Stories about: Timothy Hla

Mitigating blood vessel damage from heart attack, stroke

Mouse hearts showing the impact of a therapeutic protein fusion on blood vessel health
Imaging of mouse hearts reveals widespread tissue damage (light-colored areas) after heart attack. At far right, however, mice that were treated with an engineered, optimized ApoM protein containing S1P have better tissue recovery than untreated mice (left) and mice that were given an inactive “dud” ApoM treatment (center). Credit: Hla lab/Boston Children’s Hospital

The average human has 60,000 miles of blood vessels coursing through their body. There are a number of mechanisms the body uses to keep that vast vascular network healthy, including a tiny fat molecule, a lipid called S1P, that plays a particularly important role.

S1P receptors dot the surface of the endothelium, a layer of cells that line the inside of all the body’s blood cells. Together, these so-called endothelial cells form a barrier between the body’s circulating blood and surrounding tissue. When S1P molecules activate their receptors, it suppresses endothelial inflammation and generally helps regulate cardiovascular health.

Now, researchers led by Timothy Hla, PhD, from the Boston Children’s Hospital Vascular Biology Program, report a novel therapeutic fusion that could trigger increased S1P receptor activity and recover blood vessel health following the onset of hypertension, atherosclerosis, stroke, heart attack and other cardiovascular diseases.

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A new inlet to treating neurological disease

Image of brains showing red tracer dye, indicating passage of molecules through the blood-brain barrier
These brain images tell a story about the blood-brain barrier: At left, the brain before injection of red tracer dye. At center, an injection of tracer dye shows only a small amount of molecules can infiltrate the blood brain barrier. At right, a new approach for crossing the blood-brain barrier increases the tracer’s penetration into brain tissue.

The blood-brain barrier was designed by nature to protect the brain and central nervous system (CNS) from toxins and other would-be invaders in the body’s circulating blood. Made up of tightly-packed cells, the barrier allows nutrients to pass into the CNS and waste products from the brain to be flushed out, while blocking entry of harmful substances.

A dysfunctional blood-brain barrier can contribute to CNS diseases including Alzheimer’s and multiple sclerosis (MS). But, ironically, the same blood-brain barrier can keep out drugs intended to treat CNS disease. Scientists have long been seeking ways to overcome this obstacle.

Now, Timothy Hla, PhD, and members of his laboratory in the Boston Children’s Hospital Vascular Biology Program have found a way to selectively control openings in the blood brain barrier to allow passage of small drug molecules.

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