Lang Professor of Medicine
Professor of Developmental Biology
Dwight A. Towler is the Ira M. Lang Professor of Medicine, Barnes-Jewish Hospital at Washington University Medical Center. He received his MD-PhD degrees from Washington University, and completed his medical residency and metabolism fellowship at Barnes-Jewish Hospital. In addition to his academic career, Dr. Towler spent 4 years in industry – most recently as Senior Director of Bone Biology and Osteoporosis Research at Merck – and is co-inventor of novel, patented selective androgen receptor modulators with potential clinical applications in treatment of musculoskeletal frailty. Towler’s current research emphasizes transcription factor biology and vascular endocrinology relevant to bone formation and arterial calcification, supported by independent grants from the National Institutes of Health. Clinically, he specializes in bone and mineral diseases. His work has been recognized by the Charles E. Culpeper Foundation (1996), the American Society for Bone and Mineral Research (Fuller Albright Award 2000), and the American Society for Clinical Investigation (elected in 2004). In 2009, he was an invited faculty participant in the National Heart Lung and Blood Working Group on Calcific Aortic Stenosis. He holds membership on the editorial boards of Arteriosclerosis Thrombosis and Vascular Biology, Endocrinology, Bone, the Journal of Bone and Mineral Research, and the Journal of Clinical Investigation. A former regular member of the NIH Skeletal Biology Development and Disease (SBDD) review group (2004-2008), he now contributes ad hoc to the SBDD and AICS/Atherosclerosis study sections.
Tremendous unmet needs exist in musculoskeletal medicine. Osteoporosis and osteoarthritis are recognized as common and clinically important, but other serious skeletal disorders also afflict our society. In the setting of type 2 diabetes mellitus (T2DM), lower-extremity musculoskeletal disease is prevalent, costly, and exceedingly difficult to manage, with fracture, arthropathy, ischemia, ulcer, infection, and amputation commonly confronting patients and clinicians. Aortofemoral medial artery calcification is a strong predictor of risk for lower extremity amputation in patients with T2DM. While not occluding the lumen, mural elastinolysis and medial calcification compromise arterial elasticity — a material property necessary for Windkessel physiology that ensures normal tissue perfusion throughout the cardiac cycle. During aortic calcification, the Msx2-Wnt signaling cascade that controls orthotopic craniofacial bone formation is activated ectopically in the aortic valve and vessel wall. Diabetes and dyslipidemia induce expression of Msx2 in arterial myofibroblasts, upregulate aortic Wnt3a and Wnt7a gene expression, and activate pro-calcific canonical Wnt signaling in the valve and tunica media. By studying Msx2 actions, we have identified that paracrine Wnt/Dkk signals control arterial calcification and fibrosis in T2DM by regulating osteogenic lineage allocation of vascular mesenchymal progenitors. Inflammatory redox cues initiated by TNF-alpha and osteopontin modulate the sustained activation of this arterial injury response. We now study how strategies that differentially target skeletal vs. aortic Wnt signaling regulate bone formation, arterial calcification, and vascular fibrosis in murine models of diabetic arteriosclerosis.
Awards and Honors
2010: Selected by the National Institutes of Health’s Center for Scientific Review as a member of the Atherosclerosis and Inflammation of the Cardiovascular System (AICS) Study Section.