Noordergraaf and Blair Student Scholars Share Their Summer 2022 Research

Each year, the the Department of Bioengineering seeks exceptional candidates to conduct summer research in bioengineering with the support of two scholarships: the Abraham Noordergraaf Student Summer Bioengineering Research Fund and the Blair Undergraduate Research Fund in the Department of Bioengineering. These scholarships provide a living stipend for students to conduct research on campus in a Penn research lab under the mentorship of a faculty member. The Abraham Noordergraaf Student Summer Bioengineering Research Fund provides financial support for undergraduate or graduate summer research opportunities in bioengineering with a preference for study in the area of cardiovascular systems. Dr. Noordergraaf, who died in 2014, was a founding member and first chair of Penn Bioengineering. The Blair Undergraduate Research Fund in the Department of Bioengineering supports three to five undergraduate research scholars each year with the support of Dr. James C. Blair II. After a competitive round of proposals, the following six scholars were chosen for the Summer 2022 semester. Keep reading below for the research abstracts and bios of the awardees.

The Blair Undergraduate Research Fund in the Department of Bioengineering (Blair Scholars)

Ella Atsavapranee

Student: Ella Atsavapranee (BE Class of 2023)

PI: Michael J. Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation, Bioengineering

“Lipid nanoparticle-mediated delivery of RAS protease to inhibit cancer cell growth”

Mutations in RAS, a family of proteins found in all human cells, drive a third of cancers, including many pancreatic, colorectal, and lung cancers. However, there are still no therapies that can effectively prevent RAS from causing tumor growth. Recently, a protease was engineered to specifically degrade active RAS, offering a promising new tool for treating these cancers. However, many protein-based therapies still cannot be effectively delivered to patients. Lipid nanoparticles (LNPs), which were used in the Pfizer-BioNTech and Moderna COVID-19 vaccines, have emerged as a promising platform for safe and effective delivery of both nucleic acids and proteins. We formulated a library of LNPs using different cationic lipids. We characterized the LNPs by size, charge, and pKa, and tested their ability to deliver fluorescently labeled protease. The LNPs were able to encapsulate and deliver a RAS protease, successfully reducing proliferation of colon cancer cells.

Ella is a senior from Maryland studying bioengineering and chemistry. She works in Dr. Michael Mitchell’s lab, developing lipid nanoparticles to deliver proteins that reduce cancer cell proliferation. She has also conducted research on early-stage cancer detection and therapy monitoring (at Stanford University) and drug delivery across the blood-brain barrier for neurodegenerative diseases (at University of Maryland). She is passionate about translational research, science communication, and promoting diversity in STEM.

Chiadika Eleh

Student: Chiadika Eleh (BE and CIS Class of 2024)

PI: Eric J. Brown, Associate Professor of Cancer Biology, Perelman School of Medicine

“Investigating Viability in ATR and WEE1 Inhibitor Treated Ovarian Cancer Cells”

High-grade serous ovarian cancers (HGSOCs) are an aggressive subtype of ovarian cancer, accounting for up to 80% of all ovarian cancer-related deaths. More than half of HGSOCs are homologous recombination deficient; thus, they lack a favorable response when treated with common chemotherapeutic trials. Therefore, new treatment strategies must be developed to increase the life expectancy and quality of life of HGSOC patients. To address the lack of effective treatment options, the Brown Lab is interested in combining ATR and WEE1 inhibition (ATRi/WEE1i) to target HGSOC cells. It has previously been shown that low-dose ATRi/WEE1i is an effective treatment strategy for CCNE1-amplified ovarian cancer-derived PDX tumors (Xu et al., 2021, Cell Reports Medicine). Therefore, the next step is to characterize the HGSOC-specific response to ATRi/WEE1i treatment. This project aims to characterize the viability phenotype of ovarian cancer (OVCAR3) cells in the presence of ATRi/WEE1i in both single and combination treatments. With further research, Eleh hopes to prove the hypothesis low-dose combination ATRi/WEE1i treatment will result in the synergistic loss of viability in OVCAR3 cells. This goal will be achieved through the treatment of OVCAR3 cells with ranging doses of ATRi and Wee1i over 24 and 48 hour time intervals. We hope that this data will help set a treatment baseline that can be used for all OVCAR30-based viability experiments in the future.

