Macrophages Engineered Against Cancer Cells

macrophages Discher
Dennis Discher, Ph.D.

Dennis E. Discher, Ph.D., Robert D. Bent Professor in the Department of Chemical and Biomolecular Engineering and a secondary faculty member in the Department of Bioengineering, was the lead author on a recent study that showed that engineered macrophages (a type of immune cell) could be injected into mice, circulate through their bodies, and invade solid tumors in the mice, engulfing human cancers cells in the tumors.

According to Cory Alvey, a graduate student in pharmacology who works in Professor Discher’s lab and the first author on the paper, said, “Combined with cancer-specific targeting antibodies, these engineered macrophages swarm into solid tumors and rapidly drive regression of human tumors without any measurable toxicity.”

Read more here.

This Week in BioE (July 13, 2017)

Devices and Drug Delivery

Abdominal surgery can lead to complications when the intestines are accidentally damaged. One key point in the surgery is during wound closure, when the surgeon must place the final sutures without knowing where the underlying intestine is located. A new material designed by bioengineers can be inserted into the abdomen and protect the intestines from perforations by the surgical needle. Key features of this material include its flexibility to fit into the small incision made during laprascopy and its ability to dissolve naturally within hours upon insertion into the abdominal cavity.  Before it dissolves, the material is tough enough to protect the intestines from puncture, allowing the surgeon to close the incision with much less risk of perforation. So the material is ready when it is needed and disappears soon thereafter.

New materials appear frequently to perform the functions of naturally occurring biological tissues. For decades, several researchers attempted to re-create cartilage outside of the body. Although these artificial cartilage tissues may contain all of the right ‘ingredients’ — i.e., molecules and cells — the tissue is commonly not strong enough to withstand the forces normally experienced by the target tissue.  Recently, researchers invented a process to load the cartilage tissue surrogate while it was fabricated, a departure from the traditional process in which the tissue substitute is mechanically loaded after it is built. Both techniques are designed to make the artificial tissue stronger.  However, this subtle new design step to mechanically load during fabrication makes the cartilage substitute six times stronger than any existing manufacturing technique, raising the possibility that we can build tissue outside the body for use inside the body.

emu egg
An emu egg

Finally, the field is constantly discovering new ways to use historical observations in science. One example was an observation from the analysis of 19,000-year-old DNA from an emu egg, made possible because the DNA was protected from degradation by the calcified material present in the eggshell. This scientific observation to understand the origin of the species inspired bioengineer Bill Murphy at the University of Wisconsin-Madison to create a new method to protect proteins from degradation by incorporating these proteins into mineralized materials. Reminiscent of the mineralized matrix found in the emu eggshell that protected DNA for 19,000 years, the charged mineralized matrix stabilizes the protein structure and significantly improves the stability of the protein. By designing the mineralized material to degrade slowly, this work shows that one can stabilize and release therapeutic proteins over much longer periods than previously possible.

Technological Advances in Cancer Diagnosis and Treatment

Despite tremendous advances in diagnosis and treatment, cancer remains a major public health threat. Surgery is often a key part of cancer treatment, but tumor removal is complicated by the difficulty in producing surgical margins that are free of cancer cells. If cancer cells remain in the margins, it is common for the cancer to return. However, a team of researchers at the University of Washington developed a light-sheet microscope capable of imaging these surgical margins quickly – about 30 minutes. The technology could go a long way toward reducing or eliminating the 20% to 40% of cases of breast cancer in which relapse occurs.

While breast cancer remains the most common cancer among women, proliferation of HPV has resulted in a steadily increasing rate of cervical cancer over past decades. Early screening here is a key to successful treatment, but gynecological examinations are uncomfortable for many women. Failure to schedule a follow-up colposcopy is common following an abnormal Pap smear, resulting in persistently higher rates. A pocket colposcope developed by Duke Biomedical Engineering Professor Nimmi Ramanujam could close this gap in treatment. Although the colposcope must still be rigorously tested, a small group of 15 volunteers who tested the device reported that it was 80% accurate.

