Tag: nanomedicine

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2024 Solomon R. Pollack Awards for Excellence in Graduate Bioengineering Research

The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania is proud to recognize the work of four outstanding graduates in Bioengineering: William Benman, Alex Chan, Rohan Palanki and Sunghee Estelle Park. 

Read more about the 2024 Solomon R. Pollack awardees and their doctoral research below.

William Benman

Dissertation: “Remote control of cell function using heat and light as inputs”

Will conducts research in the lab of Lukasz Bugaj, Assistant Professor in Bioengineering, focusing on reprogramming cells so that their basic functions can be regulated artificially using heat and/or light as inputs. The goal of this work ranges from clinical applications, such as localized activation of cell therapies within patients via application of heat, to biological manufacturing, using light to activate production of valuable biologics during key phases of a cell’s life cycle. He earned his undergraduate degree in biomedical engineering from Boston University, where he graduated summa cum laude. At BU, he worked in the lab of Wilson Wong, where he was introduced to synthetic biology. During that time, he worked to develop a genetic logic framework that would allow cells to integrate chemical signals, such that each combination of signals would lead to a different, user-defined combination of genes being expressed. Outside of the lab, Benman enjoys baking and sharing his treats with lab members. He mentored the 2021 Penn iGEM team, which recently published their work in Communications Biology. After graduation, he will start a postdoctoral fellowship in Mikhail Shapiro’s lab at Caltech, where he plans to explore electrogenetics, focusing on how to co-opt electrically active cell types to transmit biochemical information out of the body. He is interested in researching ways to get cells to talk to electronic devices and vice/versa for two way communication, especially in the context of patient monitoring and precision therapies. 

“Will’s Ph.D. work broke new ground across several fields, discovering how certain proteins sense temperature, engineering those proteins for on-demand control of human cells, and building devices to allow us to communicate with cells with precision,” says Bugaj. “He has managed these accomplishments while elevating those around him through mentorship, including of graduate students, scores of undergraduates, and even grade-school students in the community. I am immensely proud of Will and what he has accomplished and am gratified by the recognition from the Sol Pollack award.”

Alex Chan

Dissertation: “Engineering small protein based inhibitors and biodegraders for cytosolic delivery and targeting of the undruggable proteome”

Alex conducts research in the lab of Andrew Tsourkas, Professor in Bioengineering and Co-Director, Center for Targeted Therapeutics and Translational Nanomedicine (CT3N). His research focuses on developing novel cancer therapeutics by engineering protein scaffolds so that they can be efficiently delivered into cells using lipid nanocarriers. These proteins can either behave as oncogenic inhibitors or be imbued with E3 domains for targeted protein degradation. He graduated from The Pennsylvania State University in 2018 with a B.S in Biomedical Engineering. There, he conducted undergraduate research on photo-activated silver nanoparticle miRNA delivery systems and wrote his senior honors thesis on this topic. At Penn, Alex served as a wellness co-chair within GABE (the Graduate Association of Bioengineers) and was awarded a graduate research fellowship program award by the National Science Foundation (NSF GRFP). In his spare time, Chan loves to cook and explore the local restaurant scene (and he thinks Philly is one of the most vibrant food meccas in America). Post-graduation, he plans to explore Asia before starting as a Senior Scientist in the biopharma industry. He intends to continue working on novel biologics-based medicines for unmet medical needs.

“I cannot think of anyone more deserving of this award than Alex,” says Tsourkas. “He not only demonstrates all of the traits that we love to see in our most successful Ph.D. students — intelligence, hard work ethic, and perseverance — but Alex has also exhibited a level of scientific independence that is beyond his years. I cannot wait to see what Alex achieves in the future.”

Rohan Palanki

Dissertation: “Ionizable lipid nanoparticles for in utero gene editing of congenital disease”

Rohan completed his B.S. in Bioengineering from Rice University in 2019 and subsequently matriculated into the Medical Scientist Training Program (M.D./Ph.D.) at the University of Pennsylvania. He conducted his doctoral research as an NIH Ruth L. Kirschstein Pre-Doctoral Fellow in the laboratories of Michael J. Mitchell, Associate Professor in Bioengineering, and William H. Peranteau, Associate Professor of Surgery at CHOP. After defending his thesis in 2024, he returned to medical school to complete his clinical training. He plans to pursue a career as a physician-engineer, conducting translational research at the intersection of biomaterials and genomic medicine. Outside of the lab, Palanki enjoys exploring new restaurants in Philadelphia and cheering on Philadelphia sports teams.

