New Insights into the Mechanisms of Tumor Growth

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3d render of cells secreting exosomes
A team of researchers led by the School of Arts & Science’s Wei Guo offers new insights into a mechanism that promotes tumor growth. “This information could be used to help clinicians diagnose cancers earlier in the future,” says Guo.

In many instances, the physical manifestation of cancers and the ways they are subsequently diagnosed is via a tumor, tissue masses of mutated cells and structures that grow excessively. One of the major mysteries in understanding what goes awry in cancers relates to the environments within which these structures grow, commonly known as the tumor microenvironment.

These microenvironments play a role in facilitating tumor survival, growth, and spread. Tumors can help generate their own infrastructure in the form of vasculature, immune cells, signaling molecules, and extracellular matrices (ECMs), three-dimensional networks of collagen-rich support scaffolding for a cell. ECMs also help regulate cellular communications, and in the tumor microenvironment ECMs can be a key promoter of tumor growth by providing structural support for cancerous cells and in modulating signaling pathways that promote growth.

Now, new research led by the School of Arts & Science’s Wei Guo and published in the journal Nature Cell Biology has bridged the complex structural interactions within the tumor microenvironment to the signals that trigger tumor growth. The researchers studied cancerous liver cells grown on ECMs of varying stiffness and discovered that the stiffening associated with tumor growth can initiate a cascade that increases the production of small lipid-encapsulated vesicles known as exosomes.

“Think of these exosomes as packages that each cell couriers out, and, depending on the address, they get directed to other cells,” says Ravi Radhakrishnan, professor of bioengineering in the School of Engineering and Applied Science and a co-author of the paper.

“By recording the number of packages sent, the addresses on these packages, their contents, and most importantly, how they’re regulated and generated, we can better understand the relationship between a patient’s tumor microenvironment and their unique molecular signaling signatures, hinting at more robust personalized cancer therapies,” Radhakrishnan says.

While studying exosomes in relation to tumor growth and metastasis has been well-documented in recent years, researchers have mostly focused on cataloging their characteristics rather than investigating the many processes that govern the creation and shuttling of exosomes between cells. As members of Penn’s Physical Sciences Oncology Center (PSOC), Guo and Radhakrishnan have long collaborated on projects concerning tissue stiffness. For this paper, they sought to elucidate how stiffening promotes exosome trafficking in cancerous intracellular signaling.

“Our lab previously found that high stiffness promotes the secretion of exosomes,” says Di-Ao Liu, co-first author of the paper and a graduate student in the Guo Lab. “Now, we were able to model the stiffening processes through experiments and identify molecular pathways and protein networks that cause this, which better links ECM stiffening to cancerous signaling.”

Read the full story in Penn Today.

Alexander Buffone Appointed Assistant Professor at New Jersey Institute of Technology

Alexander Buffone, Ph.D.

Penn Bioengineering is proud to congratulate Alexander Buffone, Ph.D. on his appointment as Assistant Professor in the Department of Biomedical Engineering at New Jersey Institute of Technology. His appointment began in the Spring of 2022.

Buffone got his Ph.D. in Chemical Engineering from SUNY Buffalo in Buffalo, NY in 2012, working with advisor Sriram Neelamegham, Professor of Chemical and Biological Engineering. Buffone completed previous postdoctoral studies at Roswell Park Comprehensive Cancer Center with Joseph T.Y. Lau, Distinguished Professor of Oncology in the department of Cellular and Molecular Biology. Upon coming to Penn in 2015, Buffone has worked in the Hammer Lab under advisor Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering, first as a postdoc and later a research associate. Buffone also spent a year as a Visiting Scholar in the Center for Bioengineering and Tissue Regeneration, directed by Valerie M. Weaver, Professor at the University of California, San Francisco in 2019.

While at Penn, Buffone was a co-investigator on an R21 grant through the National Institutes of Health (NIH) which supported his time as a research associate. Buffone is excited to start his own laboratory where he plans to train a diverse set of trainees.

