linda L. Demer M.D. Ph.D


Department of Bioengineering
Professor and Vice Chair, Department of Medicine
Professor, Department of Physiology
Director, UCLA Specialty Training and Advanced Research (STAR) Program

17-052 CHS



  • B.S., University of Arizona, 1977
  • M.D., The Johns Hopkins University School of Medicine, 1983
  • Ph.D., The Johns Hopkins University School of Medicine, 1983
  • Residency, Internal Medicine, Baylor College of Medicine, Texas Heart Institute, 1984-85
  • Fellowship, Cardiology, University of Texas School of Medicine, 1985-88

Awards and Recognitions

  • Elected Chair, Gordon Research Conference on Atherosclerosis, 2009
  • Fifth Annual Stewart-Niewiarowski Award for Women in Vascular Biology, 2007
  • Jeffrey M. Hoeg Award of the American Heart Association for Basic Science and Clinical Research, 2003
  • Franklin D. Murphy Research Prize, UCLA, 2002
  • UCLA Chancellor’s Award for Academic Border Crossing, 2002
  • Davidson Memorial Endowed Lectureship, Royal College of Physicians of Edinburgh, 2001
  • Stein/Oppenheimer Award for Biomedical Research, 1993

Research Interests

  • vascular biology
  • biomineralization
  • vascular calcification
  • mesenchymal stem cells

The research in my laboratory addresses the cellular and molecular mechanisms of artery wall mineralization, particularly atherosclerotic calcification.  We pioneered this field by showing that the process is regulated at the molecular level and occurs by osteoblastic differentiation of vascular stem cells stimulated by inflammatory cytokines, many of which are induced by oxidized lipoprotein nanoparticles.

To show the osteogenic mechanism of atherosclerotic calcification, we demonstrated expression of the potent osteoinductive factors, bone morphogenetic protein-2 and alkaline phosphatase, in human atherosclerotic plaque, and we developed an in vitro model of vascular cell calcification in which purified vascular cells spontaneously differentiate into osteoblastic cells and produce hydroxyapatite mineral, following the same cascade of osteogenic gene expression as skeletal osteoblasts.  We also elucidated the intracellular signal transduction pathways driving this process, including the cAMP/protein kinase A pathway and SMAD pathway, as well as the role of Runx2, the master regulator of osteoblastic differentiation.  In a serendipitous observation, we
found that oxidatively modified lipoproteins inhibit differentiation and mineralization of skeletal osteoblasts, offering a possible new mechanism for
age-related osteoporosis, and explaining the age-independent association of osteoporosis with hyperlipidemia.  As a result, wee have extended our
work into bone biology research, studying the effects of oxidized lipids and hyperlipidemia on bone formation and parathyroid hormone anabolism.

Based on a hunch,we demonstrated that the osteogenic vascular cells are also mesenchymal stem cells with multilineage potential. We further showed that these vascular stem cells self-organize in vitro into intricate, periodic patterns that are predicted by a mathematical model consisting of a system of partial
differential equations based on the principle of reaction-diffusion.  We identified the activator and inhibitor morphogens responsible for the reaction-diffusion phenomenon as bone morphogenetic protein (BMP-2) and its inhibitor, matrix GLA protein (MGP).   Predictions of the mathematical model were confirmed experimentally, including the ability of exogenous MGP to produce spot patterns and the ability of the MGP inhibitor, warfarin, to produce a doubling of stripe density.   These findings have major clinical implications given the widespread clinical use of calcium, vitamin D, warfarin, and parathyroid hormone.