Penn is fighting pancreatic cancer

A microscopic view of pancreatic adenocarcinoma. (Image: Emma Furth)

Swept up in a pancreatic cancer diagnosis is inevitably a sense of fear and sadness.

But at Penn, researchers are bringing new hope to this disease. And with patients like Nick Pifani, it’s clear that they’re moving in the right direction.

Pifani, from Delran, New Jersey, first noticed some lingering stomach upset in February 2017. He called his family doctor, concerned—especially given that he was an otherwise healthy marathon runner who was only 42. He was sent to a gastrointestinal specialist. A few weeks later, some crippling stomach pain sent him back to the emergency room and he received an MRI that showed a mass on his pancreas—Stage Three, inoperable, he was told.

He was treated with chemotherapy, along with radiation and, eventually, and after receiving advice from doctors at Penn, his tumor was removed. Thereafter, he realized he had a PALB2 mutation—a cousin of the BRCA gene mutation. At that moment, his long-term needs changed and he found himself seeking specialized care at Penn, where he met Kim Reiss Binder, assistant professor of medicine at the Hospital of the University of Pennsylvania (HUP).

“I’m a planner; I want to understand what [my] potential options are,” Pifani says. “[Reiss Binder] asked why I was there to see her and I explained and quickly I could tell she was—outside of her being remarkably intelligent—a great listener and a compassionate doctor.”

“I have a feeling she worries about me more than I do,” he laughs.

Pifani has now been in remission for two years and four months; he sees Reiss-Binder every three months for checkups. His survival story is inspiring and a sign of momentum, even if a world without pancreatic cancer is still frustratingly out of reach.

Pancreatic cancer at Penn

Pancreatic cancer is the third-leading cause of cancer-related death in the United States, outmatched only by lung cancer (No. 1) and colorectal cancer (No. 2). A person diagnosed with pancreatic cancer is still unlikely to survive past five years—only 9% of survivors do, giving it the highest mortality rate among every major cancer.

In short, pancreatic cancer seldom paves the way for optimistic narratives. Some of the hope that has surfaced, though, is thanks to some talent, dedication to the cause, and hard work at Penn.

A key point of progress in the battle against the disease was made in 2002, when former Assistant Professor of Medicine David Tuveson established a standard model for examining human development of this disease in mice. This model has allowed for a reliable way to study the disease and has influenced progress made here at Penn and elsewhere since.

“There’s been a burst of activity in translational research, from bench to bedside,” explains Ben Stanger, the Hanna Wise Professor in cancer research and director of the Penn Pancreatic Cancer Research Center (PCRC) at the Abramson Cancer Center.

“And there’s a lot of momentum with community building, a dramatic increase in patient volumes, and a dramatic increase in what we know about the cancer,” he says of the status of pancreatic cancer today.

Reiss Binder, meanwhile, explains that one mark of progress at Penn and beyond has been learning about people like Pifani, who have the PALB2 gene, and why they respond differently to treatments than those without it. Platinum-based chemotherapies, for example, are especially effective for people with the PALB2 gene who are battling pancreatic cancer. An ongoing trial at Penn has tested and found some success with using PARP inhibitors—taken orally as an enzyme that fixes single-stranded breaks of DNA—as a maintenance therapy in that same PALB2 demographic after they’ve had chemotherapy. These are less toxic than chemotherapy for patients with the same mutations.

It’s all been slow progress toward better treatments, but there has been progress.

“This is the tip of the iceberg for a disease that we historically have treated with perpetual chemotherapy,” Reiss Binder says. “We owe it to patients to find better options to suppress the cancer but not ruin their quality of life.”

Catching cancer earlier

The consensus on why pancreatic cancer is so deadly? It just can’t be spotted fast enough.

Pancreatic cancer often presents well after it has developed and metastasized, and does so in a way that is not easy to recognize as cancer. Common symptoms include, for example, stomach upset and back pain. And by the time a harder-to-ignore symptom of the cancer surfaces, a sort of yellowing of the skin (a result of a bile duct blockage), it’s likely too late to stop the cancer in its tracks.

