Single-cell Cancer Detection Project Wins 2021 NEMO Prize

This scProteome-seq array shows separated protein biomarkers (green and magenta spots) from thousands of single cells.

Penn Health-Tech’s Nemirovsky Engineering and Medicine Opportunity (NEMO) Prize awards $80,000 to support early-stage ideas joining engineering and medicine. The goal of the prize is to encourage collaboration between the University of Pennsylvania’s Perelman School of Medicine and the School of Engineering and Applied Science by supporting innovative ideas that might not receive funding from traditional sources.

This year, the NEMO Prize has been awarded to a team of researchers from Penn Engineering’s Department of Bioengineering. Their project aims to develop a technology that can detect multiple cancer biomarkers in single cells from tumor biopsy samples.

As cancer cells grow in the body, one of the characteristics that influences tumor growth and response to treatment is cancer cell state heterogeneity, or differences in cell states. Methods that rapidly catalogue cell heterogeneity may be able to detect rare cells responsible for tumor growth and drug resistance.

Single-cell transcriptomics (scRNA-seq) is the standard method for studying cell states; by amplifying and analyzing the cell’s complement of RNA sequences at a given time, researchers can get a snapshot of what proteins the cell is in the process of making. However, this method does not fully capture the function of the cell. The field of proteomics, which captures the actual protein content of cells along with post-translational modifications, provides a better picture of the cell’s function, but single-cell proteomic methods with the same sensitivity as scRNA-seq do not currently exist.

Alex Hughes, Lukasz Bugaj and Andrew Tsourkas

This collaborative project, which joins Assistant Professors Alex Hughes and Lukasz Bugaj, as well as Professor Andrew Tsourkas, aims to change that by developing multiplexed, sensitive and highly specific single-cell proteomics technologies to advance our understanding of cancer, its detection and its treatment.

This new technology, called scProteome-seq, builds from Hughes’s previous work.

“My specific expertise here is as an inventor of single-cell western blotting, which is the core technology that our team is building on,” says Hughes. “Single-cell proteomics technologies of this type have a track-record of commercial translation for applications in basic science and clinical automation, so our approach has a high potential for real-world impact.”

The current technology from Hughes’ lab separates proteins in cells by their molecular weight and “blots” them on a piece of paper. Improvements to this technology included in this project will remove the limitation of using light-emitting dyes to detect different proteins and instead use DNA barcodes to differentiate them.

Read the full story in Penn Engineering Today.

Penn Anti-Cancer Engineering Center Will Delve Into the Disease’s Physical Fundamentals

by Evan Lerner

A colorized microscope image of an osteosarcoma shows how cellular fibers can transfer physical force between neighboring nuclei, influencing genes. The Penn Anti-Cancer Engineering Center will study such forces, looking for mechanisms that could lead to new treatments or preventative therapies.

Advances in cell and molecular technologies are revolutionizing the treatment of cancer, with faster detection, targeted therapies and, in some cases, the ability to permanently retrain a patient’s own immune system to destroy malignant cells.

However, there are fundamental forces and associated challenges that determine how cancer grows and spreads. The pathological genes that give rise to tumors are regulated in part by a cell’s microenvironment, meaning that the physical push and pull of neighboring cells play a role alongside the chemical signals passed within and between them.

The Penn Anti-Cancer Engineering Center (PACE) will bring diverse research groups from the School of Engineering and Applied Science together with labs in the School of Arts & Sciences and the Perelman School of Medicine to understand these physical forces, leveraging their insights to develop new types of treatments and preventative therapies.

Supported by a series of grants from the NIH’s National Cancer Institute, the PACE Center is Penn’s new hub within the Physical Sciences in Oncology Network. It will draw upon Penn’s ecosystem of related research, including faculty members from the Abramson Cancer Center, Center for Targeted Therapeutics and Translational Nanomedicine, Center for Soft and Living Matter, Institute for Regenerative Medicine, Institute for Immunology and Center for Genome Integrity.

Dennis Discher and Ravi Radhakrishnan

The Center’s founding members are Dennis Discher, Robert D. Bent Professor with appointments in the Departments of Chemical and Biomolecular Engineering (CBE), Bioengineering (BE) and Mechanical Engineering and Applied Mechanics (MEAM), and Ravi Radhakrishnan, Professor and chair of BE with an appointment in CBE.