Chiadika Eleh is a Bioengineering and Computer Science junior and a member of Penn Engineering’s Rachleff Scholar program. As a Blair Scholar, she worked in Dr. Eric Brown’s cancer biology lab, where she studied cell cycle checkpoint inhibitors as a form of cancer treatment.

Gloria Lee

Student: Gloria Lee (BE and PHYS Class of 2023)

PI: Yi Fan, Associate Professor of Radiation Oncology, Perelman School of Medicine, and member of the Penn Bioengineering Graduate Group

“Tbc1d2b regulates vascular formation during development and tissue repair after ischemia”

The mechanisms behind endothelial cells forming blood vessels remains unknown. We have identified Tbc1d2b as a protein that is integral to the regulation of vascular formation. In order to investigate the role of Tbc1d2b in tubule formation, fibrin gel bead assays will be conducted to evaluate how the presence of Tbc1d2b is required for angiogenesis. Fibrin gel bead assays simulate the extracellular matrix environment to support the in vitro development of vessels from human umbilical vein endothelial cells (HUVEC) coated on cytodex beads. In order to confirm the success of angiogenesis, immunostaining for Phalloidin and CD31 will be conducted. After confirmation that fibrin gel bead assays can produce in vitro tubules, sgRNA CRISPR knockout of Tbc1d2b will be performed on HUVEC cells which will then be used to conduct more fibrin gel bead assays. We hypothesize that HUVEC with the Tbc1d2b knockout phenotype will be unable to form tubules while wild type HUVEC will be able to.

Gloria Lee is a rising senior studying Bioengineering and Physics in the VIPER program from Denver, Colorado. Her research in Dr. Yi Fan’s lab focuses on the role that proteins play in cardiovascular tubule formation.

Abraham Noordergraaf Student Summer Bioengineering Research Fund (Noordergraaf Fellows)

Gary Lin

Student: Gary Lin (Master’s in MEAM Class of 2023)

PI: Michelle J. Johnson, Associate Professor in Physical Medicine and Rehabilitation, Perelman School of Medicine, and in Bioengineering

“Development and Integration of Dynamically Modulating Control Systems in the Rehabilitation Using Community-Based Affordable Robotic Exercise System (Rehab CARES)”

As the number of stroke patients requiring rehabilitative care continues to increase, strain is being put onto the US health infrastructure which already has a shortage of rehabilitation practitioners. To help alleviate this pressure, a cost-effective robotic rehabilitative platform was developed to increase access to rehabilitative care. The haptic TheraDrive, a one-degree of freedom actuated hand crank that can apply assistive and resistive forces, was modified to train pronation and supination at the elbow and pinching of the fingers in addition to flexion and extension of the elbow and shoulder. Two controllers were created including an open-loop force controller and a closed-loop proportional-integral (PI) with adaptive control gains based on subject performance in therapy-game tasks as well as galvanic skin response. Stroke subjects (n=11) with a range of cognitive and motor impairment completed 4 therapy games in both adaptive and non-adaptive versions of the controllers (n=8) while measuring force applied on the TheraDrive handle. Resulting normalized average power versus Upper Extremity Fugl-Meyer (UE-FM) and Montreal Cognitive Assessment (MoCA) correlation analyses showed that power was strongly correlated with UE-FM in 2 of the conditions and moderately correlated with the other 6 while MoCA was moderate correlated to 2 of the conditions and weakly correlated to the rest. Mann-Whitney U-tests between adaptive and non-adaptive versions of each therapy game showed no significant differences with regards to power between controller types (p<0.05).

Gary is a master’s student in the School of Engineering studying Mechanical Engineering and Applied Mechanics with a concentration in Robotic and Mechatronic systems. His research primarily focuses on developing affordable rehabilitation robotics for use in assessment and game-based therapies post neural injury. Many of his interests revolve around the design of mechatronic systems and the algorithms used to control them for use in healthcare spaces.