One approach to improved detection being tested at Penn, by Research Assistant Professor of Medicine Erica Carpenter, is a liquid biopsy—drawn from a standard blood test. Current means to test for pancreatic cancer—imaging through an endoscopic tube—are invasive and expensive, meaning a common liquid test could transform how many cases are detected early.

Carpenter explains that circulating tumor cells (CTCs) can shed from a tumor that’s adjacent to the wall of a blood vessel; what’s shed then shows up in a blood test. The cells, if detected, can explain more about the nature of the tumor, giving doctors an opportunity to examine characteristics of cancerous cells and decide how to effectively treat a tumor if it can’t be surgically removed. It also allows interpretations of disease burden and the effectiveness of medications—through genome sequencing—that imaging does not.

Ultimately, this gives doctors the potential to track the growth of a tumor before it’s fully developed, all through one tube of blood—detected through an innovative use of technology.

 

David Issadore, Ph.D.

David Issadore, associate professor of bioengineering and electrical and systems engineering in the School of Engineering and Applied Science, has worked since 2017 to develop a chip that detects cancer in the blood, using machine learning to sort through literally hundreds of billions of vesicles and cells, looking for these CTCs. The chip retrieves data and the machine learning developed interprets that data, attempting to make a diagnosis that not only finds pancreatic cancer but also provides information about its progression—and, importantly, whether a patient might benefit from surgery.

Read the full story at Penn Today. Media contact Brandon Baker.

The Optical Society Names Nader Engheta the 2020 Max Born Award Recipient

Nader Engheta, Ph.D.

The Optical Society (OSA) has named Nader Engheta, H. Nedwill Ramsey Professor in the Department of Electrical and Systems Engineering, as the 2020 recipient of the Max Born Award.

Engheta, who also has appointments in the departments of Bioengineering and Materials Science and Engineering, is honored for pioneering contributions to optical metamaterials and nanoscale optics.

“The Born Award recognizes Nader Engheta’s exceptional contributions to the fields of metamaterials, transformation optics and nanophotonics,” said 2020 OSA President Stephen D. Fantone, founder and president of Optikos Corporation. “This honor is emblematic of the pioneering work he has done in near-zero index metamaterials.”

Read the full story on the Penn Engineering blog.

Listen: Danielle Bassett Uses Network Science to Find Links in Human Curiosity

Danielle Bassett, Ph.D.

Danielle Bassett, J. Peter Skirkanich Professor of Bioengineering and Electrical and Systems Engineering, is a curious scientist.

Featured on a recent episode of “Choosing to be Curious” on WERA 96.7 Radio Arlington, Bassett discussed her work in studying curiosity and the potential neural mechanisms behind it. In her work, Bassett strives to re-conceptualize curiosity itself, defining it as not just seeking new bits information, but striving to understand the path through which those bits are connected.

Bassett is a pioneering researcher in the field of network science and how its tools can be applied to understand the brain. Now, Bassett and her research team are using the tools of network science and complex systems theory to uncover what common styles of curiosity people share and how individual styles differ. In addition, the team is exploring if there are canonical types of curiosity among humans or if each person’s curiosity architecture is unique.

This isn’t the first time Bassett has combined the tools of disparate fields to pursue her research. For as long as she can remember, Bassett has been insatiably curious and, while she was homeschooled as a child, she often wandered from one subject to the next and let her own interest guide her path. For Bassett, studying curiosity with the tools of physical, biology, and engineering is a natural step in her research journey.

In her interview with host Lynn Borton, Bassett says:

“What took me to curiosity is the observation that there’s a problem in defining the ways in which we search for knowledge. And that perhaps the understanding of curiosity could be benefitted by a scientific and mathematical approach. And that maybe the tools and conceptions that we have in mathematics and physics and other areas of science are useful for understanding curiosity. Which most people would consider to be more in the world of the humanities than the sciences….“Part of what I’m hoping to do is to illustrate that there are connections between disciplines that seem completely separate. Sometimes some of the best ideas in science are inspired not by a scientific result but by something else.”

