Now in its third year, the research seed grant program at the Beckman Institute for Advanced Science and Technology will fund two research projects beginning in 2025. Each research team will receive up to $75,000 per year for the next two years.

Two interdisciplinary teams hope their projects, enabled by seed funding from the Beckman Institute, will earn external funding from competitive agencies like the American Heart Association, European Research Council, National Science Foundation and National Institutes of Health.

Harnessing cold plasma technology to address critical limb ischemia

One research team will introduce cold plasma technology to the Beckman Institute to develop cell-free therapies that promote vascular repair and improve limb function in patients with critical limb ischemia.

Critical limb ischemia is the most advanced stage of peripheral artery disease and affects millions of people in the United States. Severe artery blockages reduce blood flow to the limbs, ultimately causing chronic wounds and pain and increasing the chances of limb amputation and death.

Although current treatments exist, including revascularization surgery and pharmacotherapy, these options often fall short for patients with diabetes and extreme cases of vascular damage.

Modern cell-based therapies show promise in combating these extreme cases but still have many limitations such as poor cell survival and immune rejection.

The Beckman research team, led by Wawrzyniec Dobrucki, Marni Boppart and J. Gary Eden, proposes to use cold plasma technology to enhance tissue regeneration and repair, ultimate promoting cell survival and discouraging immune rejection.

Dobrucki is an associate head and professor of bioengineering and the Neil and Carol Ruzic Scholar of biomedical and translational sciences at the University of Illinois Urbana-Champaign. Boppart is the Saul J. Morse and Anne B. Morgan Professor of the College of Applied Health Sciences as well as an associate head and professor of kinesiology and community health. Eden is a professor of electrical and computer engineering.

The team also includes Iwona Dobrucka, the assistant director of the Beckman Institute Molecular Imaging Laboratory, Catherine Applegate and Guillermo Monroy, both Beckman Institute postdoctoral fellows, Goodluck Okoro, a doctoral student in bioengineering, and Dr. Navid Adoni, a clinical interventional cardiologist at Carle Foundation Hospital.

Together, the researchers will investigate using cold plasma-primed extracellular vesicles to advance vascular repair and tissue regeneration in limb ischemia.

Extracellular vesicles, or EVs, are like tiny messengers released from cells in the body. They travel between cells and are used for communication, immune responses and tissue regeneration and development.

Previous research has shown that cold plasma creates reactive oxygen and nitrogen ions that interact with biological tissues to influence cellular processes and enhance wound healing.

"What's truly exciting is not just using EVs as a novel treatment, but enhancing their therapeutic power with cold plasma, the "fourth state" of matter. No one has ever attempted to use cold plasma to transform EVs into a therapy for peripheral arterial disease, making this study a bold first in the field," Dobrucki said.

The team will use low-dose cold plasma to prime, or stimulate, pericytes, cells that are essential for vascular stability and repair, to create EVs with enhanced regenerative properties.

These enhanced EVs are expected to counteract the detrimental effects of critical limb ischemia that often impedes vascular regeneration treatments.

"Extracelluar vesicles show exceptional promise in treating a wide variety of diseases and degenerative conditions. I believe EV therapies represent the future of regenerative medicine," Boppart said.

In a collaborative effort that combines expertise from biomedical engineering, plasma physics, physiology and pre- and clinical cardiology fields, the team hopes their work will lead to more effective and less invasive intervention options to treat cardiovascular diseases.

Using novel ultrasound imaging to investigate thalamus function in the brain

In telecommunications systems, operators work at relay centers connecting line to line or receiving and transmitting information from one location to another.

In the brain, the thalamus is often referred to as the relay center. It functions by flowing sensory and motor information to different cortical regions, or areas of the cerebral cortex, the largest part of the brain that is responsible for higher-level cognitive thinking, planning and sensory perception.

While we have a good understanding of how telecommunication relay centers function, the thalamus has been incredibly difficult to study because of its location deep within the brain.

Beckman researchers Dr. Daniel Llano, Michael Oelze and Sepideh Sadaghiani, however, are proposing to use a novel form of functional ultrasound imaging to record real-time activity in the thalamus.

“This work is important because it will shed light about a brain region, the thalamus, that has been notoriously difficult to study. Gaining a better understanding of how the thalamus dynamically modulates long-range communication in the brain may shed light about disorders of network function such as autism, schizophrenia and Alzheimer’s Disease,” Dr. Llano said.

With combined expertise in optical brain imaging, thalamocortical physiology, functional ultrasound imaging and network analysis of brain function, the leading researchers will work with two postdoctoral researchers, Nathiya Vaithiyalingam Chandra Sekaran and Zhenchang Kou, and graduate student Leykza Carreras-Simons from the Llano, Oelze and Sadaghiani laboratories, respectively.

The project’s two main goals are to measure thalamic activity after sensory and cortical stimulation and to determine the impact of thalamic silencing on the dynamics of long-range cortical communication.

Neurons, specialized brain cells that transmit information, in the thalamus receive “bottom-up” inputs from the outside sensory world and “top-down” inputs from the cerebral cortex.

It has been thought that top-down inputs interact with an inhibitory region of the thalamus, called the reticular nucleus, which narrows the area of activation and enhances the center field of activation in the thalamus.

Think of using binoculars. The lenses decrease the size of the field of view but enhance the object being looked at. In a similar manner, a broader area of activation in the thalamus from bottom-up input only will be narrowed and refined when bottom-up input is combined with top-down input.

Because of the spatial limitations of previous imaging technology, the theory of this shift in thalamic activation has not yet been tested or observed.

“It is exciting to apply network science approaches to a new data modality and focus on the thalamus. Most prior network neuroscience studies have focused on the cortex and miss the critical role of the thalamus in orchestrating cortical interactions,” Sadaghiani said.

Recent advancements in functional ultrasound technology, however, have greatly increased its spatial resolution, a key development that the team hopes to take advantage of.

Using functional ultrasound, which now has spatial resolution on the order of tens of microns, the team will image the thalamus while stimulating auditory regions of the thalamus, using both bottom-up sensory stimuli and top-down input. The group plans to image and measure the shift in size from a broad area of activation in the thalamus to a narrower one when both inputs are stimulated.

The second objective is to understand long-range cortical communication. Prior research has shown strong direct and indirect connectivity between cortical areas of the brain, mediated through the thalamus.

Working again with the auditory system, the researchers propose to silence, or de-functionalize, the thalamus to determine if the connectivity between the primary auditory cortex and secondary auditory cortex is altered or diminished.

Understanding the function and nuances of long-range cortical communications is of high clinical importance. Many long-range communication networks are dysregulated in disorders such as autism, schizophrenia and Alzheimer’s Disease.

"I think we are just beginning to integrate new high spatial resolution imaging technologies like ultrasound with improving our understanding of brain function. Future research could utilize these tools to better understand the underlying disease mechanisms related to neurological diseases and disorders. We will continue to pursue external funding opportunities, both federal and private foundations, to examine these and other questions related to brain health," Oelze said.

Llano, Oelze and Sadaghiani anticipate that their findings will provide valuable insights for neuroscience, clinical practice, and the continued development of medical interventions designed to treat a range of disorders where thalamic and cortical regions are dysregulated.