Bioengineering Round-Up (December 2019)

by Sophie Burkholder

Positive results in first-in-U.S. trial of CRISPR-edited immune cells

3D render of the CRISPR-Cas9 genome editing system

Genetically editing a cancer patient’s immune cells using CRISPR/Cas9 technology, then infusing those cells back into the patient appears safe and feasible based on early data from the first-ever clinical trial to test the approach in humans in the United States. Researchers from the Abramson Cancer Center have infused three participants in the trial thus far—two with multiple myeloma and one with sarcoma—and have observed the edited T cells expand and bind to their tumor target with no serious side effects related to the investigational approach. Penn is conducting the ongoing study in cooperation with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics.

“This trial is primarily concerned with three questions: Can we edit T cells in this specific way? Are the resulting T cells functional? And are these cells safe to infuse into a patient? This early data suggests that the answer to all three questions may be yes,” says the study’s principal investigator Edward A. Stadtmauer, section chief of Hematologic Malignancies at Penn. Stadtmauer will present the findings next month at the 61st American Society of Hematology Annual Meeting and Exposition.

Read the rest of the story on Penn Today.

Tulane researchers join NIH HEAL initiative for research into opioid crisis

A Tulane University professor and researcher of biomedical engineering will join fellow researchers from over 40 other institutions in the National Institute of Health’s Help to End Addiction Long-Term (HEAL) Initiative. Of the $945 million that make up the project, Michael J. Moore, Ph.D. will receive a share of $1.2 million to advance research in modeling human pain through computer chips, with the help of fellow Tulane researchers Jeffrey Tasker, Ph.D., and James Zadina, Ph.D., each with backgrounds in neuroscience.

Because of the opioid epidemic sweeping the nation, Moore notes that there’s a rapid search going on to develop non-addictive painkiller options. However, he also sees a gap in adequate models to test those new drugs before human clinical trials are allowed to take place. Here is where he hopes to step in and bring some innovation to the field, by integrating living human cells into a computer chip for modeling pain mechanisms. Through his research, Moore wants to better understand not only how some drugs can induce pain, but also how patients can grow tolerant to some drugs over time. If successful, Moore’s work will lead to a more rapid and less expensive screening option for experimental drug advancements.

New machine learning-assisted microscope yields improved diagnostics

Researchers at Duke University recently developed a microscope that uses machine learning to adapt its lighting angles, colors, and patterns for diagnostic tests as needed. Most microscopes have lighting tailored to human vision, with an equal distribution of light that’s optimized for human eyes. But by prioritizing the computer’s vision in this new microscope, researchers enable it to see aspects of samples that humans simply can’t, allowing for a more accurate and efficient diagnostic approach.

Led by Roarke W. Horstmeyer, Ph.D., the computer-assisted microscope will diffuse light through a bowl-shaped source, allowing for a much wider range of illumination angles than traditional microscopes. With the help of convolutional neural networks — a special kind of machine learning algorithm — Horstmeyer and his team were able to tailor the microscope to accurately diagnose malaria in red blood cell samples. Where human physicians typically perform similar diagnostics with a rate of 75 percent accuracy, this new microscope can do the same work with 90 percent accuracy, making the diagnostic process for many diseases much more efficient.

Case Western Reserve University researchers create first-ever holographic map of brain

A Case Western Reserve University team of researchers recently spearheaded a project in creating an interactive holographic mapping system of the human brain. The design, which is believed to be the first of its kind, involves the use of the Microsoft HoloLens mixed reality platform. Lead researcher Cameron McIntyre, Ph.D., sees this mapping system as a better way of creating holographic navigational routes for deep brain stimulation. Recent beta tests with the map by clinicians give McIntyre hope that the holographic representation will help them better understand some of the uncertainties behind targeted brain surgeries.

More than merely providing a useful tool, McIntyre’s project also brings together decades’ worth of neurological data that has not yet been seriously studied together in one system. The three-dimensional atlas, called “HoloDBS” by his lab, provides a way of finally seeing the way all of existing neuro-anatomical data relates to each other, allowing clinicians who use the tool to better understand the brain on both an analytical and visual basis.

Implantable cancer traps reduce biopsy incidence and improve diagnostic

Biopsies are one of the most common procedures used for cancer diagnostics, involving a painful and invasive surgery. Researchers at the University of Michigan are trying to change that. Lonnie Shea, Ph.D., a professor of biomedical engineering at the university, worked with his lab to develop implants with the ability to attract any cancer cells within the body. The implant can be inserted through a scaffold placed under the patient’s skin, making it a more ideal option than biopsy for inaccessible organs like lungs.

The lab’s latest work on the project, published in Cancer Research, details its ability to capture metastatic breast cancer cells in vivo. Instead of needing to take biopsies from areas deeper within the body, the implant allows for a much simpler surgical procedure, as biopsies can be taken from the implant itself. Beyond its initial diagnostic advantages, the implant also has the ability to attract immune cells with tumor cells. By studying both types of cells, the implant can give information about the current state of cancer in a patient’s body and about how it might progress. Finally, by attracting tumor and immune cells, the implant has the ability to draw them away from the area of concern, acting in some ways as a treatment for cancer itself.