Discher, an expert in mechanobiology and in delivery of cells and nanoparticles to solid tumors, and Radhakrishnan, an expert on modeling physical forces that influence binding events, have long collaborated within the Physical Sciences in Oncology Network. This large network of physical scientists and engineers focuses on cancer mechanisms and develops new tools and trainee opportunities shared across the U.S. and around the world.

Lukasz Bugaj, Alex Hughes, Jenny Jiang, Bomyi Lim, Jennifer Lukes and Vivek Shenoy (Clockwise from upper left).

Additional Engineering faculty with growing efforts in the new Center include Lukasz Bugaj, Alex Hughes and Jenny Jiang (BE), Bomyi Lim (CBE), Jennifer Lukes (MEAM) and Vivek Shenoy (Materials Science and Engineering).

Among the PACE Center’s initial research efforts are studies of the genetic and immune mechanisms associated with whether a tumor is solid or liquid and investigations into how physical stresses influence cell signaling.

Originally posted in Penn Engineering Today.

2021 CAREER Award recipient: Alex Hughes, Assistant Professor in Bioengineering

by Melissa Pappas

Alex Hughes (illustration by Melissa Pappas)

The National Science Foundation’s CAREER Award is given to early-career researchers in order to kickstart their careers in innovative and pivotal research while giving back to the community in the form of outreach and education. Alex Hughes, Assistant Professor in Bioengineering and in Cell and Developmental Biology, is among the Penn Engineering faculty members who have received the CAREER Award this year.

Hughes plans to use the funds to develop a human kidney model to better understand how the development of cells and tissues influences congenital diseases of the kidney and urinary tract.

The model, known as an “organoid,” is a lab-grown piece of human kidney tissue on the scale of millimeters to centimeters, grown from cultured human cells.

“We want to create a human organoid structure that has nephrons, the filters of the kidney, that are properly ‘plumbed’ or connected to the ureteric epithelium, the tubules that direct urine towards the bladder,” says Hughes. “To achieve that, we have to first understand how to guide the formation of the ureteric tubule networks, and then stimulate early nephrons to fuse with those networks. In the end, the structures will look like ‘kidney subunits’ that could potentially be injected and fused to existing kidneys.”

The field of bioengineering has touched on questions similar to those posed by Hughes, focusing on drug testing and disease treatment. Some of these questions can be answered with the “organ-on-a-chip” approach, while others need an even more realistic model of the organ. The fundamentals of kidney development and questions such as “how does the development of nephrons affect congenital kidney and urinary tract anomalies?” require an organoid in an environment as similar to the human body as possible.

“We decided to start with the kidney for a few reasons,” says Hughes. “First, because its development is a beautiful process; the tubule growth is similar to that of a tree, splitting into branches. It’s a complex yet understudied organ that hosts incredibly common developmental defects.

“Second,” he says, “the question of how things form and develop in the kidney has major medical implications, and we cannot answer that with the ‘organ-on-a-chip’ approach. We need to create a model that mimics the chemical and mechanical properties of the kidney to watch these tissues develop.”

The fundamental development of the kidney can also answer other questions related to efficiency and the evolution of this biological filtration system.

“We have the tendency to believe that systems in the human body are the most evolved and thus the most efficient, but that is not necessarily true,” says Hughes. “If we can better understand the development of a system, such as the kidney, then we may be able to make the system better.”

Hughes’ kidney research will lay the foundation for broader goals within regenerative medicine and organ transplantation.

Read the full story in Penn Engineering Today.

Alex Hughes Receives the First MIRA Award of Penn SEAS

by Sophie Burkholder

Alex Hughes, Ph.D.

We would like to congratulate Assistant Professor in Bioengineering Alex Hughes, Ph.D., on receiving the Maximizing Investigators’ Research Award (MIRA) from the National Institutes of Health (NIH), which funds investigators to create flexible and forward-thinking research programs. Hughes is the first recipient of this award in Penn’s School of Engineering and Applied Science, marking a major accomplishment for him and his lab.

The award recognizes Hughes’ efforts to create new  tools used for tissue engineering, in particular by fusing concepts from developmental biology into tissue construction efforts. Hughes believes this approach will have impacts on fundamental understanding human disease, leading to new strategies to combat them. Hughes and his lab specifically focus on kidney disease. As Hughes says, “defects in the kidney and urinary tract account for up to a third of all birth defects.” Furthermore, because kidney development involves many different kinds of cell interactions, there’s a gap in understanding exactly how these defects occur.

