Tag: medicine

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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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With NIH Pioneer Award, Jennifer E. Phillips-Cremins Will Study Genome Folding’s Role in Long-term Memory

by Evan Lerner

Jennifer E. Phillips-Cremins (upper left) and members of her lab.

Each year, the National Institutes of Health (NIH) recognizes exceptionally creative scientists through its High-Risk, High-Reward Research Program. The four awards granted by this program are designed to support researchers whose “out of the box” and “trailblazing” ideas have the potential for broad impact.

Jennifer E. Phillips-Cremins, Associate Professor and Dean’s Faculty Fellow in Penn Engineering’s Department of Bioengineering and the Perelman School of Medicine’s Department of Genetics, is one such researcher. As a recipient of an NIH Director’s Pioneer Award, she will receive $3.5 million over five years to support her work on the role that the physical folding of chromatin plays in the encoding of neural circuit and synapse properties contributing to long-term memory.

Phillips-Cremins’ award is one of 106 grants made through the High-Risk, High-Reward program this year, though she is only one of 10 to receive the Pioneer Award, which is the program’s largest funding opportunity.

“The science put forward by this cohort is exceptionally novel and creative and is sure to push at the boundaries of what is known,” said NIH Director Francis S. Collins.

Phillips-Cremins’ research is in the general field of epigenetics, the molecular and structural modifications that allow the genome — an identical copy of which is found in each cell — to express genes differently at different times and in different parts of the body. Within this field, her lab focuses on higher-order folding patterns of the DNA sequence, which bring distant sets of genes and regulatory elements into close proximity with one another as they are compressed inside the cell’s nucleus.

Previous work from the Cremins lab has investigated severe genome misfolding patterns common across a class of genetic neurological disorders, including fragile X syndrome, Huntington’s disease, ALS and Friedreich’s ataxia.

With the support of the Pioneer Award, she and the members of her lab will extend that research to a more fundamental question of neuroscience: how memory is encoded over decades, despite the rapid turnover of the relevant proteins and RNA sequences within the brain’s synapses.

“Our long-term goals are to understand how, when and why pathologic genome misfolding leads to synaptic dysfunction by way of disrupted gene expression,” said Phillips-Cremins, “as well as to engineer the genome’s structure-function relationship to reverse pathologic synaptic defects in debilitating neurological diseases.”

Originally posted in Penn Engineering Today.

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Penn Establishes the Center for Precision Engineering for Health with $100 Million Commitment

by Evan Lerner

The Center for Precision Engineering for Health will bring together researchers spanning multiple scientific fields to develop novel therapeutic biomaterials, such as a drug-delivering nanoparticles that can be designed to adhere to only to the tissues they target. (Image: Courtesy of the Mitchell Lab)

The University of Pennsylvania announced today that it has made a $100 million commitment in its School of Engineering and Applied Science to establish the Center for Precision Engineering for Health.

The Center will conduct interdisciplinary, fundamental, and translational research in the synthesis of novel biomolecules and new polymers to develop innovative approaches to design complex three dimensional structures from these new materials to sense, understand, and direct biological function.

“Biomaterials represent the ‘stealth technology’ which will create breakthroughs in improving health care and saving lives,” says Penn President Amy Gutmann. “Innovation that combines precision engineering and design with a fundamental understanding of cell behavior has the potential to have an extraordinary impact in medicine and on society. Penn is already well established as an international leader in innovative health care and engineering, and this new Center will generate even more progress to benefit people worldwide.”

Penn Engineering will hire five new President’s Penn Compact Distinguished Professors, as well as five additional junior faculty with fully funded faculty positions that are central to the Center’s mission. New state-of-the-art labs will provide the infrastructure for the research. The Center will seed grants for early-stage projects to foster advances in interdisciplinary research across engineering and medicine that can then be parlayed into competitive grant proposals.

“Engineering solutions to problems within human health is one of the grand challenges of the discipline,” says Vijay Kumar, Nemirovsky Family Dean of Penn Engineering. “Our faculty are already leading the charge against these challenges, and the Center will take them to new heights.”

This investment represents a turning point in Penn’s ability to bring creative, bio-inspired approaches to engineer novel behaviors at the molecular, cellular, and tissue levels, using biotic and abiotic matter to improve the understanding of the human body and to develop new therapeutics and clinical breakthroughs. It will catalyze integrated approaches to the modeling and computational design of building blocks of peptides, proteins, and polymers; the synthesis, processing, and fabrication of novel materials; and the experimental characterizations that are needed to refine approaches to design, processing, and synthesis.

“This exciting new initiative,” says Interim Provost Beth Winkelstein, “brings together the essential work of Penn Engineering with fields across our campus, especially in the Perelman School of Medicine. It positions Penn for global leadership at the convergence of materials science and biomedical engineering with innovative new techniques of simulation, synthesis, assembly, and experimentation.”