Buffone’s research area lies at the intersection of genetic engineering, immunology, and glycobiology and addresses how to specifically tailor the trafficking and response of immune cells to inflammation and various diseases. The work seeks to identify and subsequently modify critical cell surface and intracellular signaling molecules governing the recruitment of various blood cell types to distal sites. The ultimate goal of his research is to tailor and personalize the innate and adaptive immune response to specific diseases on demand.

“None of this would have been possible without the unwavering support of all of my mentors, past and present, and most especially Dan Hammer,” Buffone says. “His support in helping me transition into an independent scientist and his understanding of my outside responsibilities as a dad with two young children is truly the reason why I am standing here today. It’s a testament to Dan as both a person and a mentor.”

Taimoor Qazi Appointed Assistant Professor at Purdue University

Taimoor H. Qazi, Ph.D.

The Department of Bioengineering is proud to congratulate Taimoor H. Qazi, Ph.D. on his appointment as Assistant Professor in the Weldon School of Biomedical Engineering at Purdue University. Qazi’s appointment will begin in Fall 2022.

Qazi obtained his Ph.D. at the Technical University of Berlin and the Charité Hospital in Berlin, Germany working on translational approaches for musculoskeletal tissue repair using biomaterials and stem cells under the co-advisement of Georg Duda, Director of the Berlin Institute of Health and David Mooney, Mercator Fellow at Charité – Universitätsmedizin Berlin. After arriving at Penn in 2019, Qazi performed research on microscale granular hydrogels in the Polymeric Biomaterials Laboratory of Jason Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. While conducting postdoctoral research, Qazi also collaborated with the groups of David Issadore, Associate Professor in Bioengineering and in Electrical and Systems Engineering, and Daeyeon Lee, Professor and Evan C. Thompson Term Chair for Excellence in Teaching in Chemical and Biomolecular Engineering and member of the Penn Bioengineering Graduate Group. Qazi’s postdoctoral research was supported through a fellowship from the German Research Foundation, and resulted in several publications in high-profile journals, including Advanced Materials, Cell Stem Cell, Small, and ACS Biomaterials Science and Engineering.

“Taimoor has done really fantastic research as a postdoctoral fellow in the group,” says Burdick. “Purdue has a long history of excellence in biomaterials research and will be a great place for him to build a strong research program.”

Qazi’s future research program will engineer biomaterials to make fundamental and translational advances in musculoskeletal tissue engineering, including the study of how rare tissue-resident cells respond to spatiotemporal signals and participate in tissue repair, and developing modular hydrogels that permit minimally invasive delivery for tissue regeneration. The ultimate goal is to create scalable, translational, and biologically inspired healthcare solutions that benefit a patient population that is expected to grow manifold in the coming years.

Qazi is looking to build a strong and inclusive team of scientists and engineers with diverse backgrounds interested in tackling problems at the interface of translational medicine, materials science, bioengineering, and cell biology, and will be recruiting graduate students immediately. Interested students can contact him directly at thqazi@seas.upenn.edu.

“I am excited to launch my independent research career at a prestigious institution like Purdue,” says Qazi. “Being at Penn and particularly in the Department of Bioengineering greatly helped me prepare for the journey ahead. I am grateful for Jason’s mentorship over the years and the access to resources provided by Jason, Dave Issadore, Ravi, Dave Meany and other faculty which support the training and professional development of postdoctoral fellows in Penn Bioengineering.”

Congratulations to Dr. Qazi from everyone at Penn Bioengineering!

César de la Fuente Receives 2022 RSEQ Young Investigator Award

César de la Fuente, PhD

César de la Fuente, Presidential Assistant Professor in Psychiatry, Bioengineering, Microbiology, and in Chemical and Biomolecular Engineering has been honored with a 2022 Young Investigator Award by the Royal Spanish Society of Chemistry (RSEQ) for his pioneering research efforts to combine the power of machines and biology to help prevent, detect, and treat infectious diseases.

