Rubin Tuder, M.D.

Rubin Tuder, M.D. Director, University of Colorado at Denver School of Medicine, Denver, Colorado Zipcode Based Nano-Imaging of Hypertensive Pulmonary Arteries Administered by the NHLBI Division of Lung Diseases, Airway Biology and Disease Branch FY 2009 Recovery Act Funding: $500,000 Additional Funding: Zipcode Based Nano-Imaging of Hypertensive Pulmonary Arteries Administered by the NHLBI Division of Lung Diseases, Airway Biology and Disease Branch FY 2010 Recovery Act Funding: $499,999 More information about the grant Microbiome in Chronic Obstructive Pulmonary Disease Administered by the NHLBI Division of Lung Diseases, Airway Biology and Disease Branch FY 2009 Recovery Act Funding: $76,792 More information about the grant Microbiome in Chronic Obstructive Pulmonary Disease Administered by the NHLBI Division of Lung Diseases, Airway Biology and Disease Branch FY 2010 Recovery Act Funding: $76,542 More information about the grant Total funding: $1,153,333

A pathologist is a physician who examines samples of body tissues to diagnose disease or, in some cases, to solve crimes. Like many pathologists, Rubin M. Tuder, M.D., wears a few different hats. His clinical work involves reading slides of patient cell samples to help other doctors confirm diagnoses, but he also performs autopsies to determine how a person died.

Research Focus: Dr. Tuder is also a researcher. His main interest is pulmonary hypertension, a serious but poorly understood breathing disorder that appears on its own or in people with other lung problems, like lung fibrosis (also called interstitial lung disease) or COPD (chronic obstructive pulmonary disease). Dr. Tuder's interest in studying pulmonary hypertension arose directly from the results of an autopsy he did on a patient who died from the condition 15 years ago. The case intrigued him and set him on a quest to find out more about this incurable disease that is usually diagnosed when it's too late to reverse its course.

Although many Americans are familiar with the term hypertension, or high blood pressure, few know much about pulmonary hypertension, which is high blood pressure that is confined to blood vessels in the lungs. In general, all-body hypertension is when the force of blood pushing against artery walls rises and stays high. Over time, this can damage various organs.

But pulmonary hypertension is different. In contrast, Dr. Tuder explained, circulation in the lungs is a "low-pressure" system, meaning that even after intense exercise in which the heart pumps much more blood than usual, blood pressure within the lungs remains low. Ironically, that's a bad thing, because the remarkable resilience of the lungs makes it vulnerable. More than 80 percent of a person's lungs' reserve must be gone before he or she experiences symptoms of pulmonary hypertension, such as shortness of breath. By that time, a lot of damage has been done, and medicines are only partially helpful.

Grant Close-Up: A major challenge to conquering pulmonary hypertension is that the only accurate way to diagnose pulmonary hypertension involves threading a catheter through blood vessels, an invasive procedure that requires hospitalization. What if doctors could find pulmonary hypertension much earlier, when treatment can have some impact?

Dr. Tuder's Recovery Act grant will take the first steps toward finding a way to do this. His previous research has suggested that abnormal cell growth - like what causes cancer - may explain why lung circulation becomes impaired in pulmonary hypertension. He and an expert team of biologists, chemists, engineers, and clinicians will use nanotechnology tools to look for cell-surface markers that signify the earliest signs of pulmonary hypertension.

Nanomaterials, like the ones Dr. Tuder and his team are developing, are very small - hundreds of times smaller than a single cell. He hopes that his teeny search-and-find devices will ultimately serve two purposes: detecting disease early and then targeting sick cells very precisely with new types of medicines.

Dr. Tuder's ultimate goal is to develop a nano-sized device-guided computerized tomography (CT) scanning method. This approach would be a big improvement over the surgery-based diagnosis that is done today. After two years of funding, Dr. Tuder expects to have a prototype imaging system that can scan a living rat with a disease similar to that in people with pulmonary hypertension.

"The biggest challenge in pulmonary hypertension is earlier diagnosis," Dr. Tuder said. "If patients can take medicines sooner, they will have a much better quality of life."

Economic Impact: This project enabled Dr. Tuder and his coworkers in Texas and Ohio to hire or retain several researchers. Dr. Tuder said that he thought the grant would have had a tough time getting funded through the typical application process, because it involves a fair amount of risk. But he asserted that the risk is matched with a high potential payoff.

Morbid Curiosity? Dr. Tuder is passionate about autopsies, which are a standard part of most pathologists' routine duties. A trained eye can unearth secrets about health and disease in real patients, Dr. Tuder said, explaining that the results usually tell a fascinating story if you know what clues to look for and how to interpret them.

He especially enjoys sharing his skills and problem-solving mindset with young doctors in training, as he coaches them in finding medical secrets hiding in autopsy results.

"It gives us a better grip on reality," he said.

By Alison Davis, Ph.D.

Last Updated:August 10, 2010