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Two grants will fund interdisciplinary research at the Beckman Institute for Advanced Science and Technology, including a look at how neurons and muscle cells communicate with each other and also to develop a drug delivery system for treatment of Alzheimer's disease.

The grant from the National Science Foundation will facilitate the study of how neurons and muscle cells communicate with each other.

My group is interested in engineering functional muscle and using it to assemble autonomous bioactuator systems.

The muscle engineered in vitro is not the same as the muscles in our body because the system does not have any innervating motor neurons. This project is to understand how we can facilitate the innervation of the neurons into the muscle."

Hyunjoon Kong, a Robert W. Schafer professor of chemical and biomolecular engineering

Kong's lab will collaborate with Gabriel Popescu, a professor of electrical and computer engineering, and Martha Gillette, a professor of cell and developmental biology. All are affiliated with the Beckman Institute.

In addition to studying how the neurons and muscle cells communicate, the Kong group will also look at the interaction between neurons and glial cells, which influence neuronal activity. "Although glial cells are not well characterized, they are known to provide certain signals that make the neurons transmit their electrical signals," Kong said.

"I will be working with Martha Gillette's group, who are experts in neurobiology and can guide us in what type of neural cells to look at," Kong said. "Popescu group members are experts at imaging intracellular events and we want to use their imaging techniques to demonstrate the interaction between the neurons and the muscle cells."

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Members of the Kong group hope that the study will enable them to understand how neurons can be reactivated in injured muscle, which can help improve the treatment of various neuromuscular disorders and acute muscle injuries.

The second grant, from the Alzheimer's Foundation, will fund research by the Kong group in collaboration with Hee Jung Chung, an associate professor of molecular and integrative physiology and Beckman Institute faculty member.

The grant will study how a drug that has the potential to treat Alzheimer's disease can be delivered into the body. The drug was developed to target tau proteins that, along with β-amyloid proteins, cause the disease. "Historically, researchers have been focused on treatments that reduce the β-amyloid proteins. However, a large group of patients do not respond to those treatments because the tau proteins are also responsible," Kong said.

The Kong group hopes to join the research effort that is now focusing on synthesizing nano-sized drug carriers that can target the tau protein. "The drug that targets tau proteins cannot be currently used because it is hydrophobic and therefore cannot dissolve in water," Kong said. "As a result, you cannot deliver it orally or through injection." The group will try to solve the problem by encapsulating the drug in a nanoparticle system that can be used to target the diseased regions of the brain.

Source:

Beckman Institute for Advanced Science and Technology

Using cutting-edge imaging technology, researchers at Massachusetts General Hospital (MGH) have shown that the brains of young men with autism spectrum disorder (ASD) have low levels of a protein that appears to play a role in inflammation and metabolism. This surprising discovery, which published online today in the journal Molecular Psychiatry provides an important new insight into the possible origins of ASD, which affects one in 59 children.

ASD is a developmental disorder that emerges in early childhood and is characterized by difficulty communicating and interacting with others. While the cause is unknown, growing evidence has linked ASD to inflammation of brain tissue, or neuroinflammation. One sign of neuroinflammation is elevated levels of a substance called translocator protein (TSPO), which can be measured and located in the brain using positron-emission tomography (PET) and anatomical magnetic resonance imaging (MRI). The MGH study, led by Nicole Zurcher, PhD, an investigator in MGH's Athinoula A. Martinos Center for Biomedical Imaging, was the first to use a new generation of PET "tracers," which more accurately detect TSPO, to examine the brains of people with ASD.

In the study, Zurcher and her colleagues scanned the brains of 15 young adult males (average age, 24) with ASD. The group included both high- and low-functioning subjects with varying degrees of intellectual abilities. For comparison, Zurcher's team scanned the brains of 18 healthy control subjects who were similar in age. The investigators hypothesized that the scans would show increased levels, or expression, of TSPO in subjects who have ASD.

"To our surprise, that's not what we saw," says Zurcher. Instead, the scans showed that the brains of males with ASD had lower levels of TSPO than those of the healthy subjects. In fact, the men with the most severe symptoms of ASD tended to have the lowest expression of TSPO. When the tests were repeated several months later, the pattern persisted. The brain regions found to have low expression of TSPO have previously been linked to ASD in earlier studies, and are believed to govern social and cognitive capacities such as processing of emotions, interpreting facial expressions, empathy, and relating to others. "We know these brain regions are involved in autism," says Zurcher.

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To understand this unexpected finding, Zurcher notes that TSPO does more than serve as a marker of inflammation. "It has multiple complex roles," she says, and some actually promote brain health. For example, adequate TSPO is necessary for normal functioning of mitochondria, which are the "power houses" in cells that produce energy. Earlier research has linked malfunctioning mitochondria in brain cells to ASD.

