BE Seminar: “Ionic Liquid-based Therapeutics” (Samir Mitragotri)

Samir Mitragotri, Ph.D.

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.

Penn Researchers Show ‘Encrypted’ Peptides Could be Wellspring of Natural Antibiotics

by Melissa Pappas

César de la Fuente, Ph.D.

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.”

Read the full story in Penn Engineering Today.

Penn Bioengineering Alumna Cynthia Reinhart-King is President Elect of BMES

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.

In a Q&A on the BMES Blog, Reinhart-King said that:

“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.

NSF Grant Will Support Research into Sustainable Manufacturing of 3D Solid-state Sodium-ion Batteries and Battery Workforce Training

by Melissa Pappas

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.”

Read the full story in Penn Engineering Today.

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.

BE Seminar: “Phage and Robotics-Assisted Biomolecular Evolution” (Emma Chory)

Emma Chory, Ph.D.

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.

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.

Yogesh Goyal Appointed Assistant Professor at Northwestern University

Yogesh Goyal, Ph.D.

The Department of Bioengineering is proud to congratulate Yogesh Goyal on his appointment as Assistant Professor in the Department of Cell and Developmental Biology (CDB) in the Feinberg School of Medicine at Northwestern University. His lab will be housed within the Center for Synthetic Biology. His appointment will begin in Spring 2022.

Yogesh grew up in Chopra Bazar, a small rural settlement in Jammu and Kashmir, India. He received his undergraduate degree in Chemical Engineering from the Indian Institute of Technology Gandhinagar. Yogesh joined Princeton University for his Ph.D. in Chemical and Biological Engineering, jointly mentored by Professors Stanislav Shvartsman and Gertrud Schüpbach. Yogesh is currently a Jane Coffin Childs Postdoctoral Fellow in the lab of Arjun Raj, Professor in Bioengineering and Genetics at Penn.

“I am so excited for Yogesh beginning his faculty career,” Raj says. “He is a wonderful scientist with a sense of aesthetics. His work is simultaneously significant and elegant, a powerful combination.”

With a unique background in engineering, developmental biology, biophysical modeling, and single-cell biology, Yogesh develops quantitative approaches to problems in developmental biology and cancer drug resistance. As a postdoc, Yogesh developed theoretical and experimental lineage tracing approaches to study how non-genetic fluctuations may arise within genetically identical cancer cells and how these fluctuations affect the outcomes upon exposure to targeted therapy drugs. The Goyal Lab at Northwestern will “combine novel experimental, computational, and theoretical frameworks to monitor, perturb, model, and ultimately control single-cell variabilities and emergent fate choices in development and disease, including cancer and developmental disorders.”

“I am excited to start a new chapter in my academic career at Northwestern University,” Goyal says. “I am grateful for my time at Penn Bioengineering, and I thank my mentor Arjun Raj and the rest of the lab members for making this time intellectually and personally stimulating.”

Congratulations to Dr. Goyal from everyone at Penn Bioengineering!

Penn Dental Medicine, Penn Engineering Award First IDEA Prize to Advance Oral Health Care Innovation

Henry Daniell and Daeyeon Lee

by Beth Adams

Penn Dental Medicine and Penn Engineering, which teamed earlier this year to launch the Center for Innovation and Precision Dentistry (CiPD), recently awarded the Center’s first IDEA (Innovation in Dental Medicine and Engineering to Advance Oral Health) Prize. Dr. Henry Daniell, W.B. Miller Professor and Vice Chair in the Department of Basic & Translational Sciences at Penn Dental Medicine, and his collaborator, Dr. Daeyeon Lee, Professor of Chemical and Biomolecular Engineering at Penn Engineering, are the inaugural recipients, awarded the Prize for a project titled “Engineered Chewing Gum for Debulking Biofilm and Oral SARS-CoV-2.”

“The IDEA Prize was created to support Penn Dental and Penn Engineering collaboration, and this project exemplifies the transformative potential of this interface to develop new solutions to treat oral diseases,” says Dr. Michel Koo, Professor in the Department of Orthodontics and Divisions of Pediatric Dentistry and Community Oral Health at Penn Dental Medicine and Co-Director of the CiPD.

“The prize is an exciting opportunity to unite Drs. Lee and Daniell and their vision to bring together state-of-the-art functional materials and drug-delivery platforms,” adds Dr. Kathleen Stebe, CiPD Co-Director and Goodwin Professor of Engineering and Applied Science at Penn Engineering.

