Earlier this year, Penn President Amy Gutmann and Vijay Kumar, Nemirovsky Family Dean of Penn’s School of Engineering and Applied Science, announced a $100 million commitment to accelerate innovations in medical technologies. Called the Center for Precision Engineering for Health (CPE4H), the initiative aims to bring together researchers from a wide range of fields to develop customizable biomaterials and implantable devices that can be tailored for individualized diagnostics, treatments and therapies.
Now, Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Penn Engineering’s Departments of Bioengineering and Chemical and Biomolecular Engineering, has been named CPE4H’s inaugural director.
“Penn is a unique environment where innovations in healthcare can emerge very rapidly, as we’ve seen with the development of CAR-T cancer immunotherapy, and the design and delivery of mRNA vaccines,” Hammer says. “Engineering plays a central role in making those technologies functional and maximizing their impact, and CPE4H is a golden opportunity to take these technologies to the next level in a way that actually helps people.”
The impending danger of bacterial resistance to antibiotics is well-documented within the scientific community. Bacteria are the most efficient evolvers, and their ability to develop tolerance to drugs, in addition to antibiotic overuse and misuse, means that researchers have had to get particularly resourceful to ensure the future of modern medicine.
WIRED’s Max G. Levy recently spoke with de la Fuente and postdoctoral researcher and study collaborator Marcelo Torres about the urgency of the team’s work, and why developing these solutions is critical to the survival of civilization as we know it. The team’s algorithm, based on pattern recognition software used to analyze images, makes an otherwise insurmountable feat tangible.
De la Fuente’s lab specializes in using AI to discover and design new drugs. Rather than making some all-new peptide molecules that fit the bill, they hypothesized that an algorithm could use machine learning to winnow down the huge repository of natural peptide sequences in the human proteome into a select few candidates.
“We know those patterns—the multiple patterns—that we’re looking for,” says de la Fuente. “So that allows us to use the algorithm as a search function.”
Speaker: Shelly R. Peyton, Ph.D.
Professor, Armstrong Professional Development Professor
Chemical Engineering, Biomedical Engineering Adjunct
College of Engineering
University of Massachusetts Amherst
Date: Thursday, December 9, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link
This seminar will be held virtually, but students registered for BE 699 can gather to watch in Moore 216.
Abstract: Improved experimental model systems are critically needed to better understand cancer progression and bridge the gap between lab bench proof-of-concept studies, validation in animal models, and eventual clinical application. Many methods exist to create biomaterials, including hydrogels, which we use to study cells in contexts more akin to what they experience in the human body. Our lab has multiple approaches to create such biomaterials, based on combinations of poly(ethylene glycol) (PEG) with peptides and zwitterions. In this presentation, I will discuss our synthetic approaches to building life-like materials, how we use these systems to grow cells and understand how a cell’s environment, particularly the extracellular matrix regulates cancer cell growth, dormancy, and drug sensitivity.
Shelly Peyton Bio: Shelly Peyton is the Armstrong Professor and Graduate Program Director, and chair of the Diversity, Equity, and Inclusion (DEI) committee of Chemical Engineering at the University of Massachusetts Amherst. She is co-director of the Models 2 Medicine Center in the Institute for Applied Life Sciences. She received her B.S. in Chemical Engineering from Northwestern University in 2002 and went on to obtain her MS and PhD in Chemical Engineering from the University of California, Irvine. She was then an NIH Kirschstein post-doctoral fellow in the Biological Engineering department at MIT before starting her academic appointment at UMass in 2011. Shelly leads an interdisciplinary group of engineers and molecular cell biologists seeking to create and apply novel biomaterials platforms toward new solutions to grand challenges in human health. Her lab’s unique approach is using our engineering expertise to build simplified models of human tissue with synthetic biomaterials. They use these systems to understand 1) the physical relationship between metastatic breast cancer cells and the tissues to which they spread, 2) the role of matrix remodeling in drug resistance, and 3) how to create bioinspired mechanically dynamic and activatable biomaterials. Among other honors for her work, Shelly was a 2013 Pew Biomedical Scholar, received a New Innovator Award from the NIH, and she was awarded a CAREER grant from the NSF. Shelly is co-PI with Jeanne Hardy on the Biotechnology (BTP) NIH T32 program and is a co-PI of the PREP program at UMass, which brings students from URM groups to UMass for a 1-year post-BS study to help prepare them for graduate school.
Speaker: Samir Mitragotri, Ph.D.
Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering
John A. Paulson School of Engineering and Applied Sciences
Harvard University
Date: Thursday, November 18, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link or contact ksas@seas.upenn.edu
This seminar will be held virtually, but students registered for BE 699 can gather to watch in Moore 216.
Abstract: Ionic liquids, the liquid salts comprising organic anions and cations, offer exciting opportunities for several therapeutic applications. Their tunable properties offer control over their design and function. Starting with biocompatible ions, we synthesized a library of ionic liquids and explored them for various drug delivery applications. Ionic liquids provided unique advantages including overcoming the biological transport barriers of skin, buccal mucosa and the intestinal epithelium. At the same time, they also stabilized proteins and nucleic acids and enabled the delivery of biologics across these barriers. Ionic liquids also provided unique biological functions including adjuvancy towards vaccines and antimicrobial function. I will present an overview of the design features of ionic liquids and novel biomedical applications enabled by these unique materials.
Samir Mitragotri Bio: Samir Mitragotri is the Hiller Professor of Bioengineering and Wyss Professor of Biologically Inspired Engineering at Harvard University. His research is focused on transdermal, oral, and targeted drug delivery systems. He is an elected member of the National Academy of Engineering, National Academy of Medicine and National Academy of Inventors. He is also a foreign member of Indian National Academy of Engineering. He is also an elected fellow of AAAS, CRS, BMES, AIMBE, and AAPS. He is an author of over 350 publications, an inventor on over 200 patent/patent applications, and a Clarivate Highly Cited Researcher. He received his BS in Chemical Engineering from the Institute of Chemical Technology, India and a PhD in Chemical Engineering from the Massachusetts Institute of Technology. He is the Editor-in-Chief of AIChE’s and SBE’s journal Bioengineering and Translational Medicine.
While biologists and chemists race to develop new antibiotics to combat constantly mutating bacteria, predicted to lead to 10 million deaths by 2050, engineers are approaching the problem through a different lens: finding naturally occurring antibiotics in the human genome.
The billions of base pairs in the genome are essentially one long string of code that contains the instructions for making all of the molecules the body needs. The most basic of these molecules are amino acids, the building blocks for peptides, which in turn combine to form proteins. However, there is still much to learn about how — and where — a particular set of instructions are encoded.
Now, bringing a computer science approach to a life science problem, an interdisciplinary team of Penn researchers have used a carefully designed algorithm to discover a new suite of antimicrobial peptides, hiding deep within this code.
The study, published in Nature Biomedical Engineering, was led by César de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, spanning both Penn Engineering and Penn Medicine, and his postdocs Marcelo Torres and Marcelo Melo. Collaborators Orlando Crescenzi and Eugenio Notomista of the University of Naples Federico II also contributed to this work.
“The human body is a treasure trove of information, a biological dataset. By using the right tools, we can mine for answers to some of the most challenging questions,” says de la Fuente. “We use the word ‘encrypted’ to describe the antimicrobial peptides we found because they are hidden within larger proteins that seem to have no connection to the immune system, the area where we expect to find this function.”
Dr. Cynthia Reinhart-King, Engineering, BME, Photo by Joe Howell
Penn Bioengineering alumna Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering and Professor of Biomedical Engineering at Vanderbilt University, was elected the next President of the Biomedical Engineering Society (BMES), the largest professional society for biomedical engineers. Her term as president-elect started at the annual BMES meeting in October 2021.
Reinhart-King graduated with her Ph.D. from Penn Bioengineering in 2006. She studied in the lab of Daniel Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and Chemical and Biomolecular Engineering as a Whitaker Fellow and went on to complete postdoctoral training as an Individual NIH NRSA postdoctoral fellow at the University of Rochester. Prior to joining Vanderbilt, she was on the faculty of Cornell University and received tenure in the Department of Biomedical Engineering. The Reinhart-King lab at Vanderbilt “uses tissue engineering, microfabrication, novel biomaterials, model organisms, and tools from cell and molecular biology to study the effects of mechanical and chemical changes in tissues during disease progression.”
Reinhart-King gave the 2019 Grace Hopper Distinguished Lecture, sponsored by the Department of Bioengineering. This lecture series recognizes successful women in engineering and seeks to inspire students to achieve at the highest level. She is a recipient of numerous prestigious awards, including the Rita Schaffer Young Investigator Award in 2010, an NSF CAREER Award, and the Mid-Career Award in 2018 from BMES.
“BMES is facing many challenges, like many societies, as we deal with the hurdles associated with COVID-19 and inequities across society. We must continue to address those challenges. However, we are also in a terrific window of having robust membership, many members who are eager to get involved with the society’s activities, and a national lens on science and scientists. One of my goals will be to identify and create opportunities for our members to help build the reach of the society and its member.”
