Picture of person in lab looking through microscope with two other lab members standing near. Words Annual Report 2024

Picture of Lahann Words: 2024 has been an exciting year for BI. Our hard work and determination have been evident with nearly $36MM in FY24 research expenditures. This year, Jan Hu, BDS, PhD, Sasha Cai Lesher-Pérez, PhD, and Matthew Willsey, MD, PhD, joined BI as core faculty, bringing our total faculty count to 35. These core faculty members are going above and beyond to advance research in advanced materials and drug delivery, bioinnovations in brain cancer, cell and tissue engineering, nanotechnology, neural engineering, and single-cell technologies. When it comes to innovation, BI faculty continue to lead the way. In FY24, we reported 33 invention disclosures, bringing our cumulative total to 296 since the establishment of BI in 2012. We also had 7 new U.S. patents issued and 2 new option and license agreements executed. These remarkable figures are a testament to the entrepreneurial spirit we nurture here at BI. We are continually proud of the efforts and contributions of our students and trainees. Their participation as featured presenters at the BI Research Day demonstrated their commitment to advancing translational research. We will continue to host a spectrum of activities such as the BI Distinguished Lectureship, BI BIONIC events, the summer undergraduate research internship program (SURi), journal clubs, research day, and faculty coffee hours. These events are designed to foster immersive, inclusive, and insightful discussions that enhance collaborations. We are looking forward to an even more productive 2025. Sincerely, Lahann

Exploring Science BI hosts several events each year to create opportunities for researchers to explore scientific topics, showcase their specialties, and engage in educational activities. Research Day Picture of poster session. Researchers present innovative and interdisciplinary work taking place at BI. Research is showcased by presenting nanotalks, micro posters, and full posters. 2024 Winners: Micro Poster: Miguel Ortiz-Lopez, April Kim, Kate Kaplin Full Poster: Shi Bei (Ashley) Tan, Aadil Javed, Christina Sheckler Nanotalk: Trevor Teague, Mohammad Asadi Tokmedash, Abha Kumari, Zhibek Bekezhankyzy Distinguished Lecturer: Dr. Rizwan Romee Photo of Dr. Romee talking to students Dr. Rizwan Romee, Associate Professor of Medicine at Harvard Medical School and Director of the Haploidentical Stem Cell Transplantation Program at Dana-Farber Cancer Institute Dr Romee, presented “Novel Cytokine Engineering Approaches for Enhanced Immunotherapy of Cancer." During his visit, he met with students to discuss navigating their career paths and had one-on-one meetings with faculty to collaborate on various scientific topics.

FY 2024 Research In Numbers $35,710,922 in Research Expenditures 277 Proposals Summited 60 Proposals Awarded 33 Invention Disclosers 7 Issued U.S, Patents 2 New Companies Launched 2 Option & Licensing Agreements 185 Publiations

Experiencing Breakthroughs Every year BI core faculty release groundbreaking and influential papers that drive scientific progress and shape future technological developments. Here are a few selected examples. BI Faculty: Peter Tessier, PhD Title: Computational optimization of antibody humanness and stability by systematic energy-based ranking DOI: 0.1038/s41551-023-01079-1 Abstract: Conventional methods for humanizing animal-derived antibodies involve grafting their complementarity-determining regions onto homologous human framework regions. However, this process can substantially lower antibody stability and antigen-binding affinity, and requires iterative mutational fine-tuning to recover the original antibody properties. Here we report a computational method for the systematic grafting of animal complementarity-determining regions onto thousands of human frameworks. The method, which we named CUMAb (for computational human antibody design; available at http://cumab.weizmann.ac.il), starts from an experimental or model antibody structure and uses Rosetta atomistic simulations to select designs by energy and structural integrity. CUMAb-designed humanized versions of five antibodies exhibited similar affinities to those of the parental animal antibodies, with some designs showing marked improvement in stability. We also show that (1) non-homologous frameworks are often preferred to highest-homology frameworks, and (2) several CUMAb designs that differ by dozens of mutations and that use different human frameworks are functionally equivalent. Link to read paper and image from the paper.

Experiencing Breakthroughs BI Faculty: Anthony Rosenzweig, MD Title: Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human DOI:10.1126/scitranslmed.adi0077 BI Faculty: Maria Castro, PhD & Anthony Rosenzweig, MD Title: Placental senescence pathophysiology is shared between peripartum cardiomyopathy and preeclampsia in mouse and human DOI:10.1126/scitranslmed.adi0077 Abstract: Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives his process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy. Link to the paper Image from the paper