Priya Shah

Student: Priya Shah (BE Class of 2024)

PI: Alex J. Hughes, Assistant Professor in Bioengineering

“Optogenetic Control of Developing Kidney Cells for Future Treatment of End-Stage Renal Disease”

This project sought to build from prior research in the Hughes Lab on the geometric and mechanical consequences of kidney form on cell and tissue-scale function. While the developmental trajectory of the kidney is well understood, little is currently known about many factors affecting nephron progenitor differentiation rate. Insufficient differentiation of nephron progenitor cells during kidney formation can result in lower nephron number and glomerular density, which is a risk factor for progression to end-stage renal disease later in life. Prior studies indicated that the amount of nephron differentiation – and thus function of the adult kidney – is correlated to the packing of ureteric tubule tips present at the surface of the kidney. Building off of research conducted in the Bugaj Lab, we found that inserting an optogenetic construct into the genome of human embryonic kidney (HEK) cells allowed us to manipulate the contraction of those cells through exposing them to blue light. Manipulating the contraction of the cells allows for the manipulation of the packing of ureteric tubule tips at the kidney surface. We used a lentiviral vector to transduce HEK293 cells with the optogenetic construct and witnessed visible contraction of the cells when they were exposed to blue light. Future work will include using CRISPR-Cas9 to introduce the optogenetic construct into IPS cells.

Priya is a junior studying bioengineering and had the opportunity to work on manipulating developing kidney cells using an optogenetic construct in the Hughes Lab this summer. She is thrilled to continue this research throughout the coming school year. Outside of the lab, Priya is involved with the PENNaach dance team and the Society of Women Engineers, as well as other mentorship roles.

Cosette Tomita

Student: Cosette Tomita (Master’s in MEAM Class of 2023)

PI: Mark Anthony Sellmyer, Assistant Professor, Radiology, Perelman School of Medicine and member of the Penn Bioengineering Graduate Group

“Expression and Characterization of an Anti-Aβ42 scFv”

Background: Amyloid Beta (Aβ42) fibrils contribute to the pathology of Alzheimer’s Disease. Numerous monoclonal antibodies have been developed against Aβ42. In this study we have designed and expressed a short chain variable fragment specific to Aβ42 (Anti-Aβ42 scFv). To characterize our anti-Aβ42 scFv we have performed structural analysis using transmission electron microscopy (TEM) and binding kinetics using microscale thermophoresis (MST) compared to commercially available antibodies 6E10, Aducanumab, and an IgG isotype control. The goal of this study is to determine if labeling densities and binding constants for Aducanumab and anti-Aβ42 scFv are not significantly different.

Method: To characterize Aβ42 fibril associated antibodies we used negative stain TEM. Aβ42 fibrils were stained on a glow discharged copper grid, and incubated with gold conjugated anti-Aβ42 scFv, 6E10—which binds all Aβ species, aducanumab, or IgG isotype control. Labeling densities were calculated as the number of fibril-associated gold particles per 1 μm2 for each image. Next, we used microscale thermophoresis determine the binding kinetics. Antibodies or anti-Aβ42 scFv were labeled with Alexa Fluor-647 and unlabeled Aβ42 was titrated in a serial dilution over 16 capillaries. The average fluorescence intensity was plotted against the antibody or scFv concentration and the curves were analyzed using the GraphPad Prism software to calculate the dissociation constant (KD) values.

Results: We found a significant difference, tested with a one-way ANOVA (P <0.0001), in gold particle associated Aβ fibrils per 1 μm2 between anti-Aβ42 scFv, 6E10, aducanumab, and IgG isotype control. Further analysis of aducanumab and 6CO3 with unpaired student t-test indicates significant differences in fibril associated gold particles between aducanumab vs. 6E10 (P=0.0003), Aducanumab vs. Isotype control (P <0.0001), anti-Aβ42 scFv vs 6E10 (p=0.0072), and anti-Aβ42 scFv vs Isotype Control (P=0.0029) with no significant difference in labeling densities between Aducanumab and anti-Aβ42 scFv. The expected KD values from MST were 1.8μM for Aducanumab and anti-Aβ42 scFv, 10.3nM for 6E10 and no expected binding for the isotype control. The experimental KD values for anti-Aβ42 scFv and 6E10 are 0.1132μM and 1.467μM respectively. The KD value for Isotype control was undetermined, as expected, however, the KD for Aducanumab was undetermined due to suboptimal assay conditions. Due to confounding variables in the experimental set up such as the use of Aβ1-16 compared to Aβ42 and the use of different fluorophores—5-TAMRA, Alexa Fluor 647 or FITC— the experimental KD values were off by several orders of magnitude.

Conclusion: We have illustrated similar labeling densities between Aducanumab and our anti-Aβ42 scFv. In the future, we will further optimize the MST assay conditions and compare the KD values obtained by MST with other techniques such as surface plasma resonance.