To hear more about Bassett’s research on curiosity, listen to the full episode of Choosing to Be Curious.

Originally posted on the Penn Engineering blog.

Melanie Hilman Finds Community in Bioengineering

Penn Bioengineering senior and MEAM submatriculant, Melanie Hilman

Melanie Hilman was born to be a Biomedical Engineer. The daughter of an electrical engineering father and physician mother, Melanie was inspired by her parents work and is now pursuing the intersection of their two careers: bioengineering.

LIFELONG LEARNER

Her passion for engineering began long before Melanie stepped onto Smith Walk.

“I always really loved math and science as a middle school and high school student,” Melanie says.

Melanie quickly discovered that Penn was the perfect place for her. After visiting campus as a prospective student, Melanie knew that she wanted to attend a research-driven university where innovation and discovery was at the top of the curriculum.

“Being in a place so rich with research and really smart minds motivated me to apply here and be a part of this program,” Melanie remembers.

On top of her bioengineering research, Melanie submatriculated into Mechanical Engineering and Applied Mechanics with a focus on Mechanics of Materials because she wants to develop a deep foundation in the mathematical concepts. After gaining this experience, Melanie hopes to conduct complex research and eventually pursue a PhD.

BETWEEN TWO WORLDS

“I really like thinking about the interface between biology and today’s technologies,” Melanie comments. Right now, she’s focused on doing research but she is interested in, one day, developing biomedical technologies for the start-up industry.

As if building the future of bioengineering weren’t enough for Melanie, she is a dedicated member of the Penn community outside of the lab. Throughout her time at Penn, Melanie is a student leader of Penn Hillel, a devoted performer in the Penn Symphony Orchestra and Penn Chamber Music, and a multimedia staff member of the Daily Pennsylvanian. Even when school is out of session, Melanie represents Penn during Alternative Spring Break trips where she took on a leadership position renovating houses in West Virginia. All of this extracurricular work is important to Melanie, as she says these experiences have given her a valuable perspective to carry with her through academic, professional and personal life.

“It makes me feel really fortunate for my upbringing and my experiences,” Melanie shares.

Melanie performs at a concert with Penn Symphony Orchestra

WOMEN IN STEM

When asked about her favorite part of being at Penn Engineering, Melanie was certain about her answer: empowered women engineers.

“Having a really strong female engineering network is super valuable to me,” Melanie says.

Melanie says she’s found friendship and support among her fellow women engineers and that working with women is as fun as it is enriching. While Penn Engineering has proved itself to be an inclusive space for Melanie and others, current research shows that only 13% of professional engineers are women, and, among them, biomedical engineering ranks fourth in terms of career path of women engineers. Faced with these jarring numbers, Melanie is even more committed to encouraging other women to join her in STEM.

Most of all, she is grateful for the community she has found on campus.

“I know I’m going to have a good group of friends after I graduate. I have found other women that I hope to have lasting friendships with.”

Armed with friends and research partners, Melanie Hillman may very well turn the tides for women in engineering and usher in a new era of women in the lab who lead the charge for biomedical innovation.

Originally posted on the Penn Engineering blog.

Getting Physical with Developmental Biology Research

macrophages Discher
Dennis Discher, Ph.D.

By Izzy Lopez

While genetics and biochemistry research has dominated the conversation about how human bodies are formed, new research — with an old twist — is proposing that there is another star in the show of human development: mechanical forces.

At the turn of the twentieth century, medical research relied on simple mechanics to explain scientific phenomena, including how human cells morph into shape from embryo to newborn and beyond. As better chemistry techniques and DNA research burst onto the scene, however, the idea that cells could be affected by physical forces took a back seat. Now researchers are referring back to this vintage idea and bringing it into the 21st century.