New BioE dept at Lehigh

Lehigh University in Bethlehem, Pa., has announced the creation of a Department of Bioengineering. Anand Jagota, a professor formerly in the Department of Chemical Engineering, founded the department and will act as its first chair. In addition to Professor Jagota, 16 professors form the core department faculty.

Welcome to the club, Lehigh!

Mind Control and an Ethical Appeal

mind control brain
A “wiring diagram of the human brain,” produced using diffusion MRI scans of the brain.

A group of four scholars from the University of Pennsylvania, including Bioengineering professor Danielle Bassett, have issued a call in the journal Nature Human Behaviour for greater safeguards for patients as treatments in the field of neuroscience evolve and come ever closer to resembling “mind control.”

“While we don’t believe,” Bassett said, “that the science-fiction idea of mind control, totally overriding a person’s autonomy, will ever be possible, new brain-focused therapies are becoming more specific, targeted and effective at manipulating individuals’ mental states. As these techniques and technologies mature, we need systems in place to make sure they are applied such that they maximize beneficial effects and minimize unwanted side effects.”

Read more at the Penn News Web Site.

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!)

This Week in BioE (July 6, 2017)

Bioengineering of Genes and DNA

Since Watson and Crick published their initial studies detailing the double helix structure of DNA in the early 1960s, what we know about genetics and the nucleic acids underlying them has grown enormously. Consequently, what bioengineering can do with DNA and genes continually expands.

One fascinating bioengineering field that emerged in the past decade was DNA origami, which uses the well-established binding across DNA elements to create three-dimensional structures out of linear DNA sequences. Recent work has utilized this feature of DNA construction to make machines, rather than just parts, out of DNA.

Yonggang Ke, Ph.D., of Georgia Tech/Emory’s Department of Biomedical Engineering, constructed machines made of DNA that consist of arrays of units that can “switch” between “settings” by changing shape. A change in shape of one unit of an array can cause the other units in the array to shift; these changes are stimulated by inserting a previously deleted strand of DNA into the array. Although it has been known for some time that DNA could be used to store and transmit information, Dr. Ke’s research team proved for the first time that these arrays could be shaped physically into machines in the shapes of rectangles and tubes.

genes dna
DNA under a microscope

While we learn more about how to make DNA-based devices, we are also creating new technologies to manipulate DNA more rapidly.  Scientists at Rutgers and Harvard developed a process whereby thousands of genes could be cloned at one time to create enormous libraries of proteins. To achieve this goal, the authors used a technology called LASSO (long-adapter single-strand oligonucleotide) probes, which they have already used to clone a library using a human microbiome sample.

Instead of the traditional process of cloning one gene at a time, the team led by Professor Biju Parekkadan, Ph.D. at Rutgers, invented a technology to clone hundred of genes simultaneously. These cloned DNA segments are much longer than the length of DNA cloned with standard techniques, allowing us to test the functional significance of these much longer DNA segments.  The technology could impact a number of scientific fields because we will finally learn how long stretches of protein function — some parts may degrade other proteins, while other parts will interact and modify other proteins (e.g., phosphorylation, a key process in epigenetics). These new discoveries can be key for discovering new ways to engineer proteins and to manufacture new drugs that mimic the function of nature’s DNA products.

Using Sweat as a Biosensor

While the field learns more about the molecular-level control of DNA, we are also taking advantage of new micro- and nanoscale manufacturing processes to capture diagnostic information from easily accessible body fluids. Many clinical diagnostics use chemical measurements from blood to diagnose a disease or to take corrective action. This is not an ideal procedure because it requires either the collection of blood at a laboratory or the repeated collection of small blood volumes through a pinprick.  Either one hurts.

Bioengineers at the University of Texas at Dallas developed a wearable diagnostic device to detect cortisol, glucose, and IL-6 in body sweat, eliminating any painful needle sticks.  Its transmissions vary, but if optimized, the device could replace the painful and inconvenient practice of sticking one’s finger to obtain a drop of blood for glucose testing, which many patients with diabetes must do several times per day. Although insulin pumps have been available for some time, these are invasive devices that must be worn at all times.

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!

Setton Named WashU BME Chair

Setton
Lori A. Setton, Ph.D.