Cosette was born and raised in Chicago land area. Go Sox! She attended University of Missouri where she majored in Chemistry and Biology. She synthesized sigma-2 radiotracers and developed advanced skills in biochemical techniques in Dr. Susan Lever’s lab.  After graduation, she moved to NJ to work at Lantheus, a radiopharmaceutical company. She missed academia and the independence of program and project development, so she came to work at the Penn Cyclotron facility before entering the Bioengineering master’s program.

Microbes That Cause Cavities Can Form Superorganisms Able to ‘Crawl’ and Spread On Teeth

by Katherine Unger Baillie

Hyun (Michel) Koo

A cross-kingdom partnership between bacteria and fungi can result in the two joining to form a “superorganism” with unusual strength and resilience. It may sound like the stuff of science fiction, but these microbial groupings are very much part of the here and now.

Found in the saliva of toddlers with severe childhood tooth decay, these assemblages can effectively colonize teeth. They were stickier, more resistant to antimicrobials, and more difficult to remove from teeth than either the bacteria or the fungi alone, according to the research team, led by University of Pennsylvania School of Dental Medicine scientists.

What’s more, the assemblages unexpectedly sprout “limbs” that propel them to “walk” and “leap” to quickly spread on the tooth surface, despite each microbe on its own being non-motile, the team reported in the journal Proceedings of the National Academy of Sciences

“This started with a very simple, almost accidental discovery, while looking at saliva samples from toddlers who develop aggressive tooth decay,” says Hyun (Michel) Koo, a professor at Penn Dental Medicine and a co-corresponding author on the paper. “Looking under the microscope, we noticed the bacteria and fungi forming these assemblages and developing motions we never thought they would possess: a ‘walking-like’ and ‘leaping-like’ mobility. They have a lot of what we call ‘emergent functions’ that bring new benefits to this assemblage that they could not achieve on their own. It’s almost like a new organism—a superorganism—with new functions.”

Read the full story in Penn Today.

Hyun (Michel) Koo is a professor in the Department of Orthodontics and the divisions of Community Oral Health and Pediatric Dentistry in the School of Dental Medicine, co-founder of the Center for Innovation & Precision Dentistry (CiPD) at the University of Pennsylvania, and member of the Penn Bioengineering Graduate Group.

Penn Bioengineering Alumna Cynthia Reinhart-King Invited to White House Summit

Cynthia Reinhart-King

Cynthia Reinhart-King, Cornelius Vanderbilt Professor of Engineering and Professor of Biomedical Engineering at Vanderbilt University, was one of a handful of experts invited to take part in the White House Summit in Biotechnology and Biomanufacturing on September 14, 2022 in Washington, D.C. Reinhart-King and her colleagues gathered to discuss “bio-based solutions to global challenges ranging from food security and climate change to health security and supply chain disruptions.”

Reinhart-King is an alumna of Penn Bioengineering, graduating with her doctorate in 2006.  She delivered the Grace Hopper Lecture for Penn Engineering in 2019, and was named President-Elect of the Biomedical Engineering Society (BMES), the largest professional society for biomedical engineers, in 2021.

Read “Preeminent engineering researcher takes part in national summit on biotechnology and biomanufacturing” in Vanderbilt University Research News.

A Robot Made of Sticks

Kristina García

Devin Carroll, a doctoral candidate in the School of Engineering and Applied Sciences, is designing a modular robot called StickBot, which may be adapted for rehabilitation use in global public health settings.

Stickbot, a small robot composed of sticks, circuitry, actuators, a microcontroller, and a motor driver, lashed together with string.
StickBot in walking mode, using the sticks as legs to propel itself across the table.

In late summer, just as the leaves were starting to crisp and curl in the heat, Devin Carroll walked out of his apartment, looked on the ground, and picked up a couple of sticks that he thought might work for his robot. About half an inch thick and the length of an adult hand, he stripped the three sticks of their bark and lashed them with string to StickBot, a modular robot composed of circuitry, actuators, a microcontroller, and a motor driver.

Powered by four AA batteries, connected by a maze of wires and blinking lights, StickBot’s wooden arms now thump up and over, powering the robot across the table at Penn’s General Robotics, Automation, Sensing & Perception (GRASP) Lab, where Carroll is a Ph.D. candidate in the School of Engineering and Applied Sciences.