Open to faculty from Penn Dental Medicine and Penn Engineering, the IDEA Prize, to be awarded annually, supports collaborative teams investigating novel ideas using engineering approaches to kickstart competitive proposals for federal funding and/or private sector/industry for commercialization. Awardees are selected based on originality and novelty; the impact of the proposed innovation of oral/craniofacial health; and the team composition with complementary expertise. Indeed, the project of Drs. Daniell and Lee reflects all three.

The collaborative proposal combines Dr. Daniell’s novel plant-based drug development/delivery platform with Dr. Lee’s novel polymeric structures to create an affordable, long-lasting way to reduce dental biofilms (plaque) and oral SARS-CoV-2 transmission using a uniquely consumer-friendly delivery system — chewing gum.

“Oral diseases afflict 3.5 billion people worldwide, and many of these conditions are caused by microbes that accumulate on teeth, forming difficult to treat biofilms,” says Dr. Daniell. “In addition, saliva is a source of pathogenic microbes and aerosolized particles transmit disease, including COVID-19, so there is an urgent need to develop new methods to debulk pathogens in the saliva and decrease their aerosol transmission.”

Continue reading at Penn Dental Medicine News.

N.B. Henry Daniell and Daeyeon Lee are members of the Penn Bioengineering Graduate Group.

New Grant Aims to Broaden Participation in Cutting-Edge Materials Research

University of Puerto Rico’s Edgardo Sánchez (left) and Penn graduate Zhiwei Liao working in the lab of Daeyeon Lee. Via the Advancing Device Innovation through Inclusive Research and Education program, researchers from Penn and the University of Puerto Rico will continue their materials science collaboration while supporting STEM career pathways for underrepresented groups. (Image credit: Felice Macera).

The National Science Foundation (NSF) has awarded grants to eight research teams to support partnerships that will increase diversity in cutting-edge materials research, education, and career development. One of those teams is Penn’s Laboratory for Research on the Structure of Matter (LRSM) and the University of Puerto Rico (UPR), whose long-running collaboration has now received an additional six years of support.

With the goal of supporting partnerships between minority-serving educational institutions and leading materials science research centers, NSF’s Partnership for Research & Education in Materials (PREM) program funds innovative research programs and provides institutional support to increase recruitment, retention, and graduation by underrepresented groups as well as providing underserved communities access to materials research and education.

‘Research at the frontier’

With this PREM award, known as the Advancing Device Innovation through Inclusive Research and Education (ADIIR) program, researchers from Penn and UPR’s Humacao and Cayey campuses will conduct research on the properties of novel carbon-based materials with unique properties, and will study the effects of surface modification in new classes of sensors, detectors, and purification devices.

Thanks to this collaboration of more than 20 years, both institutions have made significant scientific and educational progress aided by biannual symposia and regular pre-pandemic travel between both institutions before the pandemic, resulting in a rich portfolio of publications, conference presentations, patents, students trained, and outreach programs.

“Together we have been publishing good papers that have impact, and we’ve really cultivated a culture of collaboration and friendship between our institutions,” says Penn’s Arjun Yodh, former director of the LRSM. “Our goal is to carry out research at the frontier and, in the process, nurture promising students from Puerto Rico and Penn.”

Ivan Dmochowski, a chemistry professor at Penn who has been involved with PREM for several years, says that this program has helped his group connect with experts in Puerto Rico whose skills complement his group’s interests in protein engineering. Dmochowski has also hosted UPR faculty members and students in his lab and also travelled to Puerto Rico before the pandemic to participate in research symposia, seminars, and outreach events.

“I’ve had students who have benefitted from being a co-author on a paper or having a chance to mentor students, and the faculty we’ve interacted with are exceptional,” Dmochowski says. “There’s a lot of benefit for both me and my students, and I’ve enjoyed our interactions both personally and scientifically.”

Penn’s Daeyeon Lee, a chemical and biomolecular engineering professor who has been involved with PREM for several years, regularly hosts students and faculty from UPR while working on nanocarbon-based composite films for sensor applications. The success of this collaboration relies on unique materials made by researchers at UPR combined with a method for processing them into composite structures developed in Lee’s lab.

“What I really admire about people at PREM, both faculty and students, is their passion,” says Lee. “I think that’s had a really positive impact on my students and postdocs who got to interact with them because they got to see the passion that the students brought.”

Read the full story in Penn Today.

Daeyeon Lee is a professor and the Evan C Thompson Term Chair for Excellence in Teaching in the Department of Chemical and Biomolecular Engineering and a member of the Bioengineering Graduate Group in Penn’s School of Engineering and Applied Science.

Arjun Yodh is the James M. Skinner Professor of Science in the Department of Physics & Astronomy in Penn’s School of Arts & Sciences and a member of the Bioengineering Graduate Group in Penn’s School of Engineering and Applied Science.