NSF CAREER Award to fund professor’s research to predict blood clots

Binghamton University Assistant Professor Jifu Tan sees blood vessels as pipes. That's why his background in mechanical engineering translates so serendipitously to the body: The same laws and equations that govern how fluids move through pipes are the ones he now uses to study the formation of blood clots.

"If you look from the outside, you'll say, 'This is the biology. This is the physics. This is the math.' But if you look inside, we can find the same language to describe all of them," Tan said. "You can write it in terms of mathematical equations, conservation laws of mass, momentum and energy, all those kinds of things. That's why I'm interested in this. That's why I can apply the knowledge I had from fluid mechanics to study biological flow problems."

A recent addition to the faculty at the Thomas J. Watson College of Engineering and Applied Science's Department of Mechanical Engineering, Tan brings with him a prestigious National Science Foundation (NSF) CAREER Award. The award is granted to early-career academics with the potential to become future leaders in their respective fields.

Over $500,000 will be dedicated to funding Tan's project in modeling the formation and rupture of blood clots within the bloodstream - part of a larger effort to tackle one of the leading causes of death in the world, cardiovascular disease.

Our blood's ability to clot is a double-edged sword. It's necessary to heal cuts and form scabs that block off bleeding, but clots also play a prominent role in many potentially fatal medical conditions such as stroke, pulmonary embolisms or heart attacks.

Despite this, little is understood about how clots grow and react in live environments, because they're so challenging to observe. For example, blood coagulation is a very complicated process, with more than 40 distinct types of proteins that often have conflicting purposes interacting with one another every second. In addition, our hearts pump at different rates depending on what we do, whether we're walking, running, or sleeping, leading to unsteady velocities in the blood stream. Furthermore, everyone's vessels are different too, some stiffer and others more flexible.

Ultimately, it's not just blood flow that affects the formation and composition of blood clots, but also the clot itself which will influence how blood circulates.

"This is the complicated blood coagulation process," Tan said.

Tan aims to understand this complex system by developing multiscale modeling tools to better predict how blood clots and reacts in different bodily environments. Much of his research takes place virtually, utilizing powerful computers, machine learning and open-sourced codes to run faster and faster simulations of blood with different blood cell components.

Whether the length of a tiny capillary or the over 60,000 miles of vessels comprising the entire circulatory system, this tool aims to predict how a clot grows and responds in any individual's blood, with patient-specific models considering blood cells, platelet activation and adhesion, and blood flow.

"This is the multiscale model we're trying to do, to hopefully come up with better tools for patients," Tan said. "For example, we can create a patient-specific model based on their blood vessel scans: what their blood pressure is, what's the likelihood of that patient developing some clots in their bloodstream."

Calibrating such models requires intensive validation to ensure it represents real bodies and systems. To verify their numerical models of red blood cells, for example, Tan's team relied on experimental data simulating how far a red blood cell could stretch and deform under certain forces. They also plan to test flow in an actual 3D-printed model that physically mimics the human vascular system.

Tan collaborates with partners in the University of Pennsylvania to validate his data, as well as the Argonne National Laboratory to develop much larger-scale computational models that can handle millions of particles moving in flow.

What this project will produce is a tool that not only models clot growth in our circulatory system's networks, but also aids healthcare providers in determining the best courses of treatment for their patients. That could include surgery planning, Tan said, and figuring out which vessel to cut or not based on how much blood a patient might lose.

Tan also aims to educate future generations of STEM students on the skill at the heart of his project: programming.

"How do we ease the fear of programming for those new students? How do you motivate them? How do you engage them?" he said. "How do you make them fall in love with programming?"

To answer this, he has developed Advanced Computing and Communication Engineering Notebooks for Teaching, or ACCENT, which teaches students how to use Python to break down complicated-looking codes and build a foundation for programming through regular course work.

He also will be expanding outreach to K-12 students by organizing summer engineering camps and participating in STEM festivals, aiming to inspire younger generations - especially those historically underrepresented in STEM spaces - to become the future's engineers and scientists.

Tan's research encompasses other areas like drug delivery, high-performance computing and machine learning, keeping his feet planted in both engineering and medical worlds. But his interest in the conundrum of blood clotting - and the prominence of cardiovascular disease - began during his time as a postdoctoral researcher at the University of Pennsylvania.

"Think about this problem. It is highly multidisciplinary, spanning math, physics, biology and engineering, and involves components like fluid mechanics, plasma, blood cells, platelets, chemical reactions and a fibrin network. It's a dynamic process, so I feel like this problem is kind of complicated. It's not completely solved," he said. "That's why I feel maybe I can do something about that."

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