Read “Cynthia Reinhart-King is president-elect of the Biomedical Engineering Society” in Vanderbilt News.
The Department of Materials Science and Engineering’s Eric Detsi will lead a team of researchers, including MSE’s Eric Stach and Russell Composto, to develop more eco-friendly batteries that are based on sodium, rather than lithium.
Rechargeable lithium-ion batteries are becoming more ubiquitous, thanks to their use in emerging applications such as battery electric vehicles and grid-scale energy storage, however, these batteries are inefficiently manufactured and unsustainably sourced.
The typical battery cell consists of a separator membrane filled with liquid electrolyte, sandwiched between the negative anode and positive cathode. This design has several drawbacks, including a complex and energy-intensive manufacturing process, inefficient recycling, and increased safety risks as the liquid electrolyte is flammable and crystallization between the electrodes can lead to explosions. Finally, there are substantial geopolitical and environmental risks associated with the global supply chain for lithium-ion battery materials, such as cobalt and lithium.
The solid-state battery design addresses these issues. In solid-state batteries, the flammable liquid electrolyte is replaced by a solid electrolyte, making them safer and more energy efficient. Sodium-ion batteries address the issue of sustainable material sourcing as sodium is more abundant than lithium and cobalt, the materials used in lithium-ion batteries. Both solid-state lithium-ion batteries and sodium-ion batteries are very attractive for battery electric vehicles and grid-scale energy storage applications.
However, current solid-state battery designs also suffer from two major drawbacks: a low capacity for power storage and a resistance to charge transfer.
To tackle the unsustainability in battery materials and the inefficiency of the current solid-state design, the National Science Foundation has awarded a team of Penn Engineers $2.7 Million in funding through its Future Manufacturing program. The team will be led by Eric Detsi, Stephenson Term Assistant Professor in the Department of Materials Science and Engineering (MSE), and will include Eric Stach, Professor in MSE and Director of the Laboratory for Research on the Structure of Matter, and Russell Composto, Howell Family Faculty Fellow and Professor in MSE with appointments in the Departments of Bioengineering and Chemical and Biomolecular Engineering.
“Our team will investigate a novel ‘Eco Manufacturing’ route to a 3D solid-state sodium-ion battery based on polymer solid-electrolytes,” says Detsi. “Our Eco Manufacturing approach will enable us to create batteries from only abundant elements, achieve ultralong battery cycle life, prevent sodium-dendrite-induced short-circuiting by using a ‘self-healing’ metal anode that can transform into liquid when the battery is operating, and efficiently recycle the battery’s anode and cathode. We will also improve the manufacturing process by using time- and energy-efficient processes including direct ink writing, solid-state conversion, and infiltration.”
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.
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).
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.
Speaker: Emma Chory, Ph.D.
Postdoctoral Fellow
Sculpting Evolution Laboratory
Massachusetts Institute of Technology
Date: Thursday, October 21, 2021
Time: 3:30-4:30 PM EDT
Zoom – check email for link or contact ksas@seas.upenn.edu
Room: Moore 216
Abstract: Evolution occurs when selective pressures from the environment shape inherited variation over time. Within the laboratory, evolution is commonly used to engineer proteins and RNA, but experimental constraints have limited our ability to reproducibly and reliably explore key factors such as population diversity, the timing of environmental changes, and chance. We developed a high-throughput system for the analytical exploration of molecular evolution using phage-based mutagenesis to evolve many distinct classes of biomolecules simultaneously. In this talk, I will describe the development of our open-source python:robot integration platform which enables us to adjust the stringency of selection in response to real-time evolving activity measurements and to dissect the historical, environmental, and random factors governing biomolecular evolution. Finally, I will talk about our many on-going projects which utilize this system to evolve previously intractable biomolecules using novel small-molecule substrates to target the undruggable proteome.
Emma Chory Bio: Emma Chory is a postdoctoral fellow in the Sculpting Evolution Group at MIT, advised by Kevin Esvelt and Jim Collins. Emma’s research utilizes directed evolution, robotics, and chemical biology to evolve biosynthetic pathways for the synthesis of novel peptide-based therapeutics. Emma obtained her PhD in Chemical Engineering in the laboratory of Gerald Crabtree at Stanford University. She is the recipient of the NSF Graduate Research Fellowship and a pre- and postdoctoral NIH NRSA Fellowship.
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.
