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.

Engineering Entrepreneurship with Professor Thomas Cassel

Thomas A.V. Cassel, Practice Professor in Mechanical Engineering and Applied Mechanics in the School of Engineering and Applied Science, recently sat down with Dayo Adetu (BSE 2019, MSE 2021), President of the Penn Graduate Association of Bioengineers (GABE), to give his insight into engineering entrepreneurship. Cassel is the Director of Penn’s Engineering Entrepreneurship Program, which he founded twenty one years ago. He joined Penn’s faculty in 1999 following a 20-year career of entrepreneurial business leadership.

Watch the video to hear about Cassel’s favorite Penn memories, the day-to-day experience of working at a startup, advice for venturing into entrepreneurship, and more.

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.

Penn Engineers Will Use NSF Grant to Develop ‘DReAM’ for On-demand, On-site mRNA Manufacturing

by Melissa Pappas

Daeyeon Lee, Kathleen Stebe and Michael Mitchell

COVID-19 vaccines are just the beginning for mRNA-based therapies; enabling a patient’s body to make almost any given protein could revolutionize care for other viruses, like HIV, as well as various cancers and genetic disorders. However, because mRNA molecules are very fragile, they require extremely low temperatures for storage and transportation. The logistical challenges and expense of maintaining these temperatures must be overcome before mRNA therapies can become truly widespread.

With these challenges in mind, Penn Engineering researchers are developing a new manufacturing technique that would be able to produce mRNA sequences on demand and on-site, isolating them in a way that removes the need for cryogenic temperatures. With more labs able to make and store mRNA-based therapeutics on their own, the “cold chain” between manufacturer and patient can be made shorter, faster and less expensive.

The National Science Foundation (NSF) is supporting this project, known as Distributed Ribonucleic Acid Manufacturing, or DReAM, through a four-year, $2 million grant from its Emerging Frontiers in Research and Innovation (EFRI) program.

The project will be led by Daeyeon Lee, Evan C Thompson Term Chair for Excellence in Teaching and Professor in the Department of Chemical and Biomolecular Engineering (CBE), along with Kathleen Stebe, Richer and Elizabeth Goodwin Professor in CBE and in the Department of Mechanical Engineering and Applied Mechanics. They will collaborate with Michael Mitchell, Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, Drexel University’s Masoud Soroush and Michael Grady, the University of Oklahoma’s Dimitrios Papavassiliou and the University of Colorado Boulder’s Joel Kaar.

Read the full story in Penn Engineering Today.

Bioengineering Graduate Dayo Adetu Wins Graduate Leadership Award

Dayo Adetu (BSE 2019, MSE 2021)

Congratulations to recent Penn Bioengineering graduate Dayo Adetu, who was awarded a 2021 Graduate Leadership Award, one of only sixteen recipients across the university. Adetu is a recipient of the Dr. Andy Binns Award for Outstanding Service to Graduate and Professional Student Life. This award is presented to “graduate or professional students, upon their graduation from Penn, who have significantly impacted graduate and professional student life through service involvement in student life initiatives or organizations.” Adetu wins this award for her “service and leadership in advancing wellness and diversity initiatives across departments in the School of Engineering.”

Adetu graduated with a BSE in Bioengineering (BE) in 2019, concentrating in Biomedical Devices and minoring in Engineering Entrepreneurship, Math, and African Studies. She went on to pursue two Master’s degrees in BE and Mechanical Engineering and Applied Mechanics (MEAM) (concentration: Design and Manufacturing), graduating with both in 2021. She also received a certificate in Integrated Product Design. For the 2020-2021 academic year, she served as President of the Penn chapters of both the Graduate Association of Bioengineers (GABE) and the Mechanical Engineering Graduate Association (MEGA). She was the 2021 MEAM MSE Graduation student speaker and also received the Penn Engineering Graduate Award for Outstanding Service for both BE and MEAM Departments.

Learn more about the Penn Graduate Leadership Awards and read the full list of recipients on the Grad Center at Penn website.

BE Seminar: “Engineering Synthetic Biomaterials for Islet Transplantation” (María M. Coronel)

Speaker: María M. Coronel, Ph.D.
Postdoctoral Fellow, the George W. Woodruff School of Mechanical Engineering
Georgia Institute of Technology

Date: Thursday, February 18, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Engineering Synthetic Biomaterials for Islet Transplantation”

Abstract:

Two major challenges to the translation of cellular-based tissue-engineered therapies are the lack of adequate oxygen support post-implantation and the need for systemic immunosuppression to halt the strong inflammatory and immunological response of the host. As such, strategies that aim at addressing oxygen demand, and local immunological responses can be highly beneficial in the translation of these therapies. In this seminar, I will focus on two biomaterial strategies to create a more favorable transplant niche for pancreatic islet transplantation. The first half will describe an in-situ oxygen-releasing biomaterial fabricated through the incorporation of solid peroxides in a silicone polymer. The implementation of this localized, controlled and sustained oxygen-generator mitigates the activation of detrimental hypoxia-induced pathways in islets and enhances the potency of extrahepatic 3D islet-loaded devices in a diabetic animal model. In the second part, I will focus on engineering synthetic biomaterials for the delivery of immunomodulatory signals for transplant acceptance. Biomaterial carriers fabricated with polyethylene glycol microgels are used to deliver immunomodulatory signals to regulate the local microenvironment and prevent allograft rejection in a clinically relevant pre-clinical transplant model. The use of synthetic materials as an off-the-shelf platform, without the need for manipulating the biological cell product, improves the clinical translatability of this engineered approach. Designing safer, responsive biomaterials to boost the delivery of targeted therapeutics will significantly reinvigorate interventional cell-based tissue-engineered therapies.

