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.

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.

 

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.

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.

The Penn Center for Precision Engineering for Health Announces First Round of Seed Funding

by Melissa Pappas

CPE4H is one of the focal points of Penn Engineering signature initiative on Engineering Health.

The Penn Center for Precision Engineering for Health (CPE4H) was established late last year to accelerate engineering solutions to significant problems in healthcare. The center is one of the signature initiatives for Penn’s School of Engineering and Applied Science and is supported by a $100 million commitment to hire faculty and support new research on innovative approaches to those problems.

Acting on that commitment, CPE4H solicited proposals during the spring of 2022 for seed grants of $80K per year for two years for research projects that address healthcare challenges in several key areas of strategic importance to Penn: synthetic biology and tissue engineering, diagnosis and drug delivery, and the development of innovative devices. While the primary investigators (PIs) for the proposed projects were required to have a primary faculty appointment within Penn Engineering, teams involving co-PIs and collaborators from other schools were eligible for support. The seed program is expected to continue for the next four years.

“It was a delight to read so many novel and creative proposals,” says Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and the Inaugural Director of CPE4H. “It was very hard to make the final selection from a pool of such promising projects.”

Judged on technical innovation, potential to attract future resources, and ability to address a significant medical problem, the following research projects were selected to receive funding.

Evolving and Engineering Thermal Control of Mammalian Cells

Led by Lukasz Bugaj, Assistant Professor in Bioengineering, this project will engineer molecular switches that can be toggled on and off inside mammalian cells at near-physiological temperatures. Successful development of these switches will provide new ways to communicate with cells, an advance that could be used to make safer and more effective cellular therapies.  The project will use directed evolution to generate and find candidate molecular tools with the desired properties. Separately, the research will also develop new technology for manipulating cellular temperature in a rapid and programmable way. Such devices will enhance the speed and sophistication of studies of biological temperature regulation.

A Quantum Sensing Platform for Rapid and Accurate Point-of-Care Detection of Respiratory Viral Infections

Combining microfluidics and quantum photonics, PI Liang Feng, Professor in Materials Science and Engineering and Electrical and Systems Engineering, Ritesh Agarwal, Professor in Materials Science Engineering, and Shu Yang, Joseph Bordogna Professor in Materials Science and Engineering and Chemical and Biomolecular Engineering, are teaming up with Ping Wang, Professor of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine, to design, build and test an ultrasensitive point-of-care detector for respiratory pathogens. In light of the COVID-19 pandemic, a generalizable platform for rapid and accurate detection of viral pathogenesis would be extremely important and timely.

Versatile Coacervating Peptides as Carriers and Synthetic Organelles for Cell Engineering

PI Amish Patel, Associate Professor in Chemical and Biomolecular Engineering, and Matthew C. Good, Associate Professor of Cell and Developmental Biology in the Perelman School of Medicine and in Bioengineering, will design and create small proteins that self-assemble into droplet-like structures known as coacervates, which can then pass through the membranes of biological cells. Upon cellular entry, these protein coacervates can disassemble to deliver cargo that modulates cell behavior or be maintained as synthetic membraneless organelles. The team will design new chemistries that will facilitate passage across cell membranes, and molecular switches to sequester and release protein therapeutics. If successful, this approach could be used to deliver a wide range of macromolecule drugs to cells.

Towards an Artificial Muscle Replacement for Facial Reanimation

Cynthia Sung, Gabel Family Term Assistant Professor in Mechanical Engineering and Applied Mechanics and Computer Information Science, will lead a research team including Flavia Vitale, Assistant Professor of Neurology and Bioengineering, and Niv Milbar, Assistant Instructor in Surgery in the Perelman School of Medicine. The team will develop and validate an electrically driven actuator to restore basic muscle responses in patients with partial facial paralysis, which can occur after a stroke or injury. The research will combine elements of robotics and biology, and aims to produce a device that can be clinically tested.