Zurcher and her colleagues next plan to study brains from deceased donors with the goal of determining which brain cells in people with ASD might experience mitochondrial dysfunction, which she says may well be occurring alongside neuroinflammation and other mechanisms to cause ASD.

Our study has generated new hypotheses that now need to be investigated. There's more work to be done."

Nicole Zurcher, PhD, investigator, MGH's Athinoula A. Martinos Center for Biomedical Imaging

Source:

Massachusetts General Hospital

Journal reference:

Zürcher, N.R., et al. (2020) [11C]PBR28 MR–PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder. Molecular Psychiatry. doi.org/10.1038/s41380-020-0682-z.

The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded new grants totaling $1.8 million to two University of Texas at Dallas scientists for their research related to lung and kidney cancers.

The Individual Investigator Awards are among 55 new grants totaling more than $78 million that the institute announced Feb. 19. To date, CPRIT has awarded $2.49 billion in grants to Texas research institutions and organizations through its academic research, prevention and product development research programs.

With the latest grants to the researchers in the School of Natural Sciences and Mathematics, UT Dallas has received nearly $18.5 million from CPRIT to support cancer studies.

CPRIT continues to be an important source of funding for efforts aimed at the prevention and treatment of cancer. The institute's ongoing support of basic research allows UT Dallas scientists to make important contributions toward the fundamental understanding of disease and the improvement of outcomes for cancer patients."

Dr. Joseph Pancrazio, vice president for research and professor of bioengineering at UT Dallas

Dr. Li Zhang, professor of biological sciences and the Cecil H. and Ida Green Distinguished Chair in Systems Biology Science, received $900,000 for lung cancer research. In previous studies, Zhang and her colleagues discovered that cells of the most common type of lung cancer — non-small cell lung cancer — consume substantially more oxygen than normal cells. The lung cancer cells also outpace their normal counterparts in synthesizing a critical chemical called heme, which helps transport and store oxygen. These elevated levels of oxygen and heme fuel tumor growth and progression.

With the new CPRIT grant, Zhang will use advanced imaging techniques in animal models to investigate whether drugs that target heme synthesis and uptake can be a successful strategy for suppressing lung tumors and improving the effectiveness of chemotherapy, radiotherapy and immunotherapy.

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Zhang previously received a CPRIT grant of $900,000 in 2015.

Dr. Jie Zheng, professor of chemistry and biochemistry and the Cecil H. and Ida Green Professor in Systems Biology Science, also received $900,000 for his research, which is aimed at improving the accuracy of computerized tomography (CT)- and fluorescence-guided kidney cancer surgery.

With more kidney cancers being diagnosed in the early stage, partial kidney removal is becoming an increasingly important treatment, in particular for those patients who have poor kidney function or cancer in both kidneys. In current clinical settings, CT is used first to noninvasively localize and stage kidney cancers, followed by fluorescence imaging of normal renal tissue to guide surgery. However, due to the limitations of current contrast agents, no significant improvement in reducing positive margin rates in kidney cancer surgery has been achieved, Zheng said.

Zheng's project will focus on developing a single material, based on gold nanoparticles, that can achieve high contrast in both CT and fluorescence imaging of kidney cancers. His approach takes advantage of the unique physiological microenvironment associated with kidney cancer in a way that allows the tumor margins to be more accurately differentiated during surgical removal. His nanoparticles also have the potential to effectively and selectively deliver anti-cancer drugs to tumors that cannot be treated surgically.

Zheng received three previous CPRIT grants in 2011, 2014 and 2016 totaling nearly $2.4 million.

Source:

University of Texas at Dallas

Emory Healthcare in Atlanta now has the nation’s first 5G-enabled healthcare lab.

The health system is collaborating with Verizon to develop and test 5G Ultra Wideband-enabled medical use cases at its Emory Healthcare Innovation Hub.

It comes on the heels of the U.S. Department of Veterans Affairs announcement earlier this month that it would launch the first 5G-enabled hospital. The VA’s Palo Alto Health Care System, which is an affiliate of Stanford University School of Medicine, also worked with Verizon to bring 5G technology online.

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Emory’s healthcare hub will test how 5G could enhance augmented and virtual reality (AR/VR) applications for medical training, enable telemedicine and remote patient monitoring and provide point-of-care diagnostic and imaging systems from the ambulance to the ER. 

With 5G, doctors should be able to perform tasks like creating holographic 3D anatomical renderings that can be studied from every angle and even projected onto the body in the operating room to help guide surgery, said Tami Erwin, CEO of Verizon Business Group.

The 5G network’s larger bandwidth, faster speeds, and ultra-low latency have the potential to help redefine patient care with real-time data analytics, giving researchers the ability to explore solutions such as connected ambulances, remote physical therapy, and next-generation medical imaging, according to Verizon.