Examples of the types of work being done in this field include new nanoparticle technologies to improve storage and distribution of vaccines, such as the COVID-19 mRNA vaccines; the development of protocells, which are synthetic cells that can be engineered to do a variety of tasks, including adhering to surfaces or releasing drugs; and vesicle based liquid biopsy for diagnosing cancer.

N.B.: This story originally appeared in Penn Engineering Today.

Beth Winkelstein is the Eduardo D. Glandt President’s Distinguished Professor in Bioengineering.

The featured illustration comes from a recent study led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering, and Margaret Billingsley, a graduate student in his lab.

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BE Seminar: “Material Design for Lymph Node Drug Delivery and Immunomodulation” (Susan Thomas)

Susan Thomas, Ph.D.

Speaker: Susan N. Thomas, Ph.D.
Woodruff Associate Professor of Mechanical Engineering
Parker H. Petit Institute of Bioengineering and Bioscience
Georgia Institute of Technology

Date: Thursday, September 23, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
This virtual seminar will be held over Zoom. Students registered for BE 699 can gather to watch live in Moore 216, 200 S. 33rd Street.

Abstract: Lymph nodes mediate the co-mingling of cells of the adaptive system to coordinate adaptive immune response. Drug delivery principles and technologies our group has developed to leverage the potential of lymph nodes as immunotherapeutic drug targets to augment anti-cancer therapeutic effects will be described.

Susan Thomas Bio: Susan Napier Thomas is a Woodruff Associate Professor with tenure of Mechanical Engineering in the Parker H. Petit Institute of Bioengineering and Bioscience at the Georgia Institute of Technology where she holds adjunct appointments in Biomedical Engineering and Biological Science and is a member of the Winship Cancer Institute of Emory University. Prior to this appointment, she was a Whitaker postdoctoral scholar at École Polytechnique Fédérale de Lausanne and received her B.S. in Chemical Engineering cum laude from the University of California Los Angeles and her Ph.D. as in Chemical & Biomolecular Engineering as an NSF Graduate Research Fellow from The Johns Hopkins University. For her contributions to the emerging field of immunoengineering, she has been honored with the 2018 Young Investigator Award from the Society for Biomaterials for “outstanding achievements in the field of biomaterials research” and the 2013 Rita Schaffer Young Investigator Award from the Biomedical Engineering Society “in recognition of high level of originality and ingenuity in a scientific work in biomedical engineering.” Her interdisciplinary research program is supported by multiple awards from the National Cancer Institute, the Department of Defense, the National Science Foundation, and the Susan G. Komen Foundation, amongst others.

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Developing New Technologies to Solve the Mysteries of the Brain

Flavia Vitale, assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founder of the multidisciplinary Vitale Lab. (Image: Penn Medicine News)

Neurology, bioengineering, and physical medicine and rehabilitation might not seem like three disciplines that fit together, but for Flavia Vitale, an assistant professor of all three, it makes perfect sense. As the director and principal investigator at the Vitale Lab, her research focuses on developing new technologies that help to study how the brain and neuromuscular systems function.

Years ago, while she was working at Rice University developing new materials and devices that work in the body in a safer, more effective way, former president Barack Obama launched the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, aimed at revolutionizing the understanding of the human brain. This emphasis on how little is known about brain structure and function inspired Vitale to refocus her research on developing technology and materials that will help researchers solve the mysteries of the brain.

In 2018, she joined the faculty at the Perelman School of Medicine as an assistant professor of neurology, bioengineering, and physical medicine and rehabilitation, and founded the multidisciplinary Vitale Lab, where her team develops cutting edge materials and devices that will someday help clinicians diagnose and treat patients with complicated brain and neurological conditions. She is also one of the engineers looking forward to using new combined clinical/research facilities in neuroscience at Penn Medicine’s new Pavilion where new neurotechnoloigies will be developed and tested.

“My main goal is to create tools that can help solve mysteries of the brain, and address the needs of clinicians,” she says.

“My lab was recently awarded two grants totaling $4.5 million from the National Institute of Neurological Disorders and Stroke. In order to obtain more precise insights, noninvasively, into brain activity to improve gene therapy treatments for a range of diagnoses, from Parkinson’s disease to glioblastoma. The first grant is designated for the development of a novel surgical device for delivering gene-based therapeutics to the brain. The second is for optimization and pre-clinical validation of a novel EEG electrode technology, which uses a soft, flexible, conductive nanomaterial rather than metal and gels. We hope to confirm that these technologies work as well as, if not better than existing ones.”

Read the full story in Penn Medicine News.

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BE Seminar: “Dynamics of 3D Cell Migration and Organ Formation” (Kenneth Yamada)

Our next Penn Bioengineering seminar will be held on zoom next Thursday.

