Donald E. Ingber

Last updated
Donald E. Ingber
Donald Ingber headshot.jpg
Ingber in 2010
Born1956 (1956)
Academic background
Education Yale College and Yale Graduate School of Arts and Sciences

Significant contributions

Ingber presenting at PopTech 2010 Donald Ingber 2010.jpg
Ingber presenting at PopTech 2010

Ingber is best known for his discovery of the role mechanical forces play in developmental control and in cancer formation, and for his application of these principles to develop bioinspired medical devices, nanotechnologies, and therapeutics. Ingber's early scientific work led to the discovery that tensegrity architecture [16] - first described by the architect Buckminster Fuller and the sculptor Kenneth Snelson - is a fundamental design principle that governs how living systems are structured, from individual molecules and cells to whole tissues, organs and organisms. [17]

Ingber's work on tensegrity led him to propose that mechanical forces play as important a role in biological control as chemicals and genes do, [18] and to investigate the molecular mechanism by which cells convert mechanical signals into changes in intracellular biochemistry and gene expression, a process known as "mechanotransduction." [19] Ingber determined that living cells use tensegrity architecture to stabilize their shape and cytoskeleton, that cellular integrins function as mechanosensors on the cell surface, and that cytoskeletal tension (or "prestress," which is central to the stability of tensegrity structures) is a fundamental regulator of many cellular responses to mechanical cues. [20] Ingber's tensegrity theory also led to the prediction in the early 1980s that changes in extracellular matrix structure and mechanics play a fundamental role in tissue and organ development, and that deregulation of this form of developmental control can promote cancer formation. [21]

Ingber's contributions in translational medicine include discovery of one of the first angiogenesis inhibitor compounds (TNP-470) [22] to enter clinical trials for cancer, creation of tissue engineering scaffolds that led to clinical products, development of a dialysis-like blood cleansing device for treatment of blood stream infections that is moving towards clinical testing, [23] [24] creation of a mechanically-activated nanotechnology for targeting clot-busting drugs to sites of vascular occlusion, [25] and co-development of a new surface coating based on Slippery Liquid Infused Porous Surfaces (SLIPS) for medical devices and implants that could eliminate the conventional dependency on anticoagulant drugs that pose life-threatening side-effect risks. [26]

One of his more recent innovations is the creation of tiny, complex, three-dimensional models of living human organs, known as "organs-on-chips" (Organ Chips), which mimic complicated human organ functions in vitro as a way to potentially replace traditional animal-based methods for testing of drugs and toxins. [27] The first human Organ Chip, a human Lung Chip, was reported in Science in 2010. [28] Created using microchip manufacturing methods[ citation needed ], the Lung Chip is a complex three-dimensional model of a breathing lung that incorporates living human lung alveolar epithelial cells interfaced with endothelial cells within microfluidic channels cast in silicone rubber, which recapitulate structure and function of the tissue-vasculature interface of lung alveolus (air sacs). In 2012, Ingber and his team demonstrated in a study in Science Translational Medicine the ability to mimic a complex human disease on the Lung Chip — specifically pulmonary edema, known commonly as “fluid on the lungs” — and to identify new therapeutics using this model. [29] As an alternative to animal studies, Organ Chips could be used to study the safety and efficacy of new drugs, accelerating the introduction of new drugs to market while significantly lowering research costs. [30] Ingber's group has since expanded this technology to develop other model organs, including the intestine, [31] kidney, [32] bone marrow, [33] blood-brain barrier, [34] and liver. In 2012, Ingber's team was awarded a DARPA contract to string together multiple Organ Chips to build an automated human body-on-chips that will recapitulate whole-body physiology. [35] This system could be used in combination with computational modeling to rapidly assess responses to new drug candidates, providing critical information on their safety, efficacy, and pharmacokinetics. [36]

Other new technologies from Ingber's lab include development of a fully biodegradable plastic alternative inspired by natural cuticle material found in shrimp shells and insect exoskeletons, known as “Shrilk”; [37] a mechanically activated nanotherapeutic that selectively directs clot-busting drugs to sites of vascular occlusion while minimizing unintended bleeding; [38] an siRNA nanoparticle therapy that prevents breast cancer progression; [39] a dialysis-like sepsis device that cleanses blood of all infectious pathogens, fungi and toxins without requiring prior identification; [40] a surface coating for medical materials and devices that prevents clot formation and bacteria accumulation that reduces the need for use of conventional anticoagulant drugs that frequently result in life-threatening side effects, [26] and a computational approach to diagnostics and therapeutics that incorporates both animation and molecular modeling software to virtually develop and test potential drugs designed to fit precisely into their targets’ molecular structures. [41]

Leadership and public service

Earlier in his career, Ingber helped to bridge Harvard University, its affiliated hospitals, and the Massachusetts Institute of Technology (MIT) through his involvement in the Center for Integration in Medicine and Innovative Technology, Harvard-MIT Division of Health Sciences and Technology, and Dana-Farber/Harvard Cancer Center[ citation needed ]. He also has been a member[ citation needed ] of the Center for Nanoscale Systems and the Materials Research Science and Engineering Center at Harvard, as well as the MIT Center for Bioengineering.

In 2009, Ingber was named Founding Director[ citation needed ] of the Wyss Institute for Biologically Inspired Engineering at Harvard University, which was launched with a $125 million gift— which at the time was the largest philanthropic gift in Harvard's history—from Swiss billionaire Hansjörg Wyss. The Wyss Institute was founded to enable high-risk research and disruptive innovation, and to catalyze the field of biologically inspired engineering in which newly uncovered biological design principles are leveraged to develop new engineering innovations in the form of bioinspired materials and devices for medicine, industry, and the environment. [42] The Institute is a partnership[ citation needed ] among Harvard University, its major affiliated hospitals (Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, Spaulding Rehabilitation Hospital), Boston University, Massachusetts Institute of Technology, Tufts University, University of Massachusetts Medical School, Charité - Universitätsmedizin Berlin, and University of Zurich.

Ingber is a member of the National Academy of Medicine, the National Academy of Inventors, the American Institute for Medical and Biological Engineering, and the American Academy of Arts and Sciences [ citation needed ]. He served as a member of the Space Studies Board [43] of the U.S. National Research Council (NRC), which advises the National Academy of Sciences, National Academy of Engineering, and National Institute of Medicine, and he chaired its Committee on Space Biology and Medicine. He has been an external reviewer of multiple NRC reports, including “Plan for the International Space Station,” “Future Biotechnology Research on the International Space Station,” [44] "Assessment of Directions in Microgravity and Physical Sciences Research at NASA", [45] and “The Astrophysical Context of Life.” [46]

Ingber also has served as a consultant[ citation needed ] to numerous companies in the pharmaceutical, biotechnology, and cosmetics industries, including Merck, Roche, Astrazeneca, Biogen, Chanel, and L’Oreal, among others. He currently chairs[ citation needed ] the Scientific Advisory Boards of Emulate, Inc. and Boa Biomedical, Inc.

He is an advisory board member for Integrative Biology . [47]

Awards

Ingber has received numerous awards and distinctions, including:

Ingber has also been named to multiple Who's Who lists for his diverse contributions including: Science and Engineering (1991), America (1994), the World (1997), Medicine and Healthcare (1999), Business Leaders and Professionals—Honors Edition (2007), and was honored with the Albert Nelson Marquis Lifetime Achievement Award in 2018. [67]

Art and design exhibitions

Ingber collaborates internationally with artists, architects, and designers, as well as scientists, physicians, engineers, and the public. Examples of his involvement in the art/design community include:

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