Bio:

Dr. María M. Coronel is currently a Juvenile Diabetes Research Foundation postdoctoral fellow at the Georgia Institute of Technology. Dr. Coronel completed her BS degree in Biomedical Engineering from the University of Miami, and her Ph.D. degree in Biomedical Engineering from the University of Florida as a National Institute of Health predoctoral fellow. Her doctoral work focused on engineering oxygen-generating materials for addressing the universal challenge of hypoxia within three-dimensional tissue-engineered implants. As a postdoctoral fellow, her research interest focus on engineering tools and principles to understand, stimulate, and modulate the immune system to develop controlled targeted interventional therapies. In addition to research, Dr. Coronel aims to be an advocate for diversity and inclusion in STEM as the co-president of the postdoctoral group and a founding member of the diversity, equity, and inclusion committee in bioengineering at Georgia Tech. Outside of the lab María enjoys cooking, baking, and traveling.

BE/MEAM Seminar: “Microbes in Biomechanics” (Christopher J. Hernandez)

Speaker: Christopher J. Hernandez, Ph.D.
Professor, Sibley School of Mechanical and Aerospace Engineering, Cornell University
Adjunct Scientist, Hospital for Special Surgery

Date: Thursday, February 4, 2021
Time: 3:00-4:00 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu

Title: “Microbes in Biomechanics”

This seminar is jointly hosted by the Department of Bioengineering and the Department of Mechanical Engineering and Applied Mechanics.

Abstract:

The idea that mechanical stresses influence the growth and form of organs and organisms originated in the 1800s and is the basis for the modern study of biomechanics and mechanobiology. Biomechanics and mechanobiology are well studied in eukaryotic systems, yet eukaryotes represent only a small portion of the diversity and abundance of life on Earth. Bacteria exhibit broad influences on human health (as both pathogens and as beneficial components of the gut microbiome) and processes used in biotechnology and synthetic biology. Over the past eight years my group has explored mechanobiology within individual bacteria and the effects of changes in the composition of commensal bacterial communities on the biomechanics in the musculoskeletal system.

The ability of the bacteria to not only resist mechanical loads (biomechanics) but also to respond to changes in the mechanical environment (mechanobiology) is necessary for survival. Here I describe a novel microfluidic platform used to explore the biomechanics and mechanobiology of individual, live bacteria. I discuss work from my group demonstrating that mechanical stress within the bacterial cell envelope can influence the assembly and function of multicomponent efflux pumps used by bacteria to resist toxins and antibiotics. Additionally, I share some of our more recent work showing that mechanical stress and strain within the bacterial cell envelope can stimulate a bacterial two-component system controlling gene expression. Our findings demonstrate that bacteria, like mammalian cells, have mechanosensitive systems that are key to survival.

In musculoskeletal disease, bacteria are commonly viewed as sources of infection. However, in the past decade the studies by my group and others have suggested that commensal bacteria – the microbiome – can modulate the pathogenesis of musculoskeletal disorders. My group is among the first to study the effects of the gut microbiome on orthopaedic disorders. Here I provide an introduction to the microbiome and current concepts of how modifications to the gut microbiome could influence the musculoskeletal system. Specifically, I discuss studies from my group which are the first to demonstrate that the gut microbiome influences bone biomechanics and the development of infection of orthopaedic implants.

Bio:

Dr. Hernandez is Professor in the Sibley School of Mechanical and Aerospace Engineering at Cornell University and is an Adjunct Scientist at the Hospital for Special Surgery. Dr. Hernandez is a Fellow of the American Institute for Medical and Biological Engineering (AIMBE), the American Society of Mechanical Engineers (ASME), and the American Society for Bone and Mineral Research (ASBMR). He is the 2018 recipient of the Fuller Albright Award for Scientific Excellence from the American Society for Bone and Mineral Research. He has served on the Board of Directors of the Orthopaedic Research Society and the American Society for Bone and Mineral Research. His laboratory’s research currently focuses on the effects of the microbiome on bone and joint disorders, periprosthetic joint infection and the biomechanics and mechanobiology of bacteria.

hernandezresearch.com

Melanie Hilman Finds Community in Bioengineering

Penn Bioengineering senior and MEAM submatriculant, Melanie Hilman

Melanie Hilman was born to be a Biomedical Engineer. The daughter of an electrical engineering father and physician mother, Melanie was inspired by her parents work and is now pursuing the intersection of their two careers: bioengineering.

