Abstract: Human, viruses, bacteria bacteriophages, and Holliday junctions use asymmetrical hexameric revolving biomotors to translocate their dsDNA genome without rotation, avoiding coiling and tangling. Rotation is an object turning around its axis, similar to the Earth rotating 24 hours per day. Revolution is the orbital turning around another object, similar to the Earth revolving around the Sun. Extensive fundamental studies on the RNA-geared phi29 DNA packaging motor have led to the development of four novel applications using the motor component as nano-biomaterials: (1) the hand-in-hand interaction of the hexametric motor pRNA led to the emergence of RNA nanotechnology; (2) precision motor channels as nanopore for single molecule sensing; (3) the sequential revolving motor with homo-multi-subunits inspires the discovery of highly potent drugs; and (4) discovery of the asymmetrical hexameric motor for the translocation of dsDNA genome of viruses, bacteria, and eukaryotes for new drug targets.
Human genome sequencing has revealed that the majority of non-protein-coding DNA encodes for non-coding RNAs, marking a paradigm shift that could indicate RNA therapeutics as the third milestone in pharmaceutical drug development. We have constructed a variety of RNA nanoparticles with defined shape, size, and stoichiometry that have been developed for diverse applications in nanotech. RNA is controllable in shape and stoichiometry, spontaneously self-assembled, inherently motile, and deformable, allowing for both spontaneous and specific cancer targeting without detectable toxicity. Arrow-tail RNA nanoparticles allow for targeted drug delivery to cancer cell cytosols via exosome surface display.
The phi29 biomotor includes a nano-channel with a voltage-controlled shutter to regulate channel size and motion direction, serving as a durable nano-electric, biomimetic rectifier nano-aperture. This channel has been manipulated to sense single DNA, RNA, and peptides with sensitivity in discriminating signal molecules with a change of a single chemical group.

Biography: Dr. Guo, a fellow of the National Academy of Inventors and a pioneer of RNA nanotechnology and held three endowed chair positions at three different prestigious universities, is currently Endowed Chair professor OSU, and the President of ISRNN. He received his Ph.D. from UM under Dwight Anderson and postdoctoral training at NIH/NIAID under Bernard Moss. He has been a Young Distinguish Faculty Scholar of Purdue where he was a director of NIH Nanomedicine Development Center. He, with Bernard Moss invented a novel method for the production of the vaccinia virus mRNA capping enzyme that is used currently as an essential component for the production of COVID-19 mRNA vaccine. He Guo has received many honors; including the most recent “Innovator of the Year” by OSU in 2021, the Induction as NAI fellow in 2023 and the OSU President Research Excellent Catalyst Award in 2024.

Abstract: In the last decades, advances in bone tissue engineering mainly based on osteoinduction and stem cell research. Only recently, new efforts focused on the micro- and nanoarchitecture needed to improve and accelerate bone regeneration. By the use of additive manufacturing, libraries of bone substitutes were produced and tested for the optimal pore size, filament dimension, or lightweight microarchitecture to treat bone defects and promote bone augmentation. To that end, we produced pore-based, filament-based and triply periodic lightweight-based scaffolds and tested them in a cranial defect and a bone augmentation model in rabbits.
For the production of scaffolds, we applied the CeraFab 7500 from Lithoz, a lithography-based additive manufacturing machine and studied tri-calcium phosphate- based and hydroxyapatite-based scaffolds. As in vivo test model, we used a calvarial defect and a bone augmentation model in rabbits. Histomorphometry and microCT analysis showed that optimal pore and filament designs for osteoconduction differ from the ones for bone augmentation. For triply periodic minimal surface lightweight microarchitectures, a single gyroid- and diamond-microarchitecture performs well in bone augmentation and cranial defect models. Small adjustments of filament-based microarchitectures orchestrate cell differentiation towards osteoblasts and facilitates angiogenesis.
In essence, we have identified the optimal triply periodic lightweight, pore-based and filament-based microarchitecture for bone augmentation purposes needed for the placement of dental implants and for cranial defects. We learned that the optimal pore-based and filament-based microarchitecture for bone augmentations differs from the best for the treatment of defects. Moreover, we saw that additive manufacturing appears as a promising tool for the production of personalized bone substitutes to be used in cranio-maxillofacial surgery, dentistry, and orthopaedics.

