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.

This Week in BioE (June 29, 2017)

Bioengineering Organ Systems

Two news stories this week detailed how bioengineering and biomedical engineering are transforming how human organ systems could be better manipulated for positive effects on health.

organ systemsOne of the critical organ transplant shortages  in medicine is the gap between patients needing a liver transplant (around 13,000 each year) and the those receiving a transplant (about 7,000). For many years, bioengineers tried to build liver tissue in sophisticated 2D and 3D structures. Yet we never really knew how nature ‘interpreted’ these structures. A research team at Cincinnati Children’s Hospital led by Takanori Takebe, MD, reported in Nature that mimicking the 3D shape of the liver was a critical part of making engineered organoids of liver show the same behavior as liver tissue in vivo. These findings show just how important form is for function in nature, bringing us a step closer to alleviating the pressure on organ transplants lists by providing engineering organs.

Not all organs need completely reconstructed replacements. Another critical target organ in the tissue engineering field is the pancreas, which is critical in regulating insulin release.  The nationwide increase in diabetes is only placing more emphasis on finding technologies to augment pancreatic function. Engineers at Duke report in Nature Biomedical Engineering that they could control glucose levels for over a week with a single injection of a new compound they synthesized in the lab.  Rather than many daily injections of insulin for controlling glucose levels in diabetics, this could lead to far less frequent injection.

Machine Diagnosis

We hear quite a bit about Big Data nowadays. This captures a very large field that includes methods to analyze bits of data reliably and quickly to establish patterns (i.e., machine learning) that can help us uncover very new and interesting relationships. Nearly all of this work focuses on narrow data streams, which means the data are largely linked to each other within a category. One example of a narrow data stream is the collection of different types of imaging scans (CT, MRI, PET) from the same patient, collated and compared to better establish how different areas of the brain function. Another example of a narrow data stream is the data contained in a patient’s electronic health record, where it includes facts from the patient’s visits with their physician and specialists.

One interesting thread that is emerging in Big Data is when one starts to cross narrow data streams and create ‘data fabric.’  This means that scientists and engineers are cross-correlating data that seem incompatible with each other, yet they are proving amazingly predictive.  One recent example is when we cross the analysis of speech — one of the earliest machine learning applications — with genetic screening data from patients. Remarkably, scientists at the University of Wisconsin-Madison developed an automated screening system that could analyze audio recordings and determine with 81% accuracy whether the speaker had Fragile X syndrome, a genetic disorder that can have a range of cognitive effects, indicated by genetic screening data. Creating these types of data fabrics could be very powerful in the future because it can use a relatively easy and accessible technology (speech recognition) as an early indicator for more through disease confirmation (genetic testing) and subsequent intervention.

Similarly, these data fabrics are allowing us to reduce our own variability in diagnosing diseases. Penn BE alum Anant Madabhushi developed an algorithm at Case Western Reserve University that was 100% accurate at identifying breast cancer by scanning mammograms, exceeding human performance. Technologies such as these that eliminate the possibility of human error could greatly decrease the rates of delayed or faulty diagnosis. Replacing physicians with computers ? I don’t think so. We all need the human touch, especially when it comes to finding out why we are sick. Capturing errors that humans make? I think so.

A Quick Note

Speaking of Penn alumni, Craig Simmons, Ph.D., who was a postdoctoral fellow in the lab of Penn BE secondary faculty member Peter F. Davies, has been named the interim director of the Institute of Biomaterials & Biomedical Engineering at the University of Toronto. His appointment begins next week. Congratulations to Dr. Simmons!