News & Research

Research Description

Because longstanding diabetes damages the body's blood vessels, organs throughout the body can begin to fail after 10-15 years. One of its most devastating complications is progressive and irreversible kidney injury, termed diabetic nephropathy (DN). While today's medications can slow the progression of DN, their benefits are incremental, not transformative. In fact, DN is so common and difficult to treat that it is the single most common reason patients in the US require chronic dialysis or need a kidney transplant.

The applicant's laboratory studies blood vessels.  They have compiled a substantial body of evidence suggesting that one protein within blood vessels, called Tie2, regulates a network of other proteins that, together, are critical to the normal healthy functions of blood vessels. Diabetes appears to inhibit Tie2, an effect that may initiate a cascade of events that culminates in DN and injury to other organs. The present application proposes to study the role of Tie2 in DN using a combination of rigorous approaches. If successful, the results of the proposed experiments will suggest Tie2 as a new therapeutic target in this disease, test the beneficial effects of a drug-like Tie2 activator, and even shed light on the root causes of other diabetic complications.

In short, the applicant's goal is to discover why diabetic blood vessels are diseased and, in turn, use that knowledge to develop entirely novel ways to prevent or reverse diabetes' most severe manifestations.

Research Profile

 What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?

Because longstanding diabetes damages the body's blood vessels, organs throughout the body can begin to fail after 10-15 years. One of its most devastating complications is progressive and irreversible kidney injury, termed diabetic nephropathy (DN). While today's medications can slow the progression of DN, their benefits are incremental, not transformative. In fact, DN is so common and difficult to treat that it is the single most common reason patients in the US require chronic dialysis or need a kidney transplant.

The applicant's laboratory studies blood vessels.  They have compiled a substantial body of evidence suggesting that one protein within blood vessels, called Tie2, regulates a network of other proteins that, together, are critical to the normal healthy functions of blood vessels. Diabetes appears to inhibit Tie2, an effect that may initiate a cascade of events that culminates in DN and injury to other organs. The present application proposes to study the role of Tie2 in DN using a combination of animal and cellular models of diabetes.

If successful, the results of the proposed experiments will suggest Tie2 as a new therapeutic target in this disease, test the beneficial effects of a drug-like Tie2 activator, and even shed light on the root causes of other diabetic complications. The applicant's goal is to discover why diabetic blood vessels are diseased and, in turn, use that knowledge to develop entirely novel ways to prevent or reverse diabetes' most severe manifestations.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond??

It is estimated that  30-40% of individuals with diabetes develop chronic kidney disease, a complication referred to as "diabetic nephropathy." Diabetic nephropathy can be devastating, culminating in a need for dialysis when the person's kidneys can no longer adequately clean the blood. Even more importantly, people with kidney complications of diabetes are at even higher risk of strokes, heart attacks, and heart failure than those whose for whom diabetes has not harmed the kidneys. In short, when the kidneys become damaged from longstanding diabetes, the patient's risk of dying escalates dramatically.  Our goal is to learn how diabetes injures the kidneys, and in turn, to use that knowledge to treat and prevent diabetic nephropathy.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?

Diabetes, particularly type 2, is no longer a disease confined to small pockets of affluent countries. It is a worldwide epidemic. Sadly, everyone I know knows someone who is suffering from diabetes. My father has glucose intolerance, my aunt is frankly diabetic, and I have several non-overweight friends and colleagues who have young families and have recently been diagnosed with diabetes. This disease reaches everyone, and I am no exception.

In what direction do you see the future of diabetes research going?

This worldwide killer deserves scientific attention on all fronts, ranging from public health measures to reduce childhood obesity to innovations in "closed-loop" technologies to give diabetics an artificial pancreas, to research into the reasons why a substantial fraction of diabetes sufferers develop complications involving the kidneys, eyes, and nerves. The history of scientific innovation has taught us, time and again, that breakthrough discoveries usually come from unexpected corners of the broader research community.  Diabetes research needs breakthroughs across the board--prevention, early treatment, and late treatment. The ADA has the right idea in supporting all of these endeavors.

Researchers will always bring the latest technologies to these questions--currently, those include personalized genetics, systems biology, miniaturization and multiplexing, nanoscale machines and drug delivery, and stem cells. While hard to predict which, if any, of these technologies will transform people's lives, I firmly believe that efforts of organizations like the ADA are enabling researchers to take enough "shots on goal" that we will have tangible breakthroughs in diabetes over the next 5-10 years. My laboratory is firmly committed to that vision ofdeploying science to improve lives.