A Program with Heart (and Many Vessels)

The human vascular system is a complex network of blood vessels, some nearly an inch in diameter and others no wider than a single cell. Arteries, veins, and capillaries work in concert to transport blood, heal tissue, and deliver messages throughout the body. If lined up end to end, an adult human's blood vessels would stretch thousands of miles, but most people only notice their circulatory system when something goes wrong.

The Vascular Biology and Therapeutics (VBT) Program at Yale School of Medicine (YSM) was launched in 2000 to improve organ transplant outcomes and develop research projects based on observations made in the clinic. In the past 26 years, the program has grown and evolved with the population it serves, uniting 56 research laboratories under five core areas of study to address today’s most pressing concerns, including chronic inflammation and heart disease.

“I might be biased, but I think the vascular system is probably the most important organ to study,” says Carlos Fernandez-Hernando, PhD, Anthony N. Brady Professor of Comparative Medicine and director of the VBT Program at YSM. “Most people in western societies still die from some form of cardiovascular disease. As we age, the vascular system is the first to begin to decline, impacting the function of all other systems.”

The VBT Program launched with a distinct focus on transplant biology, reflecting not only a major health concern but also a passion of founder Jordan Pober, MD, PhD, Bayer Professor of Translational Medicine and professor of immunobiology at YSM. Pober studies how blood vessels help the immune system and how inflammation and immune responses affect blood vessel health.

Transplant science remains relevant today, and each director has expanded the program’s reach. In 2007, William C. Sessa, PhD, Alfred Gilman Professor Emeritus of Pharmacology, took the helm, giving the program its current name and expanding its scope to include therapeutics research.

When Fernandez-Hernando became director in 2022, he aimed to expand research into inflammation and the role of metabolism in cardiovascular disease. He has recruited many new investigators to help achieve this goal. The program’s current research objectives include understanding risk factors and disease onset, genetic contributions, vulnerabilities associated with aging, and developing new technology for studying the vasculature and treating patients.

Although researchers in the VBT Program are tackling a broad swath of issues, they share a common goal: learning to support healthy living. Part of what makes the program unique is that it brings together basic science researchers and physician-scientists, allowing information to move seamlessly from the lab to the clinic and back.

This was a key part of the program’s original mission and is still important today.

“A clinician can observe something in a human patient that needs to be studied at the basic science level before it can be understood and treated,” says Fernandez-Hernando. “Still, in many cases, the results of basic science research allow us to understand and characterize human disease. Discoveries are bidirectional.”

Infections, injuries, and chronic disease throw us out of balance. The body, namely the immune system, is forced to reallocate resources to provide more energy for healing. This might induce fatigue or general malaise, but it is a critical step in the road to recovery.

Sometimes, however, the process stalls and people don’t get better. Two people confronted with the same infection may have very different responses. For an elderly person, a broken bone may lead to faster decline while a teenager with a fracture is hardly hindered. The body has many tricks for restoring biological equilibrium, or homeostasis, but its ability to do so changes over time.

Stephania Libreros, PhD, studies the recovery process, looking at how inflammation follows injury, how it is resolved, and why it sometimes becomes chronic. The highly coordinated processes that resolve inflammation are set in motion by the first inflammatory responses.

“We experience inflammation from the moment we are born, and even before, as a fetus. Waves of inflammation follow new information, like an infection or vaccine, but then you get better. And as adults, we start to lose that,” says Libreros, an assistant professor of pathology at YSM.

Inflammation, although associated with ill-health, is a protective response. When the immune system recruits cells to fight infection or repair injured tissue, it causes inflammation. If too many cells respond, or respond for too long, that protective response can become detrimental and produce chronic inflammation.

“In my view, chronic inflammation reflects repeated breakdowns in the body’s resolution programs,” says Libreros. “When these programs fail, immune cells remain activated, inflammatory mediators persist, and tissues are exposed to ongoing damage. This is particularly important in the vasculature, where persistent inflammation can disrupt vessel function and contribute to disease across many organs.”