Controlling the robot using an app he designed, Carroll shows how StickBot can pivot from using the sticks as legs in “crawler mode,” to using them as arms. In “grasper mode,” the sticks are attached to a controller plate on one side to form a hinge joint while moving with their free end to hold a cup upright.

Rather than a static, singular invention, StickBot is an idea, a flexible system that can be reconfigured in a variety of ways. A modular robot, StickBot’s components can be added, adjusted, and discarded as needed.

Read the full story in Penn Engineering Today.

This article features quotes from Michelle Johnson, Associate Professor in Physical Medicine and Rehabilitation in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Sciences, and Director of the Rehabilitation Robotics Lab.

 

Defining Neural “Representation”

by Marilyn Perkins

Neuroscientists frequently say that neural activity ‘represents’ certain phenomena, PIK Professor Konrad Kording and postdoc Ben Baker led a study that took a philosophical approach to tease out what the term means.

Monitors Show EEG Reading and Graphical Brain Model. In the Background Laboratory Man Wearing Brainwave Scanning Headset Sits in a Chair with Closed Eyes. In the Modern Brain Study Research Laboratory
Neuroscientists use the word “represent” to encompass multifaceted relationships between brain activity, behavior, and the environment.

One of neuroscience’s greatest challenges is to bridge the gaps between the external environment, the brain’s internal electrical activity, and the abstract workings of behavior and cognition. Many neuroscientists rely on the word “representation” to connect these phenomena: A burst of neural activity in the visual cortex may represent the face of a friend or neurons in the brain’s memory centers may represent a childhood memory.

But with the many complex relationships between mind, brain, and environment, it’s not always clear what neuroscientists mean when they say neural activity “represents” something. Lack of clarity around this concept can lead to miscommunication, flawed conclusions, and unnecessary disagreements.

To tackle this issue, an interdisciplinary paper takes a philosophical approach to delineating the many aspects of the word “representation” in neuroscience. The work, published in Trends in Cognitive Sciences, comes from the lab of Konrad Kording, a Penn Integrates Knowledge University Professor and senior author on the study whose research lies at the intersection of neuroscience and machine learning.

“The term ‘representation’ is probably one of the most common words in all of neuroscience,” says Kording, who has appointments in the Perelman School of Medicine and School of Engineering and Applied Science. “But it might mean something very different from one professor to another.”

Read the full story in Penn Today.

Konrad Kording is a Penn Integrates Knowledge University Professor with joint appointments in the Department of Neuroscience the Perelman School of Medicine and in the Department of Bioengineering in the School of Engineering and Applied Science.

Ben Baker is a postdoctoral researcher in the Kording lab and a Provost Postdoctoral Fellow. Baker received his Ph.D. in philosophy from Penn.

Also coauthor on the paper is Benjamin Lansdell, a data scientist in the Department of Developmental Neurobiology at St. Jude Children’s Hospital and former postdoctoral researcher in the Kording lab.

Funding for this study came from the National Institutes of Health (awards 1-R01-EB028162-01 and R01EY021579) and the University of Pennsylvania Office of the Vice Provost for Research.

CEMB Researchers Find that Disease Can Change the Physical Structure of Cells

by Ebonee Johnson

In these super-resolution images of tendon cell nuclei, the color coding represents chromatin density map, from low density in blue to high density in red. Comparing a healthy human tendon cell nucleus (left) to one diagnosed with tendinosis (right) shows that disease alters the spatial localization and compaction of chromatin.

Researchers from Penn’s Center for Engineering Mechanobiology (CEMB) have discovered that cells change the physical structure of their genome when they’re affected by disease.

In a recent study published in Nature Biomedical Engineering, the team detailed what they found when they closely observed the nucleus of cells inside connective tissues deteriorating as a result of tendinosis, which is the chronic condition that results from a tendon repeatedly suffering small injuries that don’t heal correctly. Using the latest super-resolution imaging techniques, they found that the tendon cells involved in maintaining the tissue’s structure in a diseased microenvironment improperly reorder their chromatin — the DNA-containing material that chromosomes are composed of — when attempting to repair.

This and other findings highlighted in the report point to the possibility of new treatments, such as small-molecule therapies, that could restore order to the affected cells.

“Interestingly, we were able to explain the role of mechanical forces on the 3-D organization of chromatin by developing a theory that integrates fundamental thermodynamic principles (physics) with the kinetics of epigenetic regulation (biology),” said study co-author and CEMB Director Vivek Shenoy in a news release from Penn Medicine News.