Lori A. Setton, Ph.D., a major innovator in the field of tissue regeneration and repair and a member of the Penn Bioengineering Departmental Advisory Board, has been named chair of the Department of Biomedical Engineering at Washington University in St. Louis. Her appointment begins on August 1.

An alumna of Princeton (BSE) and Columbia (MS, Ph.D.) with degrees in mechanical engineering, Dr. Setton was on the faculty at Duke until 2015, when she moved to WashU. Over the last decade or so, she has coauthored nearly 150 peer-reviewed research papers in the field of biomedical engineering, establishing a sterling reputation as a scientist and researcher.

In addition to her distinguished career in research and academia, she is also the current president of BMES, where she has been a pioneer in fostering greater diversity within the field, both in instituting a partnership with the National Society for Black Engineers (NSBE) and as a mentor at Duke, where the introduction of a mentoring program to increase diversity among under-represented minorities has been particularly successful.

“We are thrilled that Lori was recognized with this significant leadership opportunity,” said David Meaney, Ph.D., chair of the Bioengineering Department at Penn. “As a key academic on our department advisory board, Lori’s incisive input on Penn Bioengineering has been invaluable as we grow and change as a department. I know she will be an outstanding leader for WashU.”

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!

Ducheyne Edits New Biomaterials Text

Ducheyne
Paul Ducheyne, Ph.D.

A Penn Bioengineering professor, Paul Ducheyne, Ph.D., is the editor-in-chief of the new second edition of Comprehensive Biomaterials II, released by Elsevier on June 1. The seven-volume collection, which Dr. Ducheyne edited along with faculty members from the University of California, Berkeley, Queensland University of Technology (Australia), University of Utah, and Johannes Gutenberg University Medical Center (Germany), collects articles written by experts in the field of biomaterials.

According to Elsevier, the articles “address the current status of nearly all biomaterials in the field, their strengths and weaknesses, their future prospects, appropriate analytical methods and testing, device applications and performance, emerging candidate materials as competitors and disruptive technologies, research and development, regulatory management, commercial aspects, and applications, including medical applications.”

In the preface to the collection, Dr. Ducheyne details how his team and Elsevier worked together to assure the continued high impact of the text by issuing it in both a print version and online via Elsevier’s Science Direct platform. He writes further, “It was the objective of the editorial team to compose the publication with chapters that would provide strategic insights for those working in diverse biomaterials applications, research and development, regulatory management, and industry.”

Bioengineering and BDM Go Together

by Joe Maggiore, Bioengineering ’19

BDM stage
Band Dance Music in performance

I’m a rising junior studying Bioengineering at Penn. I’m also the founder of a music group called Band Dance Music (BDM). The overall premise of the group is to take the same music that a DJ plays at a college party but to play it with an 11-piece live band. The idea for this group started before I got to Penn, but it was something that I was confident in pursuing despite all of the other time commitments during the school year.

Starting a band at Penn was definitely a challenge. There are already so many music groups on Penn’s campus that it’s very easy for a group that is just starting out to get drowned out by other more prominent groups. After really pushing marketing hard for auditions, it actually was pretty easy to find students who were interested in the idea behind the group. Interestingly, of the 11 members that are now in the group, nine of them are actually in the School of Engineering and Applied Science.

While bioengineering and band dance music seem like two totally disparate fields, I was actually able to bridge the gap between these areas while taking ENGR105 with Professor Rizk. At the end of this course, we are asked to create a graphical user interface (GUI) that combines the entire course’s material. This GUI is completely free form – it can be in any area of interest that you like.

Since for a while I’d been having trouble arranging music completely by ear, I thought this would be the perfect opportunity to create a GUI that would help me arrange music for the band. There is rarely free time to spare during the school year, so being able to work on a passionate project of mine while also being able to complete my course work was a win-win situation. The GUI definitely took me longer than expected to create since it involved having to process electronic music into parts that would be easier to arrange, but I eventually was able to finish the interface. It featured a tap metronome, a filtering system, and a visual music player so I could streamline the music writing process. Below is a pictures of the GUI I created.

BDM is always looking for more interesting people to join who have a passion for this unique concept for a band. If any bioengineers reading out there are interested, feel free to reach out to me – I’d love to talk more about it. Thanks for reading!