Herzog, Dr. Walter

2021 Finalist: ASTech Awards

Dr. Walter HerzogDr. Walter Herzog’s research has revolutionized the understanding of muscle contraction and biomechanics.

The consequences of this work are only now being realized but will continue to shape research for decades.

In 2002, Dr. Herzog discovered that muscle contraction cannot be explained with the cross-bridge theory alone, and that a third structural protein contributes to muscle contraction. Based on his work, scientists for the past two decades attempted to identify this additional protein, unravel the molecular details of its function, and discover the potential implications for exercise, health physiology, and muscle mechanics.

Dr. Herzog made the fundamental discoveries that titin binds calcium and binds to actin when a muscle is activated, thereby regulating muscle contraction and active force. This discovery of titin’s function changed how scientists think about muscle contraction and force production. With the recent revelations of titin’s key role in many cardiac myopathies and skeletal muscle dystrophies, titin has become an intriguing target for the prevention of heart and skeletal muscle diseases. Dr. Herzog’s discovery that a structural protein in muscle contributes to muscle contraction and force fundamentally changed how textbooks of muscle physiology are written, and how curricula on muscle mechanics are taught.

There are two significant aspects to the findings.

The first is a fundamentally new understanding of a basic law of how nature works; in this particular case, how muscle contraction occurs on the molecular level. Second, titin is the biggest structural molecule ever discovered and it is abundant in muscle sarcomeres. Even though titin is encoded by a single gene, it has different isoforms for each muscle, specific to the functional needs of that muscle.  A knowledge of titin’s function in normal muscle is therefore of crucial importance to our understanding of how changes in titin isoform or concentration affect muscles and how such changes can be prevented or corrected in diseased heart and skeletal muscles.

The discoveries on the molecular mechanisms of cardiac and skeletal muscle contraction are of fundamental significance and have resulted in unprecedented recognition for Dr. Herzog globally. As often happens with fundamental discoveries, the full implications have only become apparent in recent years and continue to slowly emerge. Titin is the most abundant structural protein in the heart and in skeletal muscle, and changes in titin’s structure and concentration have been shown to be crucial determinants of many cardiac myopathies and skeletal muscle dystrophies. Therefore, the greatest impact of Dr. Herzog’s research and discoveries is in the medical field. Collaborating with leading children’s hospitals in the United States treating patients with spastic cerebral palsy are ongoing and supported, and models of muscular dystrophies are being studied with the aim to improve function of these diseased muscles. In 2019, Dr. Herzog was the Killam Prize Winner for engineering.

Dr. Herzog’s scientific and professional contributions are exceptional and enormous. He is a world class investigator with an internationally recognized research program … that is producing important results that are making a significant impact in the field and in people’s lives. Dr. Herzog has been very active in sharing his research knowledge with people of all ages from grade school students to older adults. He has been recognized with numerous awards. But his most important attribute is the fact that he is a very humble man. “

Kenton R. Kaufman, Ph.D., P.E
Director, Biomechanics/Motion Analysis Laboratory
Mayo Clinic