Experiencing Breakthroughs BI Faculty: Nicholas Kotov, PhD and Sunitha Nagrath PhD Title: Chiroptical detection and mutation analysis of cancer-associated extracellular vesicles using microfluidics with oriented chiral nanoparticles DOI: 10.1016/j.matt.2024.09.005 Summary: Cancer-cell-secreted small extracellular vesicles, known as exosomes, represent a rapidly emerging family of cancer biomarkers. However, the current protocols for exosome analysis require complex equipment and lengthy procedures, which prevents their broad utilization for cancer diagnosis. We have engineered plasmonic gold nanoparticles Summary: Cancer-cell-secreted small extracellular vesicles, known as exosomes, represent a rapidly emerging family of cancer biomarkers. However, the current protocols for exosome analysis require complex equipment and lengthy procedures, which prevents their broad utilization for cancer diagnosis. We have engineered plasmonic gold nanoparticles combining molecular and nanoscale chirality and have demonstrated that such nanoparticles in self-assembled films in a microfluidic device can isolate and analyze exosomes directly from blood plasma due to marker-specific chiroptical responses and volumetric electromagnetic resonance. Cancer exosomes can be distinguished from those from healthy donors by their giant polarization rotation signatures, and the observed dependence of plasmonic resonances on mutations of epidermal growth factor receptor suggests the possibility of in-line mutation/deletion analysis of protein cargo based on molecular chirality. The present microfluidic chips eliminate ultracentrifugation and improve the sensitivity and detection speed by at least 14 times and 10 times, respectively, enabling the rapid liquid biopsy of cancer. Link to read the paper Image from the paper

Experiencing Breakthroughs BI Faculty: Joerg Lahann, PhD and Anna Schwendeman PhD Title: Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles DOI:10.1073/pnas.2312082121 Abstract: Despite decades of intense research, glioma remains a disease for which no adequate clinical treatment exists. Given the ongoing therapeutic failures of conventional treatment approaches, nanomedicine may offer alternative options because it can increase the bioavailability of drugs and and alter their pharmacokinetics. Here, a new type of synthetic protein nanoparticles (SPNPs) is reported that allow for effective loading and controlled release of the potent cancer drug, paclitaxel (PTX) – a drug that so far has been unsuccessful in glioma treatment due to hydrophobicity, low solubility, and associated delivery challenges. SPNPs are prepared by electrohydrodynamic (EHD) jetting of dilute solutions of PTX-loaded albumin made by high-pressure homogenization. After EHD jetting, PTX SPNPs possess a dry diameter of 165 ± 44 nm, hydrated diameter of 297 ± 102 nm, and a zeta potential of −19 ± 8 mV in water. For the SPNP formulation with a total PTX loading of 9.4%, the loading efficiency is 94%, and controlled release of PTX is observed over two weeks (6% burst release). PTX SPNPs are more potent (68% lethality) than free PTX (45% lethality using 0.2% dimethyl sulfoxide). PTX SPNPs in combination with IR show a significant survival benefit in glioma-bearing mouse models, avoid adverse liver toxicity, and maintain a normal brain architecture. Immunohistochemistry reveals a dramatic tumor size reduction including 40% long-term survivors without discernible signs of tumor. Using flexibly engineered SPNPs, this work outlines an efficient strategy for the delivery of hydrophobic drugs that are otherwise notoriously hard to deliver. Link to paper Image from the paperCreating Collaborations Bioengineering in Brain Cancer Challenge This year the BIBC Program and the Biointerfaces Institute co-hosted the Bioengineering in Brain Cancer Challenge to explore new ideas and catalyze interdisciplinary collaborative research to address the challenges in brain cancer therapy. Winners of the Challenge Funds: “Spatiotemporal Imaging and Analysis of Cell Force in Migrating Oncostreams” Co-PIs: Changyang Linghu, Ph.D, Assistant Professor, Department of Cell and Developmental Biology. Member, Michigan Neuroscience Institute and SCSAP Program. Pedro Lowenstein, MD, PhD, Professor, Department of Neurosurgery, Cell and Developmental Biology, and Biomedical Engineering. “Neuromodulation of Glioblastoma” Co-PIs: James D. Weiland, PhD, Professor of Ophthalmology and Biomedical Engineering. Dawen Cai, PhD, Associate Professor Cell & Developmental Biology, Associate Professor, Biophysics. Maria G. Castro, PhD, R. C. Schneider Collegiate Professor of Neurosurgery; Professor of Cell & Developmental Biology. Pedro Lowenstein, MD, PhD, Professor, Department of Neurosurgery, Cell and Developmental Biology, and Biomedical Engineering. Cynthia Chestek, PhD, Associate Professor, Department of Biomedical Engineering (primary), Department of Electrical Engineering, and the Robotics Institute. Picture from event and picture of Brain Link to website Heading 35 Faculty from Four Schools Researching Six Clusters Image for each cluster and the cluster names: Adaptive Materials & Drug Delivery Bioinnovations in Brain Cancer Cell & Tissue Engineering Nanotechnology Neural Engineering Single Cell Technologies Graph with percent of faculty in each school School of Dentistry 6% College of Engineering 41% School of Medicine 39% College of Pharmacy 14% Picture of Jan Hu Jan Hu, BDS, PhD Title: Samuel D Harris Collegiate Professor of Dentistry and Professor of Dentistry, Department of Biological and Materials Science, School of Dentistry. Lab Description: The Simmer Hu laboratory studies tooth development, focusing on the human genetics of developmental defects of the dentition and using gene edited mouse models to understand how proteins encoded by genes function during normal tooth development and how their mutations lead to failures in such process. The ultimate goal of our research is to apply scientific discoveries toward devising therapeutic measures for human disorders and diseases involving teeth. Picture of Sasha Cai Lesher-Pérez Sasha Cai Lesher-Pérez, PhD Title: Assistant Professor of Chemical Engineering and Assistant Professor of Biomedical Engineering, College of Engineering. Lab Description: The Lesher-Pérez lab is interested in how the dynamics of biomolecules, such as hormones, circulating through our body impact human health and disease. Their mission is to develop technologies and strategies to understand, parametrize, and treat the impacts of biomolecular rhythm dysregulation in humans. Picture of Matthew Willsey Matthew Willsey, MD, PhD Title: Assistant Professor of Neurosurgery, Medical School and Assistant Professor of Biomedical Engineering, Medical School and College of Engineering. Lab Description: The Willsey lab focuses on intracortical brain-computer interfaces (iBCIs) as a potential therapy for paralysis. They aim to help develop an entry-level iBCI system for paralyzed human patients to address needs that cannot be met by today’s assistive technologies. Their research focuses on developing multi-effector control for fine motor movements, digital interfaces using non-linear decoding algorithms, and novel approaches to expand functionality and account for neural instability.

