Stories about: Judy Lieberman

“Teenage” red blood cells could hold the key to a malaria vaccine

A T cell (right) launches an attack on an immature red blood cell called a reticulocyte. This immune response could help design a malaria vaccine.
A T cell (right) launches an attack on an immature red blood cell (left) infected with a malaria parasite called P. vivax. At the arrow, the T cell breaches the infected cell’s membrane to deliver death-inducing enzymes. Credit: Lieberman lab/Boston Children’s Hospital

Malaria parasite infection, which affects our red blood cells, can be fatal. Currently, there are about 200 million malaria infections in the world each year and more than 400,000 people, mostly children, die of malaria each year.

Now, studying blood samples from patients treated for malaria at a clinical field station in Brazil’s Amazon jungle, a team of Brazilian and American researchers has made a surprising discovery that could open the door to a new vaccine.

“I noticed that white blood cells called killer T cells were activated in response to malaria parasite infection of immature red blood cells,” says Caroline Junqueira, PhD, a visiting scientist at Boston Children’s Hospital and Harvard Medical School (HMS).

For red blood cells, this activity is unusual.

“Infected red blood cells aren’t recognized by our immune system’s T cells in the same way that most other infected cells of the human body are,” says Judy Lieberman, MD, PhD, chair in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital.

Digging deeper, Junqueira, Lieberman and collaborators have found a completely unexpected immune response to malaria parasites that infect immature blood cells called reticulocytes. The revelation could help to design a new vaccine that might be capable of preventing malaria.

Their findings, published today in Nature Medicineuncover special cellular mechanisms and properties specific to “teenaged” reticulocytes and a strain of malaria called Plasmodium vivax that enable our T cells to recognize and destroy both the infected reticulocytes and the parasites inside them.

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News Note: A fresh perspective on RNA with big implications for drug development 

RNA-based drugs are the future of therapeuticsRibonucleic acid, or RNA, has long been underappreciated for its role in gene expression. Until recent years, RNA has been thought of merely as a messenger, shuttling DNA’s instructions to the genetic machinery that synthesizes proteins.

But new discoveries of RNA functions, modifications and its ability to transcribe sections of the genome that were previously considered “junk DNA” has led to the discovery of a huge number of new druggable targets.

These new insights into RNA’s complex purposes have largely been uncovered through ever-increasingly sensitive and affordable sequencing methods. As a result, RNA-based drugs now stand to greatly extend our ability to treat diseases beyond the scope of what’s possible with small molecules and biologics.

Although several RND-based drug approaches have already been established, some barriers still prevent these strategies from working broadly. In a review paper for Nature Structural and Molecular Biology, Judy Lieberman, MD, PhD, of the Program in Cellular and Molecular Medicine of Boston Children’s Hospital, lays out where RNA-based drug development currently stands.

Lieberman, who has helped pioneer the RNA-based drug revolution herself, was the first scientist to show in an animal disease model that small, double-stranded RNAs could be used as drugs and leveraged to knock down genes in cells.

Read Lieberman’s review: “Tapping the RNA world for therapeutics.”

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Microbial murder mystery solved

Bacteria, pictured in Petri dish culture here, can become resistant to antibiotics - but not killer cells. Why? New research from Boston Children's Hospital helps solve this microbial murder mystery.Immune cells called “killer cells” target bacteria invading the body’s cells, but how do they do this so effectively? Bacteria can quickly evolve resistance against antibiotics, yet it seems they have not so readily been able to evade killer cells. This has caused researchers to become interested in finding out the exact mechanism that killer cells use to destroy bacterial invaders.

Although one way that killer cells can trigger bacterial death is by inflicting oxidative damage, it has not yet been at all understood how killer cells destroy bacteria in environments without oxygen.

Now, for the first time, researchers have caught killer cells red-handed in the act of microbial murder

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When antibiotics fail: A potential new angle on severe bacterial infection and sepsis

bacterial infection sepsisBacterial infections that don’t respond to antibiotics are of rising concern. And so is sepsis — the immune system’s last-ditch, failed attack on infection that ends up being lethal itself. Sepsis is the largest killer of newborns and children worldwide and, in the U.S. alone, kills a quarter of a million people each year. Like antibiotic-resistant infections, it has no good treatment.

Reporting this week in Nature, scientists in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM) describe new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.

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Microptosis: Programmed death for microbes?

trypanosoma parasites immune defense apoptosis microptosis
Trypanosoma parasites in a blood smear. (CDC)

Of the various ways for a cell to die — necrosis, autophagy, etc. — apoptosis is probably the most orderly and contained. Also called programmed cell death (or, colloquially, “cellular suicide”), apoptosis is an effective way for diseased or damaged cells to remove themselves from a population before they can cause problems such as tumor formation.

“Apoptosis has special features,” says Judy Lieberman, MD, PhD, an investigator in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine. “It’s not inflammatory, and it activates death pathways within the cell itself.”

Conventional wisdom holds that apoptosis is exclusive to multicellular organisms. Lieberman disagrees. She thinks that microbial cells — such as those of bacteria and parasites — can die in apoptotic fashion as well. In a recent Nature Medicine paper, she and her team make the case for the existence of what they’ve dubbed “microptosis.” And they think it could be harnessed to treat parasitic and other infections.

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