Dennis Discher, Robert D. Bent Professor in the Departments of Chemical and Biomolecular Engineering, Bioengineering and Mechanical Engineering and Applied Mechanics, was featured in a recent article in Knowable Magazine for his research on the human heart and how mechanical forces exerted on heart cells give the vital organ its necessary stiffness during development.

Read the full story on the Penn Engineering blog.

Dr. Danielle Bassett and Dr. Jason Burdick Named to Highly Cited Researchers List

by Sophie Burkholder

One way to measure the success or influence of a researcher is to consider how many times they’re cited by other researchers. Every published paper requires a reference section listing relevant earlier papers, and the Web of Science Group keeps track of how many times different authors are cited over the course of a year.

Danielle Bassett, Ph.D.

In 2019, two members of the Penn Bioengineering department, Jason Burdick, Ph.D., and Danielle Bassett, Ph.D., were named Highly Cited Researchers, indicating that each of them placed within the top 1% of citations in their field based on the Web of Science’s index. For the past year, only 6,300 researchers were recognized with this honor, a number that makes up a mere 0.1% of researchers worldwide. Bassett’s lab looks at the use of knowledge, brain, and dynamic networks to understand bioengineering problems at a systems-level analysis, while Burdick’s lab focuses on advancements in tissue engineering through polymer design and development.

Robert D. Bent Chair
Jason Burdick, PhD

Burdick’s and Bassett’s naming to the list of Highly Cited Researchers demonstrates that their research had an outsized influence over current work in the field of bioengineering in the last year, and that new innovations continue to be developed from foundations these two Penn researchers created. To be included among such a small percentage of researchers worldwide indicates that Bassett and Burdick are sources of great impact and influence in bioengineering advancements today.

BE Seminar Series: March 5th with Tara L. Deans, Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Speaker: Tara L. Deans, Ph.D.
Assistant Professor
Biomedical Engineering
University of Utah

Date: Thursday, March 5, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Engineering Stem Cells to Create Novel Delivery Vehicles”

 

Abstract:

Synthetic biology has transformed how cells can be reprogrammed, providing a means to reliably and predictably control cell behavior with the assembly of genetic parts into more complex gene circuits. Using approaches and tools in synthetic biology, we are programming stem cells with novel genetic tools to control genes and pathways that result in changes in stem cell fate decisions, in addition to reprogramming terminally differentiated cells to function as unique therapeutic diagnostic and delivery vehicles.

Bio:

Dr. Tara Deans received her PhD from Boston University in Biomedical Engineering. Following her postdoctoral training at Johns Hopkins University, she became an Assistant Professor in Biomedical Engineering at the University of Utah. Currently, Dr. Deans runs an applied mammalian synthetic biology laboratory where her lab focuses on building novel genetic tools to study the mechanisms of stem cell differentiation for the purpose of directing cell fate decisions. Recently, Dr. Deans received four prestigious awards to support this area of research: the NSF CAREER Award, the Office of Naval Research (ONR) Young Investigator Award, the NIH Trailblazer Award and an NIH Director’s New Innovator Award. In addition to her research, Dr. Deans was recently named a STEM Ambassador in the STEM Ambassador Program (STEMAP) at the University of Utah to engage underrepresented groups in STEM fields.

BE Seminar Series: February 27th with Michael Yaszemski, M.D., Ph.D.

Our next Penn Bioengineering seminar will be held this Thursday. We hope to see you there!

Michael Yaszemski, M.D., Ph.D.

Speaker: Michael Yaszemski, M.D., Ph.D.
The Krehbiel Endowed Professor of Orthopedic Surgery and Biomedical Engineering
Mayo Clinic

Date: Thursday, February 27, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

Title: “Musculoskeletal Tissue Engineering”

 

Abstract:

The field of Tissue Engineering/Regenerative Medicine is replete with advances that have been translated to human use. However, our job is not done when a treatment for a specific disease or traumatic event has been invented and translated to humans. In order to be available to the population nationwide (or globally), our novel treatment must be manufactured, transported to the user, and administered by a physician to that user. In addition, novel treatments for rare diseases may not be amenable to manufacture by a company, and perhaps would be best manufactured by an academic medical center. I will discuss these issues that occur after successful translation of a novel treatment to human use, as well as potential strategies to address them.