“Rohan pioneered new lipid nanoparticle gene editing technology in the lab that can treat deadly childhood diseases before a child is ever born,” says Mitchell. “Rohan is extremely deserving of this award, and I cannot wait to see what he accomplishes as a physician scientist developing new biomaterial and drug delivery technologies for pediatric applications.”

Sunghee Estelle Park

Dissertation: “Engineering stem cells and organoids on a chip for the study of human health and disease”

Sunghee Estelle Park earned her BMSE and MSME from Korea University and her Ph.D. in Bioengineering at the University of Pennsylvania, graduating in July 2023. She conducted doctoral research in the BIOLines Lab of Dan Huh, Associate Professor in Bioengineering. Her Ph.D. research combined principles in developmental biology, stem cell biology, organoids, and organ-on-a-chip technology to develop innovative in vitro models that can faithfully replicate the pathophysiology of various human diseases. Her doctoral dissertation presented engineering approaches to create stem cell derived three-dimensional (3D) miniature models of human organs on a chip that mimic the physiology and function of living human tissues. Park was appointed Assistant Professor of Biomedical Engineering in the Weldon School of Biomedical Engineering at Purdue University beginning January 2024. Her research lab focuses on using engineered tissues and organoid models to understand how biomechanical and biochemical cues direct stem cell differentiation, maturation, and function during development and disease progression, with a particular emphasis on the lung and intestine. 

“With her deep knowledge, extensive experience, and leadership, Estelle led the major undertaking of harnessing the power of microengineering technologies to create more in vivo-like culture environments in my group, and she played a central role in demonstrating the proof-of-concept of generating organoid-based in vitro models that enable new capabilities for studying complex human diseases and developing new therapeutics,” says Huh. “I am extremely proud of her tremendous accomplishments as a trailblazer in this emerging area and have every confidence that her work as an independent investigator will continue to make great contributions to advancing the field.”

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Penn Bioengineers Awarded 2023 “Accelerating from Lab to Market Pre-Seed” Grants

Congratulations to the members of the Penn Bioengineering community who were awarded 2023 Accelerating from Lab to Market Pre-Seed Grants from the University of Pennsylvania Office of the Vice Provost for Research (OVPR).

Andrew Tsourkas, Ph.D.

Three faculty affiliated with Bioengineering were included among the four winners. Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), was awarded for his project titled “Precise labeling of protein scaffolds with fluorescent dyes for use in biomedical applications.” Tsourkas’s team created protein scaffold that can better control the location and orientation of fluorescent dyes, commonly used for a variety of biomedical applications, such as labeling antibodies or fluorescence-guided surgery. The Tsourkas Lab specializes in “creating novel targeted imaging and therapeutic agents for the detection and/or treatment of diverse diseases.”

Also awarded were Penn Bioengineering Graduate Group members Mark Anthony Sellmeyer, Assistant Professor in Radiology in the Perelman School of Medicine, and Rahul M. Kohli, Associate Professor of Medicine in the Division of Infectious Diseases in the Perelman School of Medicine.

From the OVPR website:

“Penn makes significant commitments to academic research as one of its core missions, including investment in faculty research programs. In some disciplines, the path by which discovery makes an impact on society is through commercialization. Pre-seed grants are often the limiting step for new ideas to cross the ‘valley of death’ between federal research funding and commercial success. Accelerating from Lab to Market Pre-Seed Grant program aims to help to bridge this gap.”

Read the full list of winning projects and abstracts at the OVPR website.

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Penn Engineers Develop a New Method that Could Enable a Patient’s Own Antibodies to Eliminate Their Tumors

Tsourkas
Andrew Tsourkas, Ph.D.

One of the reasons that cancer is notoriously difficult to treat is that it can look very different for each patient. As a result, most targeted therapies only work for a fraction of cancer patients. In many cases, patients will have tumors with no known markers that can be targeted, creating an incredible challenge in identifying effective treatments. A new study seeks to address this problem with the development of a simple methodology to help differentiate tumors from healthy, normal tissues.

