“You make hyaluronan in abundant quantities at the sites of injuries,” Bollyky explains. “If you’ve ever twisted your ankle or gotten a bad burn, all that swelling and edema is basically caused by hyaluronan.” The molecule, he’s found, recruits both water and immune molecules to injuries. And blocking hyaluronan, his research team recently reported in the Journal of Clinical Investigation, can control chronic inflammation—the kind that’s not benefitting the body at all.

It’s a natural—and usually beneficial—response of the human body to react to a wound or pathogens with angry, red swelling. A sore knee or stomach, while an annoyance for anyone, is a sign that the immune system is sending all its molecular soldiers to defend and repair an injury. But, around the world, there are times the immune system falters, letting infectious diseases take their toll on populations. Likewise, there are times the immune system becomes a belligerent, over-responsive army—lashing out at the body it’s meant to defend when there’s nothing to attack. In both cases, clinicians have struggled to develop ways to treat these conditions; the immune system is complex and has many unknowns.

Now, a new generation of researchers, including fresh faces in Stanford’s Division of Infectious Diseases, are coming at the immune system, as well as invading pathogens, with new energy and new approaches. Their research has implications for conditions as common as diabetes and as globally far-reaching as tuberculosis.

In 2013, Paul Bollyky, MD (assistant professor, Infectious Diseases), launched his lab at Stanford to understand how the body responds to wounds and infections. He homed in on a molecule called hyaluronan, found in the nooks and crannies between cells, as being vital to mediating immune responses.

“You make hyaluronan in abundant quantities at the sites of injuries,” Bollyky explains. “If you’ve ever twisted your ankle or gotten a bad burn, all that swelling and edema is basically caused by hyaluronan.” The molecule, he’s found, recruits both water and immune molecules to injuries. And blocking hyaluronan, his research team recently reported in the Journal of Clinical Investigation, can control chronic inflammation—the kind that’s not benefitting the body at all.

Bollyky’s basic findings have the potential to treat autoimmune diseases like multiple sclerosis, characterized by inflammation of the nervous system. And they also may revolutionize the prevention of something far more common: type 1 diabetes. In patients with this autoimmune disease, inflammation of the pancreas is an early precursor to more severe symptoms. Blocking the hyaluronan, and therefore the inflammation, Bollyky thinks, could slow the progression of the disease.

But while treating inflammation is one lofty goal, diagnosing infectious diseases can be just as tricky. Jason Andrews, MD (assistant professor, Infectious Diseases), is tackling this challenge. He’s developing and evaluating low-cost diagnostic tools that can be used in settings like rural Nepal where electricity, water, and high-tech laboratories are hard to come by. These include an electricity-free, culture-based incubation and identification system for typhoid and an easy-to-use molecular diagnostic tool that does not require electricity. With his technology in development, Andrews is continuing epidemiologic research on diseases like tuberculosis to get a better handle on how they spread and what weak spots in their transmission cycles might lend themselves to intervention.

Bollyky’s basic findings have the potential to treat autoimmune diseases like multiple sclerosis, characterized by inflammation of the nervous system. And they also may revolutionize the prevention of something far more common: type 1 diabetes. In patients with this autoimmune disease, inflammation of the pancreas is an early precursor to more severe symptoms. Blocking the hyaluronan, and therefore the inflammation, Bollyky thinks, could slow the progression of the disease.

But while treating inflammation is one lofty goal, diagnosing infectious diseases can be just as tricky. Jason Andrews, MD (assistant professor, Infectious Diseases), is tackling this challenge. He’s developing and evaluating low-cost diagnostic tools that can be used in settings like rural Nepal where electricity, water, and high-tech laboratories are hard to come by. These include an electricity-free, culture-based incubation and identification system for typhoid and an easy-to-use molecular diagnostic tool that does not require electricity. With his technology in development, Andrews is continuing epidemiologic research on diseases like tuberculosis to get a better handle on how they spread and what weak spots in their transmission cycles might lend themselves to intervention.

The economic impact caused by the parasite of the trypanosome vector is estimated to be as much as $4 billion a year. The Food and Agricultural Organization estimates 37 African countries are affected by the tsetse fly and that its trypanosomosis kills around 3 million livestock per year.

The World Health Organization reports that the sleeping sickness delivered by the tsetse bite in humans is hard to diagnose and treat. Some 60 million people were once at risk with an estimated 300,000 new cases each year.

Sleeping sickness causes headaches, fatigue and weight loss; confusion and personality disorders occur as the illness progresses. If left untreated, people typically die after several years of infection.

Stanford Assistant Professor of Medicine Marcella Alsan had always wondered why the mineral-rich African continent—with so many natural resources, diverse climates, and arable land—remains so poor.