Her group studies the vascular system to understand why it sometimes fails, putting a person at risk instead of helping them heal.

One of the projects in her lab involves tracking how a specific class of immune cells, called neutrophils, move. Although neutrophils protect the body from infection, an excessive or dysregulated neutrophil response can damage tissue.

People with severe infections can develop sepsis, a life-threatening condition in which an imbalanced immune response begins to damage organs. Many people with sepsis have elevated neutrophil counts. As the disease progresses, these cells become dysfunctional and show signs of impaired movement, among other defects.

Tracking these changes might help doctors make more accurate prognoses and inspire researchers to look for therapeutics. If stalled cells can be reactivated, for example, it may help subdue the immune response before it causes irreparable damage.

Libreros’ lab is especially interested in understanding which natural healing signals might be missing in patients who do not recover from infection, and how losing those signals may prolong inflammation.

“We’re trying to figure out why some resolve, and some don’t,” says Libreros. “For me, that’s what it always comes down to.”

Fifteen years ago, the American Heart Association formally recognized preeclampsia, among other pregnancy complications, as a risk factor for cardiovascular disease. The telltale sign of preeclampsia is high blood pressure, starting after 20 weeks and sometimes persisting after pregnancy. Other clues include protein in the urine, indicating kidney dysfunction.

Preeclampsia is thought to stem from abnormal development of the placenta, but researchers are still working to uncover exactly what goes wrong and when. The condition increases risks for both mother and child during pregnancy and remains a leading cause of maternal mortality worldwide. Mothers with preeclampsia often require acute care during and immediately after pregnancy, but researchers only recently began to investigate the long-term effects.

Lauren Biwer, PhD, is one of those researchers. Biwer, an assistant professor in comparative medicine at YSM, studies female-specific mechanisms of cardiovascular disease. She has focused much of her career on studying blood pressure regulation and joined the VBT Program in 2023. The origins of her professional interest are personal; Biwer’s sister was diagnosed with preeclampsia during her pregnancy years ago.

“I realized we hardly knew anything about it,” Biwer says. “That opened the door for me to discover how little we knew, in general, about cardiovascular complications during pregnancy. Or even how a healthy pregnancy impacts cardiovascular health later in life.”

Part of the problem, Biwer notes, is that research subjects are often male. Concerns about the health of people who are or might become pregnant have led to the widespread exclusion of women from clinical research. Even mouse studies have prioritized male mice due to misconceptions that the estrous cycle—the female mouse’s reproductive cycle—could complicate results. Sex imbalances in research are improving, but the field is still making up for lost time.

“It’s hard to appreciate where we are now without addressing the previous limitations,” says Biwer. “So many aspects of the cardiovascular system differ depending on sex. If you don’t look, you’re just leaving those discoveries on the table.”

Her work zooms into the level of individual vessels. Biwer’s lab is known for “ex-vivo microvascular function,” or watching blood vessels work outside the body. They can remove arteries from the body and place them on an apparatus that mimics biological conditions to study how blood vessels respond to various stimuli.

One goal of this work is to understand how preeclampsia impacts the circulatory and immune systems, as well as organs like the kidney. Identifying which cells and molecules are involved and how they change over time could also reveal impactful drug targets.

Biwer hopes this foundational work will pave the way for safely testing potential therapeutics in women down the line. In the meantime, she’s also taken a personal interest in raising awareness.

“People don’t necessarily know that preeclampsia is linked with this future risk of cardiovascular disease,” says Biwer. “These complications are very common. If someone has this experience, they should follow up with a cardiologist.”

Benjamin Landis, MD, is relatively new to the VBT Program. He transferred to YSM from Indiana University in August 2025. As a pediatric cardiologist and physician-scientist at YSM, Landis studies the heart, specifically the aorta—the thick artery that wraps around the heart and runs down the spine. He has dedicated most of his career to treating children affected by a condition called aortic aneurysm, in which the artery wall threatens to fail.