Bio:

Dr. Michael Yaszemski is the Krehbiel Family Endowed Professor of Orthopedic Surgery and Biomedical Engineering at Mayo Clinic and director of its Polymeric Biomaterials and Tissue Engineering Laboratory. He is a retired USAF Brigadier General. He has served as the president of the Mayo medical staff. He received both bachelor’s and master’s degrees in chemical engineering from Lehigh University in 1977 and 1978, an M.D. from Georgetown University in 1983 and a Ph.D. in chemical engineering from Massachusetts Institute of Technology in 1995.  He served as a member of the Lehigh University Board of Trustees.

How the Bioengineering Department’s Bio-MakerSpace Became a Hub for Start-Ups

by Sophie Burkholder

The George H. Stephenson Foundation Educational Laboratory and Bio-MakerSpace, more commonly known as the Bio-MakerSpace, has recently become a hub for Penn student start-ups that continue after graduation. Beyond offering a home base for projects by Bioengineering majors, the lab is also open to Penn students, regardless of major. Unlike other departmental undergraduate labs, the Bio-MakerSpace encourages interdisciplinary projects and collaborations from students across  all different majors.

Even better, the lab has a neutral policy when it comes to intellectual property (IP), meaning all IP behind student projects belongs to the students instead of the lab or the engineering school. With a wide variety of prototyping equipment, coding and software programs installed on lab computers, and an extremely helpful lab staff, the Bio-MakerSpace provides students of all academic backgrounds the resources to turn their ideas into realities or even businesses, as a recent succession of start-ups founded in the lab has shown.

One of the most successful start-ups to come out of the Bio-MakerSpace in the last few years is Group K Diagnostics, founded by 2017 Bioengineering alumna Brianna Wronko. The company focuses on the use of a point-of-care diagnostic device called KromaHealthTM. Offering a variety of different tests based on the input of a small amount of blood, serum, or urine, the device induces a color change through a series of reactions that can be detected through image processing. Developed in part from Wronko’s senior design project (hence the name “Group K”) and in part from her experience working at an HIV clinic, Group K Diagnostics looks to expand access to care for all populations.

But not all start-ups from the Bio-MakerSpace have origins in senior design projects. Three start-ups from 2019, two of which won the Penn President’s Innovation Prize, all began as independent initiatives from students. InstaHub, founded by 2019 Wharton alumnus Michael Wong with help from Bioengineering doctoral candidate Dayo Adewole, is a company that focuses on the use of snap-on automation for light energy conservation. A simple and easy-to-install device with motion and occupancy sensors, InstaHub aims to reduce energy consumption in a way that’s simpler and cheaper than rewiring projects that might otherwise be required. Here, Adewole shares the way that access to the Bio-MakerSpace provided InstaHub with a helpful platform.

The second start-up from 2019 to come out of the Bio-MakerSpace and win a President’s Innovation Prize is Strella Biotechnology, founded by recent graduate Katherine Sizov (Biology 2019). In developing sensors with the ability to detect ethylene gas emitted by rotting fruits, Strella hopes to reduce the immense amount of food waste due to produce simply going bad in storage. With a patent-pending biosensor that mimics the way ripe fruits detect ethylene emissions of nearby rotting fruits, the technology behind Strella involves both biology and aspects of engineering. In this video, Sizov herself talks about the way that the Bio-MakerSpace opened its doors to her, and allowed her work to really take off with the help of resources she wouldn’t have easily found otherwise.

Yet another start-up to use the Bio-MakerSpace as a launch pad for innovation is BioAlert Technologies, comprised of a group of Penn engineering undergraduate and graduate students, including 2019 Bioengineering alumnus Johnny Forde and current Biotechnology student Marc Rosenberg, who is the startup’s CEO and founder. BioAlert’s innovations are in what they call continuous infection monitoring (CIM) systems, designed to detect infections in patients with diabetic foot ulcers. Often, even when properly bandaged by a doctor, these ulcers run the risk of bacterial infection once a patient returns home and continues to care for the wound. BioAlert uses their platform to assess whether or not a bacterial infection might occur in a given patient’s wound, and uses an app to alert both patients and doctors of it, so that patients can receive the proper response treatment and medication as quickly as possible.