Unlike other grants that focus on funding projects, the MIRA prioritizes the people behind the research, giving them funding as a sign of faith in the future work they’ll choose to do. “The MIRA has allowed us significant leeway to integrate several complementary approaches here,” Hughes says. Because of this flexibility, Hughes and his lab thinks it will allow them to reach for more innovative and risky approaches in their research, in the hopes that this will lead to a better understanding of kidney defects and modes of treatment for them.

Tissue Folding Processes Further Unraveled

tissue folding
Alex Hughes, Ph.D.

One of the key processes in embryonic development and growth through childhood and adolescence is that of how tissue folds into the specific shapes required for them to function in the body.  For instance, mesenchymal stem cells, which form a variety of tissues including bones, muscles, and fat, are required to “know” what shapes to take on as they form organ systems and other structures. Therefore, a big concern in tissue engineering is determining how to control these processes of tissue folding.

Just in time for his arrival at Penn Bioengineering, Dr. Alex Hughes, a new assistant professor in the department, is the lead author on a new paper in Developmental Cell that explores this concern. The study was coauthored with Dr. Zev Gartner of the University of California, Berkeley, where Dr. Hughes just finished a postdoctoral fellowship. In the paper, the authors used three-dimensional cell-patterning techniques, embryonic tissue explants, and finite element modeling to determine that the folding process involves the interaction of a protein called myosin II with the extracellular matrix, itself the molecular material that provides a structural framework for developing tissues. With the knowledge gained in the initial experiments, the authors were then able to reproduce the tissue folding process in the lab.

“Bioengineers are currently thinking about building tissues,” Dr. Hughes says, “not just at the level of organoids, but at the level of organs in the body. One of my interests at Penn is to harness developmental principles that link these length scales, allowing us to design medically relevant scaffolds and machines.”

Equipped with the knowledge gleaned from this research, future studies could contribute further to the ability to generate tissues and even organ systems in laboratories. Ultimately, this knowledge could revolutionize transplant medicine, as well as variety of other fields.

New Faculty: Interview With Alex Hughes

Alex new faculty
Alex Hughes, Ph.D.

As noted earlier this week, Penn BE will be bringing in three new faculty members over the coming academic year, starting with Alex Hughes, who will start in the fall semester. Here’s the first of our series of podcasts with the new faculty, to come each Friday this month. Enjoy!

(P.S. Apologies for the rough version of the audio. We are still learning!)

New Faculty Joining Penn Bioengineering

We are thrilled to announce the successful recruitment of three (!) new faculty members to the department. We conducted a national faculty search and could not decide on one — we wanted all three of our finalists!  We are very happy that they chose Penn and think we can provide an amazing environment for their education and research programs.

new faculty hughes
Alex Hughes, Ph.D.

Alex Hughes, Ph.D., will join us in the Spring 2018 semester. Dr. Hughes comes to us from the University of California, San Francisco (UCSF), where he is a postdoctoral fellow. Alex’s research regards determining what he calls the “design rules” underlying how cells assemble into tissues during development, both to better understand these tissues and to engineer methods to build them from scratch

new faculty bugaj
Lukasz Bugaj, Ph.D.

Lukasz Bugaj, Ph.D., will arrive in the Spring 2018 semester. Dr. Bugaj is also coming here from UCSF following a postdoc, and his work is in the field of optogenetics — a scientific process whereby light is used to alter protein conformation, thereby giving one a tool to manipulate cells. In particular, Lukasz’s research has established the ability to induce proteins to cluster ‘on demand’ using light, and he wants to use these and other new technologies he invented to study cell signaling in stem cells and in cancer.

new faculty mitchell
Mike Mitchell, Ph.D.

Mike Mitchell, Ph.D., will also join us in the Spring 2018 semester after finishing his postdoctoral fellowship at MIT in the Langer Lab. In his research, Dr. Mitchell seeks to engineer cells in the bone marrow and blood vessels as a way of gaining control over how and why cancer metastasizes. Mike’s work has already had impressive results in animal models of cancer. His lab will employ tools and concepts from cellular engineering, biomaterials science, and drug delivery to fundamentally understand and therapeutically target complex biological barriers in the body.

In the coming month, we’ll feature podcasts of interview with each of the new faculty members, as well as with Konrad Kording, so be sure to keep an eye out for those.

And to our new faculty, welcome to Penn!