platelets
Tackling Cancer Metastasis with Engineered Blood Platelets
Posted on by Dr. Francis Collins
Credit: Dan Hixson/University of Utah College of Engineering, Salt Lake City
When cancer cells spread to new parts of the body in a process called metastasis, they often get there by traveling through the bloodstream. To avoid alerting the immune system and possibly triggering their demise, cancer cells coax circulating blood platelets to glom onto their surfaces and mask them from detection. This deceptive arrangement has raised a tantalizing possibility: What if blood platelets could be programmed to recognize and take out those metastasizing cancer cells?
Tara Deans, University of Utah, Salt Lake City, was recently awarded a 2019 NIH Director’s New Innovator Award to do exactly that. It’s an exciting opportunity for a researcher who stumbled onto this innovative strategy quite by accident.
Deans is a bioengineer and expert in designing synthetic gene circuits. These circuits consist of small collections of genetic “parts” that can be assembled and integrated to program cells to behave differently than their natural counterparts [1]. In her initial work, Deans got these specialized gene circuits to prompt blood-forming stem cells to mass-produce platelets in the lab.
But blood platelets are unusual cells. They’re packed with many proteins that help to repair small nicks in blood vessels and stop the bleeding when we’re injured. Blood platelets do so even though they lack a nucleus and DNA to encode and make any of the proteins. Their protein cargo is pre-packaged and comes strictly from the bone marrow cells, called megakaryocytes, that produce them.
Deans realized that engineering platelets might pose a rare opportunity. She could wire the needed circuitry into the blood-forming stem cells and engineer them to make any desired therapeutic proteins, which are then loaded into the blood platelets for their 8- to 10-day lifespan. She started out producing blood platelets that could safely carry functional replacement enzymes in people with certain rare metabolic disorders.
As this research progressed, Deans got some troubling personal news: A friend was diagnosed with a blood cancer. At the time, Deans didn’t know much about the diagnosis. But, in reading about her friend’s cancer, she learned how metastasizing tumor cells interact with platelets.
That’s when Deans had her “aha” moment: maybe the engineered platelets could also be put to work in preventing metastasizing tumor cells from spreading.
Now, with her New Innovator Award, Deans will pursue this novel approach by engineering platelets to carry potentially promising cancer-fighting proteins. In principle, they could be tailored to fight breast, lung, and various other cancer types. Ultimately, she hopes that platelets could be engineered to target and kill circulating cancer cells before they move into other tissues.
There’s plenty of research ahead to work out the details of targeting the circulating cancer cells and then testing them in animal models before this strategy could ever be attempted in people. But Deans is excited about the path forward, and thinks that platelets hold great promise to function as unique drug delivery devices. It has not escaped her notice that this approach could work not only for controlling the spread of cancer cells, but also in treating other medical conditions.
Reference:
[1] Genetic circuits to engineer tissues with alternative functions. Healy CP, Deans TL. J Biol Eng. 2019 May 3;13:39.
Links:
Metastatic Cancer (National Cancer Institute/NIH)
Deans Lab (University of Utah, Salt Lake City)
Deans Project Information (NIH RePORTER)
NIH Director’s New Innovator Award (Common Fund)
NIH Support: Common Fund; National Cancer Institute
Cool Videos: Heart Attack
Posted on by Dr. Francis Collins
Up next in our scientific film fest is an original music video, straight from the Big Apple. Created by researchers at The Rockefeller University, this song-and-dance routine provides an entertaining—and informative—look at how blood clots form, their role in causing heart attacks, and what approaches are being tried to break up these clots.
Before (or after!) you hit “play,” it might help to take a few moments to review the scientists’ description of their efforts: the key to saving the lives of heart attack victims lies in the molecules that control how blood vessels become clogged. This molecular biomedicine music video explains how ischemic injury can be prevented shortly after heart attack symptoms begin: clot blocking. The science is the collaborative work of Dr. Barry Coller of Rockefeller, Dr. Craig Thomas and his colleagues at the National Center for Advancing Translational Sciences (NCATS), and Dr. Marta Filizola and her Mount Sinai colleagues.
Links:
Laboratory of Blood and Vascular Biology, The Rockefeller University
Filizola Laboratory, Icahn School of Medicine at Mount Sinai
Center for Clinical and Translational Science, The Rockefeller University
Clinical and Translational Science Awards (NCATS/NIH)
NIH Common Fund Video Competition
NIH support: Common Fund; National Center for Advancing Translational Sciences
Cellular Shape-Shifters to the Rescue
Posted on by Dr. Francis Collins
Caption: Angular red blood cells, called polyhedrocytes, held together by platelets (blue) and fibrin protein (yellow).
Credit: John Weisel, University of Pennsylvania, Philadelphia
Just as superheroes often change their forms to save the day, so it seems do red blood cells as they mobilize to heal a wound. Red blood cells usually look like oval, bi-concave discs, but NIH-funded researchers recently discovered that they are actually talented shape-shifters.
Gene Signature Predicts Aspirin Resistance
Posted on by Dr. Francis Collins
Caption: New blood test of gene activity reveals who will respond to aspirin therapy and who won’t.
Source: Duke Medicine
About 60 million Americans take an aspirin a day to reduce the risk of strokes and heart attacks. But for 10 to 30% of those who follow this recommendation, this preventive therapy turns out not to offer any protection. An NIH-funded team, based at Duke University Medical Center, has discovered a set of blood markers that predict who will benefit from aspirin therapy and who will not [1].
First of all, I’ve got to tell you that acetylsalicylic acid, the scientific name for aspirin, is a pretty amazing drug. German chemist Felix Hoffmann synthesized the first commercial form of the drug more than a hundred years ago to treat headaches, minor aches and pains, and fever—and we’re still discovering nuances about how the drug works, for whom, and for which diseases.