Speed to data is critical to the digital evolution of health,” Scott Boden, MD, vice president for business innovation for Emory Healthcare, said in a statement.

“The healthcare industry, driven by value-based care and increased consumerization, is set for a paradigm shift that will put a much greater focus on connectivity and access to data,” Boden said. 

The Emory Healthcare Innovation Hub was set up in 2018 to improve patient care and provider experience by using cutting-edge health technology. The hub came about from a partnership between Emory Healthcare and Sharecare to use a demand-driven innovation approached developed with 11ITEN Innovations Partners to identify technology improvements with a focus on the end-user while having an impact on cost, quality, and patient outcomes.

The innovation hub works with nine strategic partners to focus on precision medicine, genetics, trauma/emergency medicine, orthopedics, obesity, and rural access to care through telehealth.

As part of the collaboration, Verizon will offer network and security services, project management, professional consulting services, and managed infrastructure and sit on the Emory Hub Executive Advisory Board.

Verizon operates five 5G Labs in the U.S. and one 5G Lab in London. The Emory Healthcare Innovation Lab is the first 5G lab Verizon has set up on-premises for a customer, and it will be part of an ongoing initiative to co-develop 5G-related use cases.

Modern anticancer therapies aim to attack tumor cells while sparing healthy tissue. An interdisciplinary team of researchers at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and FU Berlin has made important progress in this area: the scientists have produced tiny nanoparticles that are designed to specifically target cancer cells. They can navigate directly to the tumor cells and visualize those using advanced imaging techniques. Both in petri dishes and animal models, the scientists were able to effectively guide the nanoparticles to the cancer cells. The next step is to combine the new technique with therapeutic approaches.

The HZDR researchers start out with tiny, biocompatible nanoparticles made of so-called dendritic polyglycerols that serve as carrier molecules.

We can modify these particles and introduce various functions. For example, we can attach an antibody fragment to the particle that specifically binds to cancer cells. This antibody fragment is our targeting moiety that directs the nanoparticle to the tumor."

Dr. Kristof Zarschler, research associate at HZDR's Institute of Radiopharmaceutical Cancer Research

The target of the modified nanoparticles is an antigen known as EGFR (epidermal growth factor receptor). In certain types of cancer, such as breast cancer or head and neck tumors, this protein is overexpressed on the surface of the cells. "We were able to show that our designed nanoparticles preferentially interact with the cancer cells via these receptors," confirms Dr. Holger Stephan, leader of the Nanoscalic Systems Group at HZDR. "In control tests with similar nanoparticles that had been modified with an unspecific antibody, significantly fewer nanoparticles accumulated at the tumor cells."

The scientists intensively studied the nanoparticles' behavior both in cell cultures and in an animal model. For this purpose, they provided the nanoparticles with additional reporter characteristics, as Kristof Zarschler explains: "We used two complementary possibilities. In addition to the antibodies, we attached dye molecules and radionuclides to the nanoparticles. The dye molecule emits in the near infrared spectrum that penetrates the tissue and can be visualized with an appropriate microscope. The dye thus reveals where exactly the nanoparticles are located." The radionuclide, copper-64, fulfils a similar purpose. It emits radiation that is detected by a PET scanner (positron emission tomography). The signals can then be converted into a three-dimensional image that visualizes the distribution of the nanoparticles in the organism.

Excellent properties in living organisms

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Using these imaging techniques, researchers have been able to show that nanoparticle accumulation in the tumor tissue reaches maximum two days after administration to mice. The labelled nanoparticles are subsequently eliminated via the kidneys without being a burden for the body. "They are apparently ideal in size and properties," says Holger Stephan. "Smaller particles are filtered out of the blood in just a few hours and thus only have a short-term impact. If, on the other hand, the particles are too big, they accumulate in the spleen, liver or lungs and cannot be removed from the body via the kidneys and bladder." The interplay between the nanoparticles with an exact size of three nanometers and the attached antibody fragments evidently has a positive influence on the distribution and retention of the antibody in the organism as well as on its excretion profile.

In future experiments, the HZDR researchers want to test whether they can modify their system to carry other components. Kristof Zarschler describes the plans: "You can take these nanoparticles and functionalize them with an active substance. Then you can deliver a drug directly to the tumor. This might be a therapeutic radionuclide that destroys the tumor cells." It is also possible to attach antibody fragments specific for proteins other than EGFR to target different types of cancer.

Source:

Helmholtz-Zentrum Dresden-Rossendorf

Journal reference:

Pant, K., et al. (2019) Active targeting of dendritic polyglycerols for diagnostic cancer imaging. Small. doi.org/10.1002/smll.201905013.