This new study, published in Science Advances, was led by Andrew Tsourkas, Professor in Bioengineering and Co-Director of the Center for Targeted Therapeutics and Translational Nanomedicine (CT3N), who had what he describes as a “crazy idea” to use a patient’s antibodies to find and treat their own tumors, taking advantage of the immune system’s innate ability to identify tumors as foreign. This study, spearheaded by Burcin Altun, a former postdoctoral researcher in Tsourkas’s lab, and continued and completed by Fabiana Zappala, a former graduate student in Penn Bioengineering, details their new method for site-specifically labeling “off-the-shelf” and native serum autoantibodies with T cell–redirecting domains.

Researchers have known for some time that cancer patients will generate an antibody response to their own tumors. These anti-tumor antibodies are quite sophisticated in their ability to specifically identify cancer cells; however, they are not sufficiently potent to confer a therapeutic effect. In this study, Tsourkas’s team converted these antibodies into bispecific antibodies, thereby increasing their potency. T cell-redirecting bispecific antibodies are a new form of targeted therapeutic that forms a bridge between tumor cells and T cells which have been found to be as much as a thousand-times more potent than antibodies alone. By combining the specificity of a patient’s own antibodies with the potency of bispecific antibodies, researchers can effectively create a truly personalized therapeutic that is effective against tumors.

In order to test out this new targeted therapeutic approach, the Tsourkas lab had to develop an entirely new technology, allowing them to precisely label antibodies with T cell targeting domains, creating a highly homogeneous product.  Previously it has not been possible to convert native antibodies into bispecific antibodies, but Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine or TITAN lab specializes in the creation of novel targeted imaging and therapeutic agents for detection and treatment of various diseases. “Much is yet to be done before this could be considered a practical clinical approach,” says Tsourkas. “But I hope at the very least this works stimulates new ideas in the way we think about personalized medicine.”

In their next phase, Tsourkas’s team will be working to separate anti-tumor antibodies from other antibodies found in patients’ serum (which could potentially redirect the bispecific antibodies to other locations in the body), as well as examining possible adverse reactions or unintended effects and immunogenicity caused by the treatment. However, this study is just the beginning of a promising new targeted therapeutic approach to cancer treatment.

This work was supported by Emerson Collective and the National Institutes of Health, National Cancer Institute (R01 CA241661).

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Penn Anti-Cancer Engineering Center Will Delve Into the Disease’s Physical Fundamentals

by Evan Lerner

A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.

Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.

However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.

The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.

Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.

Dennis Discher and Ravi Radhakrishnan

The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.

Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.

Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).

Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).

Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.

Originally posted in Penn Engineering Today.

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‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’

William H. Peranteau, Michael J. Mitchell, Margaret Billingsley, Meghana Kashyap, and Rachel Riley (Clockwise from top left)

As COVID-19 vaccines roll out, the concept of using mRNA to fend off viruses has become a part of the public dialogue. However, scientists have been researching how mRNA can be used to in life-saving medical treatments well before the pandemic.

The “m” in “mRNA” is for “messenger.” A single-stranded counterpart to DNA, it translates the genetic code into the production of proteins, the building blocks of life. The Moderna and Pfizer COVID-19 vaccines work by introducing mRNA sequences that act as a set of instructions for the body to produce proteins that mimic parts of the virus itself. This prepares the body’s immune response to recognize the real virus and fight it off.

Because it can spur the production of proteins that the body can’t make on its own, mRNA therapies also have the potential to slow or prevent genetic diseases that develop before birth, such as cystic fibrosis and sickle-cell anemia.

However, because mRNA is a relatively unstable molecule that degrades quickly, it needs to be packaged in a way that maintains its integrity as its delivered to the cells of a developing fetus.

To solve this challenge, Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, is researching the use of lipid nanoparticles as packages that transport mRNA into the cell. He and William H. Peranteau, an attending surgeon in the Division of General, Thoracic and Fetal Surgery and the Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery at Children’s Hospital of Philadelphia, recently co-authored a “proof-of-concept” paper investigating this technique.

In this study, published in Science Advances, Mitchel examined which nanoparticles were optimal in the transport of mRNA to fetal mice. Although no disease or organ was targeted in this study, the ability to administer mRNA to a mouse while still in the womb was demonstrated, and the results are promising for the next stages of targeted disease prevention in humans.

Mitchel spoke with Tom Avril at The Philadelphia Inquirer about the mouse study and its implications for treatment of rare infant diseases through the use of mRNA, ‘the messenger of life.’