She launched into extensive research while working on her PhD in economics and has now come up with an intriguing theory: A pesky parasite prevented many precolonial Africans from adopting progressive agricultural methods, a phenomenon that still impacts parts of the continent today.

The tsetse fly has plagued Africa for centuries—having sent millions of people into the confusing stupor of sleeping sickness, while killing the cows and other livestock needed to plow their fields and feed their families.

Alsan writes in a paper published in The American Economic Review that the tsetse fly, which today is found only in Africa, drove precolonial Africans to use slaves instead of domesticated animals for agriculture. This limited their crop yields and the ability to transport goods.

“Communicable disease has often been explored as a cause of Africa’s underdevelopment,” writes Alsan, who is the only infectious-disease trained economist in the United States and a core faculty member of the Center for Health Policy/Center for Primary Care and Outcomes Research.

“Although the literature has investigated the role of human pathogens on economic performance, it is largely silent on the impact of veterinary disease,” she notes. “This is peculiar, given the role that livestock played in agriculture and as a form of transport throughout history.”

The economic impact caused by the parasite of the trypanosome vector is estimated to be as much as $4 billion a year. The Food and Agricultural Organization estimates 37 African countries are affected by the tsetse fly and that its trypanosomosis kills around 3 million livestock per year.

The World Health Organization reports that the sleeping sickness delivered by the tsetse bite in humans is hard to diagnose and treat. Some 60 million people were once at risk with an estimated 300,000 new cases each year.

Sleeping sickness causes headaches, fatigue and weight loss; confusion and personality disorders occur as the illness progresses. If left untreated, people typically die after several years of infection.

Fortunately, sustained control efforts have reduced the number of new cases, dropping below 10,000 annual cases for the first time in 50 years in 2009. This is in part due to an eradication effort using radiation sterilization techniques adopted by the International Atomic Energy Agency.

But the lingering economic impact from the tsetse has been monumental.

For her research, Alsan used geospatial-mapping software to mine data gathered by missionaries and anthropologists in the 1800s. She found that farming methods used in other developing regions of the world—such as the agricultural revolution in England—were not widely adopted in Africa.

“They pulled plows and carried carts. Their manure was used for fertilizer,” Alsan said. “They helped transport people and goods across land.”

She found that ethnic groups inhabiting tsetse-prone African regions were less likely to use domesticated animals to plow their fields, turning instead to the slash-and-burn technique still used in many parts of the continent today.

“These correlations are not found in the tropics outside of Africa, where the fly does not exist,” she writes. “The evidence suggests current economic performance is affected by the tsetse through the channel of precolonial political centralization.”

The FAO estimates that the tsetse fly infects nearly 10 million square kilometers in sub-Saharan Africa. Much of this large area is fertile but left uncultivated, a so-called green desert not used by humans and cattle. Most of the tsetse-infected countries are poor, debt-ridden, and underdeveloped.

And this is what triggered Alsan’s interest in the tsetse fly: How its deadly bite has altered the socioeconomic impact of a continent.

“It’s incredibly important to shine light on issues that are Africa-specific and therefore may not garner as much attention as those economic and medical issues that affect wealthier regions of the world,” she said.

Fortunately, sustained control efforts have reduced the number of new cases, dropping below 10,000 annual cases for the first time in 50 years in 2009. This is in part due to an eradication effort using radiation sterilization techniques adopted by the International Atomic Energy Agency.

But the lingering economic impact from the tsetse has been monumental.

For her research, Alsan used geospatial-mapping software to mine data gathered by missionaries and anthropologists in the 1800s. She found that farming methods used in other developing regions of the world—such as the agricultural revolution in England—were not widely adopted in Africa.

“They pulled plows and carried carts. Their manure was used for fertilizer,” Alsan said. “They helped transport people and goods across land.”

She found that ethnic groups inhabiting tsetse-prone African regions were less likely to use domesticated animals to plow their fields, turning instead to the slash-and-burn technique still used in many parts of the continent today.

“These correlations are not found in the tropics outside of Africa, where the fly does not exist,” she writes. “The evidence suggests current economic performance is affected by the tsetse through the channel of precolonial political centralization.”

The FAO estimates that the tsetse fly infects nearly 10 million square kilometers in sub-Saharan Africa. Much of this large area is fertile but left uncultivated, a so-called green desert not used by humans and cattle. Most of the tsetse-infected countries are poor, debt-ridden, and underdeveloped.

And this is what triggered Alsan’s interest in the tsetse fly: How its deadly bite has altered the socioeconomic impact of a continent.

“It’s incredibly important to shine light on issues that are Africa-specific and therefore may not garner as much attention as those economic and medical issues that affect wealthier regions of the world,” she said.