Kenneth Yamada, MD, PhD

Speaker: Kenneth Yamada, M.D., Ph.D.
NIH Distinguished Investigator
Cell Biology Section
National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH)

Date: Thursday, September 9, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: Real-time microscopy of the dynamics of cells and tissues in 3D environments is opening new windows to understanding the biophysical mechanisms of complex biological processes. Direct visualization is allowing us to explore fundamental questions in more depth that include: How do cells migrate in 3D? How do cancer cells invade? How is the extracellular matrix assembled? How are organs formed? Visualizing how cells move and organize into tissues is not only providing descriptive insights, but is also leading to the identification of novel, unexpected physical and mechanical mechanisms relevant to tissue engineering. Cells can use varying combinations of cell adhesion to adjacent cells and to the surrounding extracellular matrix with localized cellular contractility to migrate, invade, and produce the complex tissue architecture needed for organ formation.

Kenneth Yamada Bio: Kenneth Yamada has been an NIH Distinguished Investigator since 2011. He received MD and PhD degrees from Stanford. He was a Section Chief at the National Cancer Institute for 10 years and has been a Section Chief at NIDCR since 1990. He is an elected Fellow of the AAAS and American Society for Cell Biology. His research focuses on discovering novel mechanisms and regulators of cell interactions with the extracellular matrix and their roles in embryonic development and cancer. His research group focuses on the mechanisms by which three-dimensional (3D) extracellular matrix mediates key biological events, including cell migration, tissue morphogenesis, and cancer cell invasion. His research places particular emphasis on characterizing the dynamic movements of cells and their extracellular matrix as tissues are remodeled in 3D in real time. The biological systems they study include human primary cells migrating in 3D, human tumor cells and tissues, and mouse organ development. He places particularly high priority on developing future independent research leaders.

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BE Seminar: “Synthetic Biochemistry: Engineering Molecules and Pathways for Precision Medicine” (Michael Lin)

Save the date for the first Penn Bioengineering seminar of the fall 2021 semester! This year’s seminars will be hybrids, held virtually on zoom and live on campus!

Michael Lin, Ph.D.

Speaker: Michael Lin, Ph.D.
Associate Professor
Neurobiology, Bioengineering, and by courtesy Chemical and Systems Biology
Stanford Medicine, Stanford University

Date: Thursday, September 2, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Location: Moore Room 216, 200 S. 33rd Street

Abstract: The most effective medicines are those that target the earliest causes of disease, rather than later manifestations. Engineering of biomolecules is a promising but underexplored approach to precisely detecting or targeting disease causes. I will present our work to develop a novel approach to treating cancer by detecting the signaling abnormalities that give rise to cancer. Interestingly, this effort involves biomolecular engineering at multiple scales: proteins, pathways, and viruses. I will also discuss how our work has translated serenditously to developing treatments for SARSCoV2.

Michael Lin Bio: Michael Z. Lin received an A.B. summa cum laude in Biochemistry from Harvard, an M.D. from UCLA, and a Ph.D. from Harvard Medical School. After training in biochemistry and neurobiology as a PhD student with Michael Greenberg at Harvard Medical School, Dr. Lin performed postdoctoral research in fluorescent protein engineering with Chemistry Nobel Laureate Roger Y. Tsien at UCSD. Dr. Lin is a recipient of a Burroughs Wellcome Career Award for Medical Scientists, a Rita Allen Scholar Award, a Damon Runyon-Rachleff Innovation Award, and a NIH Pioneer Award.

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Penn Bioengineering Senior Design Team Wins Hamlyn Symposium Prize

The winners of the Medical Robots for Contagious Disease Challenge Award for Best Application (L to R): Yasmina Al Ghadban, Phuong Vu, and Rob Paslaski.

Three recent Penn Bioengineering graduates took home the Best Application Award from the Medical Robotics for Contagious Disease Challenge, part of the three-month Hamlyn Symposium on Medical Robotics. Organized by the Hamlyn Centre at Imperial College, London, UK, in collaboration with the UK-RAS Network, the challenge involved “creating a 2-minute video of robotic or AI technology that could be used to tackle contagious diseases” in response to the current and potential future pandemics. Yasmina Al Ghadban, Rob Paslaski, and Phuong Vu were members of the Penn Bioengineering senior design team rUmVa who designed and built a cost-effective, autonomous robot that can quickly disinfect rooms by intelligently sanitizing high-touch surfaces and the air. The Best Application Award comes with a prize of £5,000.

The full Team rUmVa (L to R): Yasmina Al Ghadban, Rachel Madhogarhia, Phuong Vu, Jeong Inn Park, and Rob Paslaski.