Though each of these start-ups used the resources of the Bio-MakerSpace, they are each interdisciplinary approaches to solving real-world problems today. Paired with other student resources at Penn like courses offered under an Engineering Entrepreneurship minor, knowledge from the nearby Wharton business school professors, and competitions like the Rothberg Catalyzer, the Bio-MakerSpace allows for any student to transform their idea into a reality, and potentially take it to market.

Interested in learning more? Contact the BE Labs.

Computer-generated Antibiotics, Biosensor Band-Aids, and the Quest to Beat Antibiotic Resistance

By Michele W. Berger

Imagine if a computer could learn from molecules found in nature and use an algorithm to generate new ones. Then imagine those molecules could get printed and tested in a lab against some of the nastiest, most dangerous bacteria out there — bacteria quickly becoming resistant to our current antibiotic options.

Or consider a bandage that can sense an infection with fewer than 100 bacterial cells present in an open wound. What if that bandage could then send a signal to your phone letting you know an infection had started and asking you to press a button to trigger the release of the treatment therapy it contained?

These ideas aren’t science fiction. They’re projects happening right now, in various stages, in the lab of synthetic biologist , who joined the University as a Presidential Professor in May 2019. His ultimate goal is to develop the first computer-made antibiotics. But beyond that, his lab — which includes three postdoctoral fellows, a visiting professor, and a handful of graduate students and undergrads — has many other endeavors that sit squarely at the intersection of computer science and microbiology.

Computer-generated antibiotics

Antibiotic resistance is becoming a dangerous problem, both in the United States and worldwide. According to the , each year in the U.S., at least 2.8 million people get infections that antibiotics can’t help, and more than 35,000 die from those infections. Around the world, common ailments like pneumonia and food-borne illness are getting harder to treat.

De la Fuente poses near Penn’s “Biopond”
De la Fuente earned his bachelor’s degree in biotechnology, then a doctorate in microbiology and immunology and a postdoc in synthetic biology and computational biology. Combining these fields led him to the innovative work his lab does today.

New antibiotics are needed, and according to de la Fuente, it’s time to look beyond the traditional approach.

“We’ve relied on nature as a source of antibiotics for many, many years. My whole hypothesis is that nature has perhaps run out of inspiration,” says de la Fuente, who has appointments in the and the . “We haven’t been able to discover any new scaffolds for many years. Can we digitize that information, nature’s chemistry, to be able to create and discover new molecules?”

To do that, his team turned to amino acids, the building blocks of protein molecules. The 20 that occur naturally bond in countless sequences and lengths, then fold to form different proteins. The sequencing possibilities are expansive, more than the number of stars in the universe. “We could never synthesize all of them and just see what happens,” says postdoc Marcelo Melo. “We have to combine the chemical knowledge — decades of chemistry on these tell us how they behave — with the computational side, because a computer can find patterns unlike any human could.”

Using machine learning, the researchers provide the computer with natural molecules that successfully work against bacteria. The computer learns from those examples, then generates new, artificial molecules. “We try this back and forth and hopefully we find patterns, new patterns that we can explore, instead of blindly searching,” Melo says.

The computer can then test each artificial sequence virtually, setting aside the most successful components and tossing the rest, in a form of computational natural selection. Those pieces with the highest potential get used to create new sequences, theoretically producing better and better ones each time.

De la Fuente’s team has seen some promising results already: “A lot of the molecules we’ve synthesized have worked,” he says. “The best ones worked in animal models. They were able to reduce infections in mice — which was pretty cool, given that the computer generated the whole thing.” Still, de la Fuente says the work is years away from producing anything close to a shelf-ready antibiotic.

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