Building Community Summer Ice Cream Social We host an annual networking ice cream social to celebrate lab clean up week. Picture of Ice Cream Social. BI Mindful Minutes with Nico the Therapy Dog Nico, the therapy dog, paid a visit to BI at the end of the winter term to help our community unwind and recharge. Picture of BI community playing with Nico the therapy dog. BIONIC Summer BBQ The Biointerfaces Interlaboratory Committees (BIONIC), an organization of graduate, postdoctoral, and staff researchers from multiple BI research groups, focuses on enhancing interlaboratory connections. The BIONIC team plans major scientific, outreach, career development, and social engagement initiatives. The BIONIC events offer opportunities for the entire community to enable researchers to interact and enhance the flow of knowledge across disciplines, labs, and individuals Picture of a student grilling hamburgers.

Accelerating Innovation Innovation Fellowship The Innovation Fellowship is a full-time position for up to two years. The program offers a unique opportunity for Fellows to be embedded within the BI research and translational ecosystem to explore research commercialization. 2024 BI Innovation Fellow Ruby Miller, PhD Ruby earned her PhD in Chemistry from the University of Michigan and holds a certificate in Science, Technology, and Public Policy from the Ford School of Public Policy. She is passionate about advancing translational research, fostering science communication, and driving commercialization to create positive, community-wide impact. Highlights of the projects Ruby completed this year: Conducted market analysis and drafted key sections for SBIR grant applications. Led customer discovery for a BI startup, leveraging insights from the FFMI fastPACE training program. Promoted BI technologies and facilitated industry connections through networking and conference participation. Mapped the entrepreneurial ecosystem and advanced BI’s presence within Ann Arbor’s life sciences commercial sector. Picture of Ruby Miller Link to more about Ruby

Growing Futures 2024 SURi Program BI offers a unique internship for undergraduate scholars to be embedded within BI’s research and translational ecosystem. Working with BI faculty mentors and graduate students, scholars conduct intensive summer research work to gain valuable skills. The goal is for students to explore biomedical, translational, or clinical research interests, and its related career opportunities. Picture of 2024 SURi Students Parkridge Community Center This summer BI and BIBC partnered with Washtenaw Community College to offer stem programing to children 6-12 years old. Picture of BIONIC students teaching kids at Parkridge. Harris High School in Likwakwanda, Malawi BI partnered with BIONIC to support STEM in a school in Malawi. Picture of teacher and students from Harris High School.

BI Logo Vision To solve society’s most complex and pressing public health challenges by fostering cross-disciplinary technological breakthroughs transcending discipline-based departments of life sciences, physical sciences, engineering, and medicine. Mission The University of Michigan (U-M) Biointerfaces Institute (BI) established in 2012 breaks down disciplinary silos, provides a barrier-free environment, and brings together researchers from life and physical sciences to ignite new discoveries and accelerate the delivery of technologies to impact human health. Our mission extends beyond building interdisciplinary research connections, we are also committed to open and inclusive environments that strengthen, celebrate, and support our community of learners, researchers, faculty, and staff. External advisroy Board Bill Brinkerhoff, MBA/MSIOE Valina L. Dawson, PhD Carl L. Gordon, PhD, CFA Samir Mitragotri, PhD Natasha Shervani, SCB Mark Trudeau, BSE, MBA Executive Committee Maria Castro, PhD Evan Keller, DVM, PhD Nicholas Kotov, PhD Joerg Lahann, PhD Sunitha Nagrath, PhD Elizabeth Herness Peters, PhD Steven Schwendeman, PhD James Weiland, PhD Max Wicha, MD 2800 Plymouth Road, Building 10, A175, Ann Arbor, MI 48109 P: 734.763.7924 E: Biointerfaces@umich.edu

 

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2024 Annual Report