“These novel ideas are a great way to kick off the activities of the center,” says Hammer. “We look forward to soliciting other exciting seed proposals over the next several years.”

This article originally appeared in Penn Engineering Today.

Center for Innovation & Precision Dentistry Welcomes Inaugural Class to Training Program

The inaugural class of the CiPD NIDCR T90/R90 Postdoctoral Training Program Fellows with Dean Mark Wolff (center); Dr. Michel Koo, Founding Director of CiPD (far right); and CiPD Co-Director Dr. Kathleen Stebe of Penn’s School of Engineering and Applied Science (far left).

With one of its key missions to develop a new generation of scientists at the interface of dental medicine and engineering, the Center for Innovation & Precision Dentistry (CiPD) has selected its inaugural class of fellows for its new postdoctoral training program.

The CiPD was awarded a $2.5 million T90/R90 grant from the National Institute of Dental and Craniofacial Research (NIDCR) last summer to establish the program, recently naming this first cohort of fellows that includes Justin Burrell,  Marshall Padilla,  Zhi Ren, and Dennis Sourvanos.

“We’re hoping this program will promote cross-pollination and create a culture between these two fields to help dentists develop innovative strategies with engineers,” says Penn Dental Medicine’s Michel Koo, Co-Director of CiPD, who launched the Center in 2021 with Co-Director Kathleen Stebe, Richer & Elizabeth Goodwin Professor in Penn Engineering’s Department of Chemical and Biomolecular Engineering. “Dentists can learn from engineering principles and tools, and engineers can understand more about the needs of the dental and craniofacial fields. We’re providing a platform for them to work together to address unmet clinical needs and develop careers in that interface.”

The NIDCR T90/R90 Postdoctoral Training Program aims to specifically focus on the oral microbiome, host immunity, and tissue regeneration, each of which ties into different aspects of oral health, from tooth decay and periodontal disease to the needs of head and neck cancer patients. To advance these areas, emerging approaches, from advanced materials, robotics, and artificial intelligence to tissue engineering, chloroplast- and nanoparticle-based technologies, will be leveraged.

As part of the two-year training, each postdoc will receive co-mentorship from faculty from each school in conjunction with a career development committee of clinicians, basic scientists, as well as engineers. These mentorships will be focused on research outcomes and readying participants to submit grants and compete for positions in academia or industry.

The inaugural class of fellows includes Justin Burrell, a postdoctoral student in the lab of D. Kacy Cullen, Associate Professor of Neurosurgery; Marshall Padilla, a postdoc in the lab of Michael J. Mitchell, Skirkanich Assistant Professor of Innovation in Bioengineering; and Zhi Ren, a postdoc in the lab of Michael Koo; and Dennis Sourvanos, an Advanced Graduate Dental Education resident at Penn Dental Medicine whose research has been co-directed by Timothy C. Zhu, Professor of Radiation Oncology in the Perelman School of Medicine. Cullen, Mitchell, Koo and Zhu are all members of the Penn Bioengineering Graduate Group.

Read more about the inaugural class of postdocs at Penn Dental Medicine News

Center for Engineering Mechanobiology 2.0: Developing ‘Mechanointelligence’

by Evan Lerner

The dynamics governing mechanointelligence vary greatly along time- and length-scales, so detailed models of individual cells and their components are necessary to connect the effects of their physical environments to the downstream effects those forces have on biological processes.

The National Science Foundation’s Science and Technology Center (STC) program is its flagship funding mechanism for organizing interdisciplinary research on cutting-edge topics. Penn’s Center for Engineering MechanoBiology (CEMB) is one of the 18 active STCs, bringing 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 NSF funding now renewed for another five years, the Center is entering into a new phase of its mission, centered on the nascent concept of “mechanointelligence.”

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.

“Mechanointelligence is a key element of a cell’s ability to survive and reproduce,” says CEMB Director and Eduardo D. Glandt President’s Distinguished Professor Vivek Shenoy. “Just like with complex organisms, a cell’s ‘fitness’ depends on its environment, and adapting means rewiring how its genes are expressed.”

