John W. Lawler, Ph.D, NHLBI and ARRA

If you can imagine what your healthcare is today, it would be exactly the same forever without basic research. It is basic research and biomedical research that gives us the advances to understand new approaches, new therapies and new drugs. My laboratory work is on the thrombospondins, which is a family of extracellular matrix proteins. If one thinks about a building being constructed, the iron I-beams might be like a collagen fibril within the skin or in other tissues, and the thrombospondins might be like the workers that come and assemble those collagen fibrils or those I-beams in a specific way, and then they are also important when the tissue needs to be repaired, so you might think that if there was an injury or damage to the building the workers would come and they would put up a scaffold, and the thrombospondins kind of function to help build that scaffold and help guide the tissue. We have been funded for the last 30 years by the National Institutes of Health, and we currently had a grant that was running for 15 years but those funds would not begin for quite sometime, and so I was delighted to learn that we would have the opportunity to have some support from the Recovery Act because it helped us to purchase equipment but also enabled me to retain a postdoctoral fellow whose funding had run out from another mechanism. When people talk about going from the bench to the bedside it is a very tedious, very complicated process that involves a lot of basic science. Thrombospondins are important for angiogenesis, this process where new blood vessels are generated from existing blood vessels, which is very important for tumor progression and metastasis. It is also then very important for the tissue remodeling after a heart attack, so that as you can imagine the collagen fibrils and the tissue has been injured as a result of a lack of blood supply, a recovery process begins that involves the recruitment of immune cells and other cells, and the thrombospondins seem to play an important role in this process, and the Recovery Act really gives us the opportunity to kind of push this project forward in multiple directions.

John W. Lawler, Ph.D.
Professor of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Thrombospondin 4 A1
Administered by the NHLBI Division of Intramural Research, Cell Biology and Physiology Center
FY 2009 Recovery Act Funding: $711,148

Space vs. Cells: Like many kids growing up in the 1950s, John (Jack) Lawler, PhD was glued to the black-and-white TV sets in school auditoriums that chronicled America's first human ventures into space. For Dr. Lawler, the pull of space was almost too much to ignore. In college, he seriously considered a career in astrophysics, but he later turned his attention to more earthly matters, wanting to achieve concrete results that could help advance human health.

"Astrophysics was interesting, but I wanted to do something more experimental and less theoretical," he said. "I became intrigued by biological processes and human physiology." Dr. Lawler went from pondering the structure of the universe to learning about how structures are built at the cellular level deep within the human body.

Protein Exploration: "We do very basic science," Dr. Lawler explained, "very early in the process." Dr. Lawler is most interested in teasing out the various mysteries of a family of proteins known as TSPs, or thrombospondins, which could provide pathways to helping in specific medical research areas, such as heart disease, arthritis, wound healing, and cancer. The work could lead to new insights into what causes arthritis and skeletal dysplasias, a family of disorders that hinder proper bone growth. A grant from the National Heart, Lung, and Blood Institute will help his lab focus on one particular TSP called cartilage oligomeric matrix protein (COMP).

When mutations appear in COMP, they can result in skeletal dysplasias, an effect the Lawler lab wants to study. Since the mutations occur in a region of COMP that is found in all of the TSPs, the knowledge gained will provide insight into the function of other TSPs in a wide range of normal and disease processes. In addition to the role of certain TSPs in bone development, some of the proteins play important roles in wound healing and new blood vessel growth, which can help with tissue repair. Other TSPs affect the immune response or the formation of synapses in the brain. Dr. Lawler's study is aimed at understanding how the TSPs direct the assembly of the scaffolding that leads to cartilage growth and repair. "It's been an exciting adventure," Lawler said of his 30-year exploration of the structure and function of the TSPs.

Brain Drain: As an established researcher, he has seen National Institutes of Health funding rise and fall over the years. During economic downturns, such as the current one, more competition for money can lead bright minds to exit the sciences. Young men and women who held promise for solving medical mysteries might move into patent law or other fields due to a lack of funding to establish research careers, Dr. Lawler says.

This Recovery Act grant will help Dr. Lawler keep his lab together. Part of the grant money will help him hold onto a post doctoral researcher, who may have had to leave the Lawler lab for a lack of funding. The Recovery Act funding also helped save the job of Dr. Lawler's 20-year lab manager, whom he refers to as the "heart and soul of the lab."

A voice from his earlier interest in astrophysics , famed astronomer Carl Sagan, provides a quote that inspires Dr. Lawler's own biological work. "Somewhere, something incredible is waiting to be known." Dr. Lawler hopes that learning about the many functions of TSPs will lead to important discoveries and new insights into new strategies to alleviate the suffering associated with arthritis, skeletal dysplasias, heart disease and cancer.