Keywords: Additive manufacturing, Bone substitute; Osteoconduction; bone augmentation Microarchitecture.

Biography: Franz Weber graduated from the University Konstanz (Germany) with a PhD in Biology/Muscle Biochemistry. He completed a 3-year postdoctoral training on muscle cell biology at Cornell University Medical College in New York City and served as a lecturer in the Department of Cell Biology and Anatomy. He spent the following two years at Biochemistry of the ETH Zurich working on the lipid uptake from the small intestine. In 1995, he joined the Department of Cranio-Maxillofacial and Oral Surgery at the University Hospital Zurich. Beside his obligations at the University of Zurich, he became Director of the European Technical Center of Inion Ltd in Cambridge (UK) in 2005 and occupied this position until 2009. His research encompasses additive manufacturing, bone substitutes, osteoconduction, bone morphogenetic proteins, delivery systems, epigenetics, bone and pulp tissue engineering. Franz E. Weber has authored 137 peer-reviewed research articles published in international journals amounting to more than 7234 citations, 16 patents, several review articles, book chapters, and an h-index of 40. He is member of TERMIS (Tissue Engineering international & Regenerative Medicine Society), IADR (International Association for Dental Research), DKG (German Ceramic Society), ACerS (The American Ceramic Society), and SSB+RM (Swiss Society for Biomaterials and Regenerative Medicine).
He is currently appointed as Professor of Craniofacial and Oral Biotechnology at the Center of Dental Medicine, member of the Medical and the Science Faculty of the University of Zurich.

Abstract: Phosphorylation networks intimately regulate mechanisms of response to therapies. Yet, mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. My lab has pioneered an innovative biochemical and analytical system to measure the functional state of kinase enzymes and their signaling circuits. Our technology and resource (named HT-KAM and PhosphoAtlas) provide access to an unexplored parameter with considerable potential to accelerate the discovery of actionable targets for functional precision medicine. Focusing on BRAF(V600E) metastatic colorectal cancer, we found mechanisms of intrinsic resistance to BRAF+EGFR inhibition in tumors, including the parallel compensatory activation of an auto-onco-crine COX2–SRC pathway that is clinically tractable and for which translation in clinical trial is under consideration. Furthermore, mapping the phospho-catalytic signatures of melanoma specimens identified RPS6KB1 and PIM1 as emerging druggable vulnerabilities predictive of poor outcome in BRAF(V600E) melanoma patients. Our results show that therapeutic resistance can be caused by the concerted upregulation of interdependent pathways. Our kinase activity-mapping system is a versatile strategy that innovates the exploration of actionable kinases for personalized medicine.

Selected References:
Olow and Chen, et al 2016 Cancer Research
Coppé, et al 2019 Nature Cell Biology
Kim, et al 2021 Science
Ruiz & Atreya, et al 2023 Nature Cancer
Chong, et al 2023 JCI
Feichtenschlager, et al 2024 Molecular Cancer

Biography: Dr. Coppé is an Associate Professor at UCSF. He received his PhD from UC Berkeley and the Lawrence Berkeley National Laboratory, where he studied cellular senescence, aging and cancer with Dr. Campisi. His group focuses on revealing the intracellular and extracellular molecular circuits that wire therapy-resistant tumors. He pioneered a kinome mapping system to measure the functional state of kinase enzymes and their signaling networks. His goal is to translate orthogonal modalities of treatment resistance into actionable vulnerabilities to restore therapeutic response and prevent treatment failure.

Abstract: As an important biomarker of neural aging, the brain age reflects the integrity and health of the human brain. Accurate prediction of brain age could help to understand the underlying mechanism of neural aging. In this study, a cross-stratified ensemble learning algorithm with staking strategy was proposed to obtain brain age and the derived predicted age difference (PAD) using T1-weighted magnetic resonance imaging (MRI) data. The approach was characterized as by implementing two modules: one was three base learners of 3D-DenseNet, 3D-ResNeXt, 3D-Inception-v4; another was 14 secondary learners of liner regressions. To evaluate performance, our method was compared with single base learners, regular ensemble learning algorithms, and state-of-the-art (SOTA) methods. The results demonstrated that our proposed model outperformed others models, with three metrics of mean absolute error (MAE), root mean-squared error (RMSE), and coefficient of determination (R2) of 2.9405 years, 3.9458 years, and 0.9597, respectively. Furthermore, there existed significant differences in PAD among the three groups of normal control (NC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD), with an increased trend across NC, MCI, and AD. It was concluded that the proposed algorithm could be effectively used in computing brain aging and PAD, and offering potential for early diagnosis and assessment of normal brain aging and AD.