Read the full story in Penn Engineering Today.

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

Bioengineering Graduate Jason Andrechak Wins Graduate Leadership Award

Jason Andrechak

Congratulations to recent Penn Bioengineering graduate Jason Andrechak on winning a Graduate Leadership Awards for 2022. Each year a select number of students across the university are recognized for their service and lasting contributions to graduate student life at Penn. Andrechak, one of only ten recipients in 2022, won a 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.” Andrechak won this award for his “service and leadership in advocating for equity and accessibility during the transition to virtual operations and following a period of leadership transition within the Graduate and Professional Student Assembly (GAPSA). ”

Andrechak completed his Ph.D. in Bioengineering in 2022, where he studied macrophage immunotherapy in solid tumors in the lab of Dennis E. Discher, Robert D. Bent Professor in Chemical and Biomolecular Engineering, Bioengineering, and Mechanical Engineering and Applied Mechanics. He was named a National Science Foundation Graduate Research Fellow in 2018. He has actively led the Graduate Association of Bioengineers (GABE) as Community Service & Outreach chair from 2017-2019 and as co-President from 2019-2022. He also served as the Director of Equity & Access for the Graduate & Professional Student Assembly (GAPSA) from 2020-2021, in addition to several other service and advisory roles at the department, school, and university levels.

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

Decoding a Material’s ‘Memory’

by Erica K. Brockmeier

A suspension of particles of different sizes during shearing experiments conducted in the lab of Paulo Arratia, with arrows indicating particle “flow” and trajectories. In a new study published in Nature Physics, researchers detail the relationship between a disordered material’s individual particle arrangement and how it reacts to external stressors. The study also found that these materials have “memory” that can be used to predict how and when they will flow. (Image: Arratia lab)

New research published in Nature Physics details the relationship between a disordered material’s individual particle arrangement and how it reacts to external stressors. The study also found that these materials have “memory” that can be used to predict how and when they will flow. The study was led by Larry Galloway, a Ph.D. student in the lab of Paulo Arratia, and Xiaoguang Ma, a former postdoc in the lab of Arjun Yodh, in collaboration with researchers in the labs of Douglas Jerolmack and Celia Reina.

A disordered material is randomly arranged at the particle-scale, e.g. atoms or grains, instead of being systematically distributed—think of a pile of sand instead of a neatly stacked brick wall. Researchers in the Arratia lab are studying this class of materials as part of Penn’s Materials Research Science & Engineering Center, where one of the program’s focuses is on understanding the organization and proliferation of particle-scale rearrangements in disordered, amorphous materials.

The key question in this study was whether one could observe the structure of a disordered material and have some indication as to how stable it is or when it might begin to break apart. This is known as the yield point, or when the material “flows” and begins to move in response to external forces. “For example, if you look at the grains of a sand castle and how they are arranged, can I tell you whether the wind can blow it over or if it has to be hit hard to fall over?” says Arratia. “We want to know, just by looking at the way the particles are arranged, if we can say anything about the way they’re going to flow or if they are going to flow at all.”

While it has been known that individual particle distribution influences yield point, or flow, in disordered materials, it has been challenging to study this phenomenon since the field lacks ways to “quantify” disorder in such materials. To address this challenge, the researchers collaborated with colleagues from across campus to combine expertise across the fields of experimentation, theory, and simulations.

Read the full story in Penn Today.

The authors are Larry Galloway, Erin Teich, Christoph Kammer, Ian Graham, Celia Reina, Douglas Jerolmack, Arjun Yodh, and Paulo Arratia from Penn; Xiaoguang Ma, previously a postdoc at Penn and now at the Southern University of Science and Technology in Shenzhen, China; and Nathan Keim, previously a postdoc at Penn and now at Pennsylvania State University.

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

Paulo Arratia is a professor in the departments of Mechanical Engineering and Applied Mechanics and Chemical and Biomolecular Engineering in the School of Engineering and Applied Science at the University of Pennsylvania.

