Lang Professor of Medicine
Professor of Molecular Biology and Pharmacology
Director, Bone and Mineral Diseases
| Office Location: | 514 Yalem Research Building | |
| Mailing Address: | 660 S. Euclid Ave. Campus Box 8301 St. Louis, MO 63110 |
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| Phone: | (314) 454-7434 | |
| Fax: | (314) 454-8434 | |
| E-mail Address: |
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Biography
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. Dr. 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). He holds membership on the editorial boards for the Journal of Bone and Mineral Research and Bone, and serves on the NIH Skeletal Biology Development and Disease study section.
Research Interests
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 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 differentially regulate bone formation and vascular calcification, respectively, using a murine model of diabetic vascular disease.