Read the RSEQ’s announcement here.

This story originally appeared in Penn Medicine News’s Awards & Accolades post for April 2022.

 

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.

BE Seminar: “Tissue-Inspired Synthetic Biomaterials” (Shelly Peyton)

Shelly R. Peyton, Ph.D.

Speaker: Shelly R. Peyton, Ph.D.
Professor, Armstrong Professional Development Professor
Chemical Engineering, Biomedical Engineering Adjunct
College of Engineering
University of Massachusetts Amherst

Date: Thursday, December 9, 2021
Time: 3:30-4:30 PM EST
Zoom – check email for link
This seminar will be held virtually, but students registered for BE 699 can gather to watch in Moore 216.

Abstract: Improved experimental model systems are critically needed to better understand cancer progression and bridge the gap between lab bench proof-of-concept studies, validation in animal models, and eventual clinical application. Many methods exist to create biomaterials, including hydrogels, which we use to study cells in contexts more akin to what they experience in the human body. Our lab has multiple approaches to create such biomaterials, based on combinations of poly(ethylene glycol) (PEG) with peptides and zwitterions. In this presentation, I will discuss our synthetic approaches to building life-like materials, how we use these systems to grow cells and understand how a cell’s environment, particularly the extracellular matrix regulates cancer cell growth, dormancy, and drug sensitivity.

Shelly Peyton Bio: Shelly Peyton is the Armstrong Professor and Graduate Program Director, and chair of the Diversity, Equity, and Inclusion (DEI) committee of Chemical Engineering at the University of Massachusetts Amherst. She is co-director of the Models 2 Medicine Center in the Institute for Applied Life Sciences. She received her B.S. in Chemical Engineering from Northwestern University in 2002 and went on to obtain her MS and PhD in Chemical Engineering from the University of California, Irvine. She was then an NIH Kirschstein post-doctoral fellow in the Biological Engineering department at MIT before starting her academic appointment at UMass in 2011. Shelly leads an interdisciplinary group of engineers and molecular cell biologists seeking to create and apply novel biomaterials platforms toward new solutions to grand challenges in human health. Her lab’s unique approach is using our engineering expertise to build simplified models of human tissue with synthetic biomaterials. They use these systems to understand 1) the physical relationship between metastatic breast cancer cells and the tissues to which they spread, 2) the role of matrix remodeling in drug resistance, and 3) how to create bioinspired mechanically dynamic and activatable biomaterials. Among other honors for her work, Shelly was a 2013 Pew Biomedical Scholar, received a New Innovator Award from the NIH, and she was awarded a CAREER grant from the NSF. Shelly is co-PI with Jeanne Hardy on the Biotechnology (BTP) NIH T32 program and is a co-PI of the PREP program at UMass, which brings students from URM groups to UMass for a 1-year post-BS study to help prepare them for graduate school.

Yogesh Goyal Selected as 2021 STAT Wunderkind

Yogesh Goyal, Ph.D.

Yogesh Goyal, Ph.D.,  a postdoctoral researcher in Genetics and Bioengineering, has been selected as a 2021 STAT Wunderkind, which honors the “next generation of scientific superstars.” Goyal’s research is centered around developing novel mathematical and experimental frameworks to study how a rare subpopulation of cancer cells are able to survive drug therapy and develop resistance, resulting in relapse in patients. In particular, his work provides a view of different paths that single cancer cells take when becoming resistant, at unprecedented resolution and scale. This research aims to help devise novel therapeutic strategies to combat the challenge of drug resistance in cancer.

Goyal is a Jane Coffin Childs Postdoctoral Fellow in the systems biology lab of Arjun Raj, Professor in Bioengineering and Genetics at Penn. He will begin an appointment as Assistant Professor in the Department of Cell and Developmental Biology (CDB) in the Feinberg School of Medicine at Northwestern University in spring 2022.

Read the announcement in Penn Medicine News.

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.

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.