Penn bioengineering professor Michael J. Mitchell, the other senior author of the mouse study, tested various combinations of lipids to see which would work best.

The appeal of the fatty substances is that they are biocompatible. In the vaccines, for example, two of the four lipids used to make the delivery spheres are identical to lipids found in the membranes of human cells — including plain old cholesterol.

When injected, the spheres, called nanoparticles, are engulfed by the person’s cells and then deposit their cargo, the RNA molecules, inside. The cells respond by making the proteins, just as they make proteins by following the instructions in the person’s own RNA. (Important reminder: The RNA in the vaccines cannot become part of your DNA.)

Among the different lipid combinations that Mitchell and his lab members tested, some were better at delivering their cargo to specific organs, such as the liver and lungs, meaning they could be a good vehicle for treating disease in those tissues.

Continue reading Tom Avril’s ‘RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases?’ at The Philadelphia Inquirer.

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Bioengineering Faculty Contribute to New Treatment That “Halts Osteoarthritis-Like Knee Cartilage Degeneration”

A recent study published in Science Translational Medicine announces a discovery which could halt cartilage degeneration caused by osteoarthritis: “These researchers showed that they could target a specific protein pathway in mice, put it into overdrive and halt cartilage degeneration over time. Building on that finding, they were able to show that treating mice with surgery-induced knee cartilage degeneration through the same pathway via the state of the art of nanomedicine could dramatically reduce the cartilage degeneration and knee pain.” This development could eventually lead to treating osteoarthritis with injection rather than more complicated surgery.

Among a team of Penn Engineering and Penn Medicine researchers, the study was co-written by Zhiliang Cheng, Research Associate Professor in Bioengineering, Andrew Tsourkas, Professor in Bioengineering, and Ling Qin, Associate Professor of Orthopaedic Surgery in the Perelman School of Medicine and member of the Bioengineering Graduate Group. The lead author was Yulong Wei of the Department of Orthopaedic Surgery and the McKay Orthopaedic Research Laboratory.

Read the press release in Penn Medicine News.

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Christian Figueroa-Espada Named 2020-2021 Hispanic Scholarship Fund Scholar

Christian Figueroa-Espada

Christian Figueroa-Espada, a Penn Bioengineering Ph.D. student and National Science Foundation (NSF) Fellow, was selected as a Hispanic Scholarship Fund (HSF) Scholar from a highly-competitive pool of 85,000 applicants for their 2020-2021 program. One of only 5,100 awardees, Figueroa-Espada’s scholarship comes from the Toyota Motor North America Program. As an HSF Scholar, he has access to a full range of Scholar Support Services, such as career coaching, internship, and full-time employment opportunities, mentoring, leadership development, and wellness resources, including tools for self-advocacy, well-being, and knowledge building.

Born and raised in the Island of Enchantment, Puerto Rico, Figueroa-Espada received his B.S. in Mechanical Engineering from the University of Puerto Rico at Mayagüez, and is currently a second-year Ph.D. student in the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, where he is funded by the National Science Foundation Graduate Research Fellowship Program (NSF GRFP), the Graduate Education for Minorities (GEM) Fellowship Program, and the William Fontaine Fellowship. His research interests lie in the interface of biomaterials, drug delivery, and immunology – designing RNAi therapeutics for the reprogramming of the tumor microenvironment. His current project focuses on polymer-lipid drug delivery systems to study potential strategies to prevent homing and proliferation of multiple myeloma cancer within the bone marrow microenvironment. This project is part of the Mitchell lab’s recent National Institutes of Health (NIH) New Innovator Award.

“Chris has really hit the ground running on his Ph.D. studies at Penn Bioengineering, developing a new bone marrow-targeted nanoparticle platform to disrupt the spread of multiple myeloma throughout the body,” says Mitchell. “I’m very hopeful that this prestigious fellowship from HSF will permit him to make important contributions to nanomedicine and cancer research.”

Figueroa-Espada’s passion for giving back to his community has allowed him to be involved in many mentorship programs as part of his roles in the Society of Hispanics and Professional Engineers (SHPE), the National Society of Professional Engineers (NSPE), the Society of Women Engineers (SWE), and the Graduate Association of Bioengineers (GABE). He continues with his fervent commitment, now working with the Penn chapter of the Society for Advancement of Chicanos/Hispanics and Native Americans in Science (SACNAS), and the Penn Interdisciplinary Network for Scientists Promoting Inclusion, Retention, and Equity (INSPIRE) coalition where he plans on leading initiatives that aim to enhance diversity and student participation in science, especially students from historically marginalized groups.