The CEMB, one of 18 active interdisciplinary research centers funded by the National Science Foundation’s Science and Technology Center (STC) program, brings together dozens of researchers from Penn Engineering and the Perelman School of Medicine, as well as others spread across campus and at partner institutions around the world.

With its funding recently renewed for another five years, the CEMB has entered  into a new phase of its mission, centered on the nascent concept of “mechanointelligence,” which is exemplified by studies like this one. While mechanobiology is the study of the physical forces that govern the behavior of cells and their communication with their neighbors, mechanointelligence adds another layer of complexity: attempting to understand the forces that allow cells to sense, remember and adapt to their environments.

Ultimately, harnessing these forces would allow researchers to help multicellular organisms — plants, animals and humans — better adapt to their environments as well.

Read “Aberrant chromatin reorganization in cells from diseased fibrous connective tissue in response to altered chemomechanical cues” at Nature Biomedical Engineering.

Read “The Locked Library: Disease Causes Cells to Reorder Their DNA Incorrectly” at Penn Medicine News.

This story originally appeared in Penn Engineering Today.

Vivek Shenoy is Eduardo D. Glandt President’s Distinguished Professor in Materials Science and Engineering, Bioengineering, and in Mechanical Engineering and Applied Mechanics.

‘Curious Minds: The Power of Connection’

Twin siblings and scholars Dani S. Bassett of Penn and Perry Zurn of American University collaborated over half a dozen years to write “Curious Minds: The Power of Connection.” (Image: Tony and Tracy Wood Photography)

With appointments in the Departments of Bioengineering and Electrical and Systems Engineering, as well as the Department of Physics and Astronomy in Penn Arts & Science, and the Departments of Neuroscience and Psychiatry in Penn Perelman’s School of Medicine, Dani S. Bassett is no stranger to following the thread of an idea, no matter where it might lead.

Curious Minds book cover

Those wide-ranging fields and disciplines orbit around an appropriate central question: how does the tangle of neurons in our brains wire itself up to learn new things? Bassett, J. Peter Skirkanich Professor and director of the Complex Systems Lab, studies the relationship between the shape of those networks of neurons and the brain’s abilities, especially the way the shape of the network grows and changes with the addition of new knowledge.

 

To get at the fundamentals of the question of curiosity, Bassett needed to draw on even more disciplines. Fortunately, they didn’t have to look far; Bassett’s identical twin is Perry Zurn, a professor of philosophy at American University, and the two have investigated the many different ways a person can exhibit curiosity.

Bassett and Zurn have now published a new book on the subject. In Curious Minds: The Power of Connection, the twins draw on their previous research, as well as an expansive network of ideas from philosophy, history, education and art.

In an interview with The Guardian, Bassett explains how these threads wove together:

“It wasn’t clear at the beginning of our careers that we would even ever have a chance to write a book together because our areas were so wildly different,” Bassett says – but then, as postgraduates, Zurn was studying the philosophy of curiosity while Bassett was working on the neuroscience of learning. “And so that’s when we started talking. That talking led to seven years of doing research together,” Bassett says. “This book is a culmination of that.”

How exactly do philosophy and neuroscience complement each other? It all starts with the book’s first, and most deceptively simple question: what is curiosity? “Several investigators in science have underscored that perhaps the field isn’t even ready to define curiosity and how it’s different from other cognitive processes,” says Bassett. The ambiguity in the neuroscience literature motivated Bassett to turn to philosophy, “where there are really rich historical definitions and styles and subtypes that we can then put back into neuroscience and ask: ‘Can we see these in the brain?’”

Curious Minds: The Power of Connection is available now. Read Amelia Tait’s review “Are you a busybody, a hunter or a dancer? A new book about curiosity reveals all,” in The Guardian. 

This story originally appeared in Penn Engineering Today.

2022 Career Award Recipient: Michael Mitchell

by Melissa Pappas

Michael Mitchell (Illustration by Melissa Pappas)

Michael Mitchell, J. Peter and Geri Skirkanich Assistant Professor of Innovation in the Department of Bioengineering, is one of this year’s recipients of the National Science Foundation’s CAREER Award. The award is given to early-career faculty researchers who demonstrate the potential to be role models in their field and invest in the outreach and education of their work.