Biography: Dr. Xufeng Yao works as a professor, doctoral supervisor, vice dean of the school of medical imaging, Shanghai University of Medicine and Health Sciences, China. Once, he received his bachelor in medical imaging from Shandong First Medical University, and graduated from Fudan University for his PhD in biomedical engineering, and was a post-doctoral student in optical engineering at University of Shanghai for Science and Technology, China. He was also appointed as a permanent member of the committee of life electronics branch of China institute of electronics society. His current research interest focuses on artificial intelligence in imaging and omics for medicine. He won about 10 funds of national science foundation of China, Shanghai natural science foundation, China postdoctoral foundation, innovation fund of Shanghai Education Commission, etc. Recently, he has published more than 40 academic papers and reviewed for some SCI journals and international conferences. Till now, he has trained above 20 graduate students.

Abstract: Hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) has similar nanostructure and chemical composition to bone, and is incorporated into bone remodeling process to be substituted with new bone after osteoclastic resorption of the HAp/Col. The HAp/Col porous body has already been used practical medicine in Japan. On the other hand, preventing implant associated infection (IAI) is important for success of surgical treatments. In order to minimize IAI for bone void fillers, the followings are considered to be necessary; 1. Cleanness of surgical operation circumstances, 2. Add antimicrobial property to materials, 3. Bone void fillers should be dissolved/resorbed in appropriate time. The first one depends on each hospital/country, but third one is fortunately cleared for the HAp/Col; therefore, we tried to add antimicrobial property to the HAp/Col utilizing gentamicin or silver nanoparticles (AgNPs). The HAp/Col soaked in gentamicin suspension adsorbed gentamicin sufficiently. Release profile showed gentamicin on the HAp/Col was released completely in 3 days which is considered acceptable for the HAp/Col because incorporation of the HAp/Col into bone remodeling process starts in 5 days after implantation. Gentamicin added to the HAp/Col paste inhibited hardening process when its concentration was too high. Silver nanoparticles also adsorbed on the HAp/Col sufficiently. Gentamicin- and AgNPs-loaded HAp/Col indicated good antimicrobial activity and showed no cytotoxicity in the appropriate range of loading. These antimicrobial HAp/Cols are expected to be better bone void fillers.
Keywords: Hydroxyapatite, collagen, bone-like nanocomposite, bone-void fillers, antimicrobial property

Biography: Prof. Masanori Kikuchi had gotten his Ph.D. degree from Waseda University, Japan on March 1995 by the research on cation exchanged hydroxyapatites. He joined National Institute for research in Inorganic Materials (now it changed National Institute for Materials Science, NIMS, by merger with National Research Institute for Metal) in 1995 and promoted as a group leader of Bioceramics Group in 2007. After Joining NIMS, he worked on calcium phosphate based bioceramics and composite biomaterials for bone regeneration. One of his main topics is hydroxyapatite/collagen bone-like nanocomposite (HAp/Col) and its first paper on Biomaterials 2001 has been cited more than 800 in SCOPUS (more than 1,100 in Google Scholar). The HAp/Col porous body is sold in Japan from 2013 and widely used in both orthopedic and dental fields. He also works on functionalization of biominerals from sea urchin, antithrombogenic surface treatment of Ti and international standardization of bioceramics.
He is a professor at the University of Tsukuba, visiting professor at Hokkaido University and guest professor at Okayama University. He also serves for ISO as a convenor of ISO/TC 150/SC 1/WG 3 from 2011 and head of Japanese delegation for ISO/TC 150 from 2023. He win several awards including Ichimura Academic Award from The New Technology Development Foundation and 74th Award of The Ceramic Society of Japan.