“This fellowship, along with my NSF Graduate Research Fellowship, GEM Fellowship, and William Fontaine Fellowship through the University of Pennsylvania, make my research on nanoparticle-based RNA therapeutics for the reprogramming of the tumor microenvironment to treat malignancies and overcome drug resistance possible,” says Figueroa-Espada. “While my professional goal is to stay in academia and lead a research lab, my personal goal is to become whom I needed: a role model within the Latino STEM community, hoping to address many of the difficulties that impede Latino students’ success in higher education, and thanks to Toyota Motor/HSF, NSF, and GEM, I am one step closer to meeting these goals.”

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Penn Bioengineering’s Tsourkas Lab and Penn Start-up AlphaThera Awarded $667,000 SBIR Phase II Grant to Improve COVID-19 Detection Assays

To combat the COVID-19 pandemic caused by the SARS-CoV2 virus, Dr. Andrew Tsourkas’s Targeted Imaging Therapeutics and Nanomedicine (Titan) Lab in Penn Bioengineering, in collaboration with the Penn-based startup, AlphaThera, was recently awarded a $667,000 SBIR Phase II Grant Extension to support its efforts in commercializing COVID-19 detection technology. The grant supports work to address the growing need for anti-viral antibody testing. Specifically, the Tsourkas Lab and AlphaThera hope to leverage their expertise with antibody conjugation technologies to reduce the steps and complexity of existing detection assays to enable greater production and higher sensitivity tests. AlphaThera was founded in 2016 by Andrew Tsourkas, PhD, Professor of Bioengineering and James Hui, MD, PhD, a graduate of the Perelman School of Medicine and Penn Bioengineering’s doctoral program.

During this pandemic it is crucial to characterize disease prevalence among populations, understand immunity, test vaccine efficacy and monitor disease resurgence. Projections have indicated that millions of daily tests will be needed to effectively control the virus spread. One important testing method is the serological assay: These tests detect the presence of SARS-CoV2 antibodies in a person’s blood produced by the body’s immune system responding to infection. Serological tests not only diagnose active infections, but also establish prior infection in an individual, which can greatly aid in forecasting disease spread and contact tracing. To perform the serological assays for antibody detection, well-established immunoassay methods are used such as ELISA.

A variety of issues have slowed the distribution of these serological assays for antibody testing. The surge in demand for testing has caused shortages in materials and reagents that are crucial for the assays. Furthermore, complexity in some of the assay formats can slow both production and affect the sensitivity of test results. Recognizing these problems, AlphaThera is leveraging its novel conjugation technology to greatly improve upon traditional assay formats.

With AlphaThera’s conjugation technology, the orientation of antibodies can be precisely controlled so that they are aligned and uniformly immobilized on assay detection plates. This is crucial as traditional serological assays often bind antibodies to plates in a non-uniform manner, which increases variability of results and reduces sensitivity. See Fig 1 below. With AlphaThera’s uniform antibody immobilization, assay specificity could increase by as much as 1000- fold for detection of a patient’s SaRS-CoV2 antibodies.

Fig 1: Uniform vs Non-Uniform Immobilized Antibodies on Surface: Top is AlphaThera improvement, showing how antibodies would be uniformly immobilized and oriented on a plate for detection. Bottom is how many traditional serological assays immobilize antibodies, resulting in variability of results and lower specificity.

Furthermore, AlphaThera is addressing the shortage of assay reagents, specifically secondary antibody reagents, by removing certain steps from traditional serological assays. Rather than relying on secondary antibodies for detection of the patient antibodies, AlphaThera’s technology can label the patient SaRS-CoV2 primary antibodies directly in serum with a detection reagent. This eliminates several processing steps, reducing the time of the assay by as much as 50%, as well as the costs.

The Tsourkas Lab and AlphaThera have initiated their COVID-19 project, expanding into the Pennovation Center and onboarding new lab staff. Other antibody labeling products have also become available and are currently being prepared for commercialization. Check out the AlphaThera website to learn more about their technology at https://www.alphathera.com.

NIH SBIR Phase II Grant Extension— 5-R44-EB023750-03 (PI: Yu)  — 10/07/2020 – 10/07/2021