Mitchell’s award will fund research on techniques for “immunoengineering” macrophages. By providing new instructions to these cells via nanoparticles laden with mRNA and DNA sequences, the immune system could be trained to target and eliminate solid tumors. The award will also support graduate students and postdoctoral fellows in his lab over the next five years.

The project aligns with Mitchell’s larger research goals and the current explosion of interest in therapies that use mRNA, thanks to the technological breakthroughs that enabled the development of COVID-19 vaccines.

“The development of the COVID vaccine using mRNA has opened doors for other cell therapies,” says Mitchell. “The high-priority area of research that we are focusing on is oncological therapies, and there are multiple applications for mRNA engineering in the fight against cancer.”

A new wave of remarkably effective cancer treatments incorporates chimeric antigen receptor T-cell (CAR-T) therapy. There, a patient’s T-cells, a type of white blood cell that fights infections, are genetically engineered to identify, target and kill individual cancer cells that accumulate in the circulatory system.

However, despite CART-T therapy’s success in treating certain blood cancers, the approach is not effective against cancers that form solid tumors. Because T-cells are not able to penetrate tumors’ fibrous barriers, Mitchell and his colleagues have turned to another part of the immune system for help.

Read the full story in Penn Engineering Today.

Penn Medicine CAR T Therapy Expert Carl June Receives 2022 Keio Medical Science Prize

by Brandon Lausch

The award from Japan’s oldest private university honors outstanding contributions to medicine and life sciences.

Richard W. Vague Professor in Immunotherapy Carl June.

Carl June, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center, has been named a 2022 Keio Medical Science Prize Laureate. He is recognized for his pioneering role in the development of CAR T cell therapy for cancer, which uses modified versions of patients’ own immune cells to attack their cancer.

The Keio Medical Science Prize is an annual award endowed by Keio University, Japan’s oldest private university, which recognizes researchers who have made an outstanding contribution to the fields of medicine or the life sciences. It is the only prize of its kind awarded by a Japanese university, and eight laureates of this prize have later won the Nobel Prize. Now in its 27th year, the prize encourages the expansion of researcher networks throughout the world and contributes to the well-being of humankind.

“Dr. June exemplifies the spirit of curiosity and fortitude that make Penn home to so many ‘firsts’ in science and medicine,” said Penn President Liz Magill. “His work provides hope to cancer patients and their families across the world, and inspiration to our global community of physicians and scientists who are working to develop the next generation of treatments and cures for diseases of all kinds.”

Read the full story in Penn Today.

June is a member of the Penn Bioengineering Graduate Group. Read more stories featuring June’s research here.

Training the Next Generation of Scientists on Soft Materials, Machine Learning and Science Policy

by Melissa Pappas

Developing new soft materials requires new data-driven research techniques, such as autonomous experimentation. Data regarding nanometer-scale material structure, taken by X-ray measurements at a synchrotron, can be fed into an algorithm that identifies the most relevant features, represented here as red dots. The algorithm then determines the optimum conditions for the next set of measurements and directs their execution without human intervention. Brookhaven National Laboratory’s Kevin Yager, who helped develop this technique, will co-teach a course on it as part of a new Penn project on Data Driven Soft Materials Research.

The National Science Foundation’s Research Traineeship Program aims to support graduate students, educate the STEM leaders of tomorrow and strengthen the national research infrastructure. The program’s latest series of grants are going toward university programs focused on artificial intelligence and quantum information science and engineering – two areas of high priority in academia, industry and government.

Chinedum Osuji, Eduardo D. Glandt Presidential Professor and Chair of the Department of Chemical and Biomolecular Engineering (CBE), has received one of these grants to apply data science and machine learning to the field of soft materials. The grant will provide five years of support and a total of $3 million for a new Penn project on Data Driven Soft Materials Research.

Osuji will work with co-PIs Russell Composto, Professor and Howell Family Faculty Fellow in Materials Science and Engineering, Bioengineering, and in CBE, Zahra Fakhraai, Associate Professor of Chemistry in Penn’s School of Arts & Sciences (SAS) with a secondary appointment in CBE, Paris Perdikaris, Assistant Professor in Mechanical Engineering and Applied Mechanics, and Andrea Liu, Hepburn Professor of Physics and Astronomy in SAS, all of whom will help run the program and provide the connections between the multiple fields of study where its students will train.

These and other affiliated faculty members will work closely with co-PI Kristin Field, who will serve as Program Coordinator and Director of Education.

Read the full story in Penn Engineering Today.