Structural abnormalities in the heart and some genetic conditions such as Marfan syndrome weaken the aorta, which has the critical function of supplying oxygen-rich blood to the rest of the body. A weak aorta is more likely to tear, and a tear can lead to catastrophic blood loss and death.

Diagnosing an aortic aneurysm can be tricky. The condition, often asymptomatic, might not give any cause for concern until it creates an emergency. With his work, Landis hopes to improve the process by which aortic aneurysms are diagnosed and develop a system for classifying patients according to their individual risk.

“Aortic aneurysm is a condition that spans the lifetime,” says Landis, associate professor of pediatrics (cardiology). “My goal is to use precision medicine methods to individualize care, to tailor the treatment to a person’s risk, which is a real gap in how we take care of these patients.”

Many of his patients are diagnosed as children, which means they will face years of managing the condition, and treatment options are relatively limited. For serious cases, surgeons can remove and replace the weak portion of the aorta. If the threat is less acute, medications that lower blood pressure can help reduce strain on the artery wall.

Treatment can help prevent further weakening, and stave off tearing, but the risk of this occurring varies widely by case. Looking for patterns in patient DNA can help researchers assess a person’s risk by matching genes or gene variants with disease severity. This information, paired with a comprehensive physical assessment of the aorta through cardiac imaging, could help fill the patient care gap Landis has observed from working with kids and families.

“It’s really exciting to be in a place where there has already been so much focus and progress toward understanding the adult pathology of vascular disease,” he says. “I want to leverage the opportunity here in the Vascular Biology and Therapeutics Program to develop the technologies that are most advanced when it comes to genetic analyses of patient samples and advance knowledge that will allow us to do better as a field on the clinical side as well.”

Transporting oxygen throughout the body is one of the vascular system’s fundamental duties. Each breath we take draws air into the lungs, where it diffuses into the blood through tiny, capillary-rich sacs at the end of the airway. These sacs, called alveoli, have a specific structure that maximizes the amount of surface area for absorbing oxygen and expelling carbon dioxide.

Blood vessels in the lung, and everywhere in the body, are lined by long, slender endothelial cells. The endothelial cell membrane is picky about what is allowed to pass through. It can allow immune cells to move through the bloodstream during illness or injury, for example, and the structure of the cells can differ depending on location. In the brain, endothelial cells knit close together to provide additional protection to this extra-sensitive tissue.

Terren Niethamer, PhD, an assistant professor of comparative medicine at YSM, joined the VBT Program in October 2025 to study how endothelial cells work with other cells to keep the lungs working well.

“In the lungs, blood vessels form this beautiful three-dimensional structure to facilitate gas exchange. It’s really really awesome,” says Niethamer.

Niethamer is a developmental biologist by training. She grew interested in blood vessels while studying head and facial development as a doctoral student. After completing a postdoc at the University of Pennsylvania Perelman School of Medicine, Niethamer accepted an offer to start a lab at the National Cancer Institute.

As a probationary employee, she was among those let go early in 2025.

Now, at the VBT Program, Niethamer is diving back into her work. One of her current projects involves trying to understand what happens to endothelial cells in the lung after an infection. In a recent study, Niethamer and colleagues found that some endothelial cells undergo a transformation after infection by the flu virus. They activate a different set of genes and never go back to normal. The researchers aren’t sure whether this response is advantageous or harmful.

“I’m interested in studying how those gene expression changes translate to changes in function, and how that impacts the tissue as a whole,” says Niethamer.

This cellular response is not unique to the flu, either. Other lung injuries can trigger endothelial cells in the same way. Niethamer suspects that this could also occur in other tissues.

“It would be really interesting to collaborate with people in the VBT Program who are studying the liver, or bone marrow, to find out if they see the same patterns,” says Niethamer. “One of the big advantages of the program is that we have people studying the vasculature everywhere in the body to understand how it contributes to health and disease across the full spectrum.”