Team rUmVa, which also included Bioengineering seniors Rachel Madhogarhia and Jeong Inn Park, also received a Berkman Opportunity fund grant from Penn Engineering and was one of three teams to win Penn Bioengineering’s Senior Design competition. Senior Design work is conducted every year on-site in the George H. Stephenson Foundation Educational Laboratory & Bio-MakerSpace (which successfully reopened for in-person activities this Spring semester). Read the full list of Spring 2021 Senior Design Award Winners here.

rUmVa and the other challenge winners were honored during the Hamlyn Symposium’s virtual closing ceremony on July 29, 2021.

Read rUmVa’s abstract and final papers, along with those of all of the Penn Bioengineering Teams’, on the BE Labs Senior Design 2021 website. rUmVa’s presentation can be viewed on Youtube:

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Penn Bioengineering Graduate Shreya Parchure Receives Rose Award

Shreya Parchure (BSE/MSE 2021)

Shreya Parchure, a recent graduate of Penn Bioengineering, was selected by a committee of faculty for a 2021 Rose Award from the Center for Undergraduate Research and Fellowships (CURF). The Rose Award recognizes outstanding undergraduate research projects completed by graduating seniors under the supervision of a Penn faculty member and carries with it a $1,000 award. Parchure’s project, titled “BDNF Gene Polymorphism Predicts Response to Continuous Theta Burst Stimulation (cTBS) in Chronic Stroke Patients,” was done under the supervision of Roy H. Hamilton, Associate Professor in Neurology and Physical Medicine and Rehabilitation and director of the Laboratory for Cognition and Neural Stimulation in the Perelman School of Medicine. Parchure’s work in Hamilton’s lab previously resulted in a 2020 Goldwater Scholarship.

Parchure graduated in Spring 2021 with a B.S.E. in Bioengineering, with concentrations in Neuroengineering and Medical Devices and a minor in Chemistry, as well as a M.S.E. in Bioengineering. During her time as an undergraduate, she was a Rachleff Scholar, a recipient of a Vagelos Undergraduate Research Grant, and the Wolf-Hallac Award. She was active in many groups across the university and beyond, serving as a United Nations Millennium Fellow, a volunteer with Service Link and the Hospital of the University of Pennsylvania (HUP), a CURF Research Peer Advisor, and co-editor-in-chief of the Penn Bioethics Journal. She is now pursuing a M.D./Ph.D. through the Medical Scientist Training Program at Penn Bioengineering and the Perelman School of Medicine.

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With a ‘Liquid Assembly Line,’ Penn Researchers Produce mRNA-Delivering-Nanoparticles a Hundred Times Faster than Standard Microfluidic Technologies

by Evan Lerner

Michael Mitchell, Sarah Shepherd and David Issadore pose with their new device.

The COVID vaccines currently being deployed were developed with unprecedented speed, but the mRNA technology at work in some of them is an equally impressive success story. Because any desired mRNA sequence can be synthesized in massive quantities, one of the biggest hurdles in a variety of mRNA therapies is the ability to package those sequences into the lipid nanoparticles that deliver them into cells.

Now, thanks to manufacturing technology developed by bioengineers and medical researchers at the University of Pennsylvania, a hundred-fold increase in current microfluidic production rates may soon be possible.

The researchers’ advance stems from their design of a proof-of-concept microfluidic device containing 128 mixing channels working in parallel. The channels mix a precise amount of lipid and mRNA, essentially crafting individual lipid nanoparticles on a miniaturized assembly line.

This increased speed may not be the only benefit; more precisely controlling the nanoparticles’ size could make treatments more effective. The researchers tested the lipid nanoparticles produced by their device in a mouse study, showing they could deliver therapeutic RNA sequences with four-to-five times greater activity than those made by conventional methods.

The study was led by Michael Mitchell, Skirkanich Assistant Professor of Innovation in Penn Engineering’s Department of Bioengineering, and David Issadore, Associate Professor in Penn Engineering’s Department of Bioengineering, along with Sarah Shepherd, a doctoral student in both of their labs. Rakan El-Mayta, a research engineer in Mitchell’s lab, and Sagar Yadavali, a postdoctoral researcher in Issadore’s lab, also contributed to the study.

They collaborated with several researchers at Penn’s Perelman School of Medicine: postdoctoral researcher Mohamad-Gabriel Alameh, Lili Wang, Research Associate Professor of Medicine, James M. Wilson, Rose H. Weiss Orphan Disease Center Director’s Professor in the Department of Medicine, Claude Warzecha, a senior research investigator in Wilson’s lab, and Drew Weissman, Professor of Medicine and one of the original developers of the technology behind mRNA vaccines.

It was published in the journal Nano Letters.

“We believe that this microfluidic technology has the potential to not only play a key role in the formulation of current COVID vaccines,” says Mitchell, “but also to potentially address the immense need ahead of us as mRNA technology expands into additional classes of therapeutics.”

Read the full story in Penn Engineering Today.