LIFELONG LEARNER

Her passion for engineering began long before Melanie stepped onto Smith Walk.

“I always really loved math and science as a middle school and high school student,” Melanie says.

Melanie quickly discovered that Penn was the perfect place for her. After visiting campus as a prospective student, Melanie knew that she wanted to attend a research-driven university where innovation and discovery was at the top of the curriculum.

“Being in a place so rich with research and really smart minds motivated me to apply here and be a part of this program,” Melanie remembers.

On top of her bioengineering research, Melanie submatriculated into Mechanical Engineering and Applied Mechanics with a focus on Mechanics of Materials because she wants to develop a deep foundation in the mathematical concepts. After gaining this experience, Melanie hopes to conduct complex research and eventually pursue a PhD.

BETWEEN TWO WORLDS

“I really like thinking about the interface between biology and today’s technologies,” Melanie comments. Right now, she’s focused on doing research but she is interested in, one day, developing biomedical technologies for the start-up industry.

As if building the future of bioengineering weren’t enough for Melanie, she is a dedicated member of the Penn community outside of the lab. Throughout her time at Penn, Melanie is a student leader of Penn Hillel, a devoted performer in the Penn Symphony Orchestra and Penn Chamber Music, and a multimedia staff member of the Daily Pennsylvanian. Even when school is out of session, Melanie represents Penn during Alternative Spring Break trips where she took on a leadership position renovating houses in West Virginia. All of this extracurricular work is important to Melanie, as she says these experiences have given her a valuable perspective to carry with her through academic, professional and personal life.

“It makes me feel really fortunate for my upbringing and my experiences,” Melanie shares.

Melanie performs at a concert with Penn Symphony Orchestra

WOMEN IN STEM

When asked about her favorite part of being at Penn Engineering, Melanie was certain about her answer: empowered women engineers.

“Having a really strong female engineering network is super valuable to me,” Melanie says.

Melanie says she’s found friendship and support among her fellow women engineers and that working with women is as fun as it is enriching. While Penn Engineering has proved itself to be an inclusive space for Melanie and others, current research shows that only 13% of professional engineers are women, and, among them, biomedical engineering ranks fourth in terms of career path of women engineers. Faced with these jarring numbers, Melanie is even more committed to encouraging other women to join her in STEM.

Most of all, she is grateful for the community she has found on campus.

“I know I’m going to have a good group of friends after I graduate. I have found other women that I hope to have lasting friendships with.”

Armed with friends and research partners, Melanie Hillman may very well turn the tides for women in engineering and usher in a new era of women in the lab who lead the charge for biomedical innovation.

Originally posted on the Penn Engineering blog.

BE Seminar Series: November 21st with Sumita Pennathur, Ph.D.

Sumita Pennathur, Ph.D.

Speaker: Sumita Pennathur, Ph.D.
Professor of Mechanical Engineering
University of California, Santa Barbara

Date: Thursday, November 21, 2019
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Nanofluidic Technologies for Biomolecule Manipulation”

Abstract:

In the last 20 years, microfabrication techniques have allowed researchers to miniaturize tools for a plethora of bioanalytical applications.  In addition to better sensitivity, accuracy and precision, scaling down the size of bioanalytical tools has led to the exploitation of new technologies to further manipulate biomolecules in ways that has never before been achieved. For example, when microfluidic channels are on the same order of magnitude of the electric double layers that form due to localized charge at the surfaces, there exists unique physics that create different flow phenomenon, such as analyte concentration and/or separation, mainly due to the couples physics of electrostatics and fluid dynamics. This talk will outline the basis of such interesting phenomena, such as nanofluidic  separation and concentration, and well as probe the applications of such coupled systems, for example, handheld DNA detection. Most importantly, we will focus on the most recent work in the Pennathur lab in this field —  biopolar electrode (BPE)-based phenomenon. Bipolar electrodes (BPE) have been studied in microfluidic systems over the past few decades, and through rigorous experimentally-validated modeling of the rich combined physics of fluid dynamics, electrokinetics, and electrochemistry at BPEs, I will show the potential of utilizing microfluidic-based BPEs for the design and development of low power, accurate, low volume fluid pumping mechanisms, with the ultimate goal of integration into wearable drug delivery and µTAS systems.

Bio:

Professor Pennathur has been a Professor of Mechanical Engineering at University of California, Santa Barbara in 2007, specializing in the fields of MEMS, nanofludics, and electrokinetics.  Her most significant contributions include: 1) unearthing a novel mechanism for separation and concentration of analytes for bioanalytical applications, 2) developing a label-free detection mechanism for nucleic acids (that has since spun off into a point-of-care diagnostic company), 3) developing commercial medical diagnostic products, 4) building optical and acoustic biosensors and 5) developing revolutionized methods for measuring blood glucose for patients with diabetes. She received her B.S. and M.S. from MIT and PhD. From Stanford University.