Douglas Jerolmack is a professor in the Department of Earth and Environmental Science in Penn’s School of Arts & Sciences and in the Department of Mechanical Engineering and Applied Mechanics at Penn Engineering.

Celia Reina is the William K. Gemmill Term Assistant Professor in the Department of Mechanical Engineering and Applied Mechanics at Penn Engineering.

Penn Bioengineering Celebrates Five Researchers on Highly Cited Researchers 2021 List

The Department of Bioengineering is proud to announce that five of our faculty have been named on the annual Highly Cited Researchers™ 2021 list from Clarivate:

Dani Bassett, Ph.D.

Dani S. Bassett, J. Peter Skirkanich Professor in Bioengineering and in Electrical and Systems Engineering
Bassett runs the Complex Systems lab which tackles problems at the intersection of science, engineering, and medicine using systems-level approaches, exploring fields such as curiosity, dynamic networks in neuroscience, and psychiatric disease. They are a pioneer in the emerging field of network science which combines mathematics, physics, biology and systems engineering to better understand how the overall shape of connections between individual neurons influences cognitive traits.

Robert D. Bent Chair
Jason Burdick, Ph.D.

Jason A. Burdick, Robert D. Bent Professor in Bioengineering
Burdick runs the Polymeric Biomaterials Laboratory which develops polymer networks for fundamental and applied studies with biomedical applications with a specific emphasis on tissue regeneration and drug delivery. The specific targets of his research include: scaffolding for cartilage regeneration, controlling stem cell differentiation through material signals, electrospinning and 3D printing for scaffold fabrication, and injectable hydrogels for therapies after a heart attack.

César de la Fuente, Ph.D.

César de la Fuente, Presidential Assistant Professor in Bioengineering and Chemical & Biomedical Engineering in Penn Engineering and in Microbiology and Psychiatry in the Perelman School of Medicine
De la Fuente runs the Machine Biology Group which combines the power of machines and biology to prevent, detect, and treat infectious diseases. He pioneered the development of the first antibiotic designed by a computer with efficacy in animals, designed algorithms for antibiotic discovery, and invented rapid low-cost diagnostics for COVID-19 and other infections.

Carl June, M.D.

Carl H. June, Richard W. Vague Professor in Immunotherapy in the Perelman School of Medicine and member of the Bioengineering Graduate Group
June is the Director for the Center for Cellular Immunotherapies and the Parker Institute for Cancer Therapy and runs the June Lab which develops new forms of T cell based therapies. June’s pioneering research in gene therapy led to the FDA approval for CAR T therapy for treating acute lymphoblastic leukemia (ALL), one of the most common childhood cancers.

Vivek Shenoy, Ph.D.

Vivek Shenoy, Eduardo D. Glandt President’s Distinguished Professor in Bioengineering, Mechanical Engineering and Applied Mechanics (MEAM), and in Materials Science and Engineering (MSE)
Shenoy runs the Theoretical Mechanobiology and Materials Lab which develops theoretical concepts and numerical principles for understanding engineering and biological systems. His analytical methods and multiscale modeling techniques gain insight into a myriad of problems in materials science and biomechanics.

The highly anticipated annual list identifies researchers who demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top 1% by citations for field and publication year in the Web of Science™ citation index.

Bassett and Burdick were both on the Highly Cited Researchers list in 2019 and 2020.

The methodology that determines the “who’s who” of influential researchers draws on the data and analysis performed by bibliometric experts and data scientists at the Institute for Scientific Information™ at Clarivate. It also uses the tallies to identify the countries and research institutions where these scientific elite are based.

David Pendlebury, Senior Citation Analyst at the Institute for Scientific Information at Clarivate, said: “In the race for knowledge, it is human capital that is fundamental and this list identifies and celebrates exceptional individual researchers who are having a great impact on the research community as measured by the rate at which their work is being cited by others.”

The full 2021 Highly Cited Researchers list and executive summary can be found online here.