Skip to main content

Fibrosis and Wound Healing

Photo of Howard Levinson, MD

Howard Levinson, MD

Office: Duke University Medical Center 316M, Green Zone Duke Clinic Durham, NC 27710
Phone: 919-684-8661

Scientific Focus

This laboratory investigates the mechanisms of fibrosis and tissue remodeling and aims to develop a novel small molecule inhibitor to prevent fibrocontractile disease progression. Approximately 80 million people worldwide are adversely affected by scar contracture. Yet, current treatments are largely unsuccessful, and preventive agents do not exist. There is a large unmet need for an effective pharmaceutical to prevent fibrosis. Fibrocontractile disease is ubiquitous throughout the human body. Scar contracture is putatively caused by fibroblast and myofibroblast contractility during the remodeling phase of repair.

Current hypotheses suggest that tractional force generation within these cells and subsequent scar contracture formation is primarily caused by myosin II activation and ensuing actin stress fiber formation, focal adhesion development, and cytoskeletal (microtubules and intermediate filaments) reorganization.However, it is unclear which myosins are activated in fibroblasts and myofibroblasts and how these myosins are regulated to increase tractional force generation and promote tissue remodeling. Filling this void is essential to the fulfillment of the long-term goal of developing a drug through small molecule high throughput screening, to prevent fibrocontractile disease.

The current hypothesis is that as fibroblasts become activated and transition into protomyofibroblasts and myofibroblasts, non muscle myosin II (NMMII) activation increases, either through upregulation of protein expression, through phosphorylation and activation of myosin regulatory light chain (MRLC), or through phosphorylation and inactivation of myosin phosphatase (MPYT), to enhance cellular tractional force generation and promote matrix remodeling.


Key Projects Underway

The main projects in the laboratory currently seek to:

  1. Evaluate the clinicopathologic correlation between expression of NMMII (isoforms IIA, IIB, IIC), myosin light chain kinase (MLCK), Rho kinase, MRLC, MYPT, and a-SMA, as they relate to scar contracture progression
  2. Clarify the relationship between NMMII regulation in fibroblasts, protomyofibroblasts, and myofibroblasts and tractional force generation

Approaches include:

  • In vitro techniques
  • Animal models of wound contraction and skin graft contraction
  • Investigation of human tissue

Contact Us

Howard Levinson

Latest Publications

Perez, J. E., M. A. Schmidt, A. Narvaez, L. K. Welsh, R. Diaz, M. Castro, K. Ansari, et al. “Evolving concepts in ventral hernia repair and physical therapy: prehabilitation, rehabilitation, and analogies to tendon reconstruction.” Hernia, September 21, 2020.

Full Text

Lin, Junquan, Ibrahim Mohamed, Po Hen Lin, Hitomi Shirahama, Ulla Milbreta, Je Lin Sieow, Yanfen Peng, et al. “Modulating Macrophage Phenotype by Sustained MicroRNA Delivery Improves Host-Implant Integration.” Adv Healthc Mater 9, no. 3 (February 2020): e1901257.

Full Text

VanDusen, Keith W., Sarada Eleswarpu, Eugene W. Moretti, Michael J. Devinney, Donna M. Crabtree, Daniel T. Laskowitz, Marty G. Woldorff, et al. “The MARBLE Study Protocol: Modulating ApoE Signaling to Reduce Brain Inflammation, DeLirium, and PostopErative Cognitive Dysfunction.” J Alzheimers Dis 75, no. 4 (2020): 1319–28.

Full Text

Ibrahim, Mohamad M., Jason L. Green, Jeffrey Everitt, David Ruppert, Richard Glisson, Frank Leopardi, Thomas Risoli, Maragatha Kuchibhatla, Randall Reynolds, and Howard Levinson. “Soft Tissue Anchoring Performance, Biomechanical Properties, and Tissue Reaction of a New Hernia Mesh Engineered to Address Hernia Occurrence and Recurrence.” J Med Device 13, no. 4 (December 1, 2019): 0450021–29.

Full Text