But that’s not the same thing, Desai argues, as understanding each sequential event in lung formation. So, after a medical fellowship in pulmonology and then a post-doctoral research fellowship in the lab of Stanford biochemist Mark Krasnow, MD, PhD (professor, Biochemistry), Desai made it his goal to paint a new, more detailed, picture of how lungs develop.

Inside each tiny airsac of the lung, two types of cells help the body breathe air. Alveolar type 1 (AT1) cells lie flat on the surface of each airsac, enabling the exchange of carbon dioxide and oxygen. Chunkier alveolar type 2 (AT2) cells studding the walls and ceilings produce surfactant, a fluid that coats the airsacs and keeps them from collapsing.

From the outside, the lungs develop like the roots of a plant; branching airways expand and grow increasingly more intricate, until they’ve filled every space they can with ever smaller passageways to capture oxygen from a breath of air. But inside the cells that make up these airways, an even more amazing molecular dance is taking place, one that creates new lung cells—as an embryo develops and, later, in adult lungs. It’s only in the past few years that researchers have begun to understand the details of this story, thanks to an interdisciplinary team at Stanford. And what they’re finding may allow clinicians to learn how to repair lungs in patients with conditions like emphysema and pulmonary fibrosis, or even treat lung cancer.

“You can take intermittent snapshots of what a tissue looks like as it develops, but to really understand it, you want to know what’s happening at a molecular scale between those snapshots,” says Stanford pulmonologist Tushar Desai, MD, MPH (assistant professor, Pulmonary and Critical Care). “To reveal that molecular level of development, though, is very painstaking, time consuming, and hard to get people excited about.”

Most researchers, he said, have skipped from the visual snapshots of lung development to genetic experiments. By engineering mice to lack certain genes, and then studying the effect on the lungs, they can elucidate what genes and molecules are key to the process. But that’s not the same thing, Desai argues, as understanding each sequential event in lung formation. So, after a medical fellowship in pulmonology and then a post-doctoral research fellowship in the lab of Stanford biochemist Mark Krasnow, MD, PhD (professor, Biochemistry), Desai made it his goal to paint a new, more detailed, picture of how lungs develop.

Inside each tiny airsac of the lung, two types of cells help the body breathe air. Alveolar type 1 (AT1) cells lie flat on the surface of each airsac, enabling the exchange of carbon dioxide and oxygen. Chunkier alveolar type 2 (AT2) cells studding the walls and ceilings produce surfactant, a fluid that coats the airsacs and keeps them from collapsing.

Scientists had previously hypothesized that progenitor cells in the developing lungs acted as the precursors for AT2 cells, and that some AT2 cells could then form from AT1 cells. But when Desai, in collaboration with Krasnow, traced the origin of lung cells, he discovered that a single alveolar progenitor cell directly formed both cell types. In the lungs of adults, however, these precursor cells were nowhere to be found. Instead, some AT2 cells acted as stem cells—able to form both new AT2 and AT1 cells. The results were published last year in the journal Nature.

“One of the most surprising things was that rare AT2 cells seem to be bifunctional,” says Desai. “Not only are they acting as stem cells, but they’re also apparently still secreting surfactant and keeping the lung functional that way.”

Desai went on to capture the transcriptome—levels of genes being used by a cell—in precursor and newly forming AT1 and AT2 cells. By determining what genes are turned on and off during this dynamic process, he thinks he may be able to find the molecular switch that’s flipped to generate new AT1 and AT2 cells.

Answering that question, Desai says, will not only satisfy his quest for understanding lung development, but could lead to new therapeutics for lung diseases.

Scientists had previously hypothesized that progenitor cells in the developing lungs acted as the precursors for AT2 cells, and that some AT2 cells could then form from AT1 cells. But when Desai, in collaboration with Krasnow, traced the origin of lung cells, he discovered that a single alveolar progenitor cell directly formed both cell types. In the lungs of adults, however, these precursor cells were nowhere to be found. Instead, some AT2 cells acted as stem cells—able to form both new AT2 and AT1 cells. The results were published last year in the journal Nature.

“One of the most surprising things was that rare AT2 cells seem to be bifunctional,” says Desai. “Not only are they acting as stem cells, but they’re also apparently still secreting surfactant and keeping the lung functional that way.”

Desai went on to capture the transcriptome—levels of genes being used by a cell—in precursor and newly forming AT1 and AT2 cells. By determining what genes are turned on and off during this dynamic process, he thinks he may be able to find the molecular switch that’s flipped to generate new AT1 and AT2 cells.

Answering that question, Desai says, will not only satisfy his quest for understanding lung development, but could lead to new therapeutics for lung diseases.