People and Places

Cesar de la Fuente-Nunez, PhD

The Philadelphia Inquirer recently published an article detailing the research of Penn’s Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering, Cesar de la Fuente, Ph.D. In response to a growing level of worldwide deaths due to antibiotic-resistant bacteria, de la Fuente and his lab use synthetic biology, computation, and artificial intelligence to test hundreds of millions of variations in bacteria-killing proteins in the same experiment. Through his research, de la Fuente opens the door to new ways of finding and testing future antibiotics that might be the only viable options in a world with an increasing level of drug-resistant bacteria

Emily Eastburn, a Ph.D. candidate in Bioengineering at Penn and a member of the Boerckel lab of the McKay Orthopaedic Research Laboratory, recently won the Ashton fellowship. The Ashton fellowship is an award for postdoctoral students in any field of engineering that are under the age of 25, third-generation American citizens, and residents of either Pennsylvania or New Jersey. A new member of the Boerckel lab, having joined earlier this fall, Eastburn will have the opportunity to conduct research throughout her Ph.D. program in the developmental mechanobiology and regeneration that the Boerckel lab focuses on.

BE Seminar Series: January 9th with Ning Jenny Jiang, Ph.D.

Our first seminar in our Penn Bioengineering seminar series will happen shortly after the winter break, so be sure to mark your calendars now!

Jenny Jiang, Ph.D.

Speaker: Ning Jenny Jiang, Ph.D.
Associate Professor of Biomedical Engineering
University of Texas at Austin

Date: Thursday, January 9, 2020
Time: 12:00-1:00 pm
Location: Room 337, Towne Building

 

 

 

Title: “High-throughput T Cell Repertoire Profiling Enabled Systems Immunology and Immune Engineering”

 

Abstract:

T cells are important to the initiation, prevention, and cure of many diseases. For example, various T cells based cancer immunotherapies have been quite effective in treating several types of cancers. However, a significant fraction of patients do not respond. A comprehensive understanding of the complexity of the T cells repertoire in health and diseases not only provide underlying mechanisms but also new therapeutic targets. In the past several years, we have developed several tools to profile the T cell repertoire from T cell receptor diversity to T cell receptor affinity to multi-dimensional profiling of single T cells in high-throughput. In this talk, I will first introduce these tools and then give examples on how we use them to answer some of the fundamental questions in systems immunology, which in turn help us design new approaches in immune engineering.

Bio:

Dr. Jenny Jiang is an associate professor in the Department of Biomedical Engineering at the University of Texas at Austin. She obtained her Ph.D. from Georgia Institute of Technology and did her postdoc training at Stanford University. Her lab focuses on systems immunology by developing technologies that enable high-throughput, high-content, single cell profiling of T cells in health and disease. Dr. Jiang is a recipient of the prestigious NIH Pathway to Independence Award (K99/R00), Cancer Prevention and Research Institute of Texas, Damon Runyon-Rachleff Innovator Award, NSF CAREER Award, a Chan Zuckerberg Initiative Ben Barres Early Career Acceleration award, and was recently selected as one of National Academy of Medicine 2019 Emerging Leaders in Health and Medicine Scholars.

Cesar de la Fuente ‘Trends in Immunology’ Literature Review

by Sophie Burkholder

 

Cesar de la Fuente, PhD

Cesar de la Fuente, Ph.D., a Presidential Assistant Professor in Psychiatry, Microbiology, and Bioengineering at Penn, recently published a literature review in Trends in Immunology entitled, “Emerging Frontiers in Microbiome Engineering.” The microbiome, in simple terms, consists of the genetic material of microorganisms in the gut, including bacteria, fungi, protozoa,  viruses, and oral, vaginal, and skin microbiomes. Each human has a unique microbiome that depends both on predetermined factors like exposure to microorganisms within a mother’s birth canal or breastmilk in early life as well as environmental factors and diet in later life. The health of someone’s microbiome is extremely important, as an unhealthy microbiome with an imbalance of symbiotic and pathogenic microbes can make a person more susceptible to various diseases. The most common diseases or disorders associated with a problematic microbiome are rather far-reaching, including some of the most afflicting diseases of today like inflammatory bowel disease, diabetes, obesity, cardiovascular diseases, and neurological disorders.

In his recent literature review, de la Fuente provides an overview of microbiome engineering, and what the future might hold for the field. He defines microbiome engineering initially as a way of studying the “contribution of individual microbes and generating potential therapies against metabolic, inflammatory, and immunological diseases.” Currently, most treatments for issues with the microbiome are broad solutions like dietary adjustments to include more probiotics, antibiotics, or prebiotics, while more serious cases may require a fecal microbiota transplant. While these therapies may work for some patients, de la Fuente emphasizes the need for greater specificity in treatment targets and a need for precision in reprogramming existing microbial communities as an alternative to transplants.

De la Fuente highlights the current methods and tools in microbiome engineering such as the use of bacteriocins and bacteriophages to knock out specific bacteria within the microbiome. However, there are very few bacteriocins or bacteriophages commercially available on today’s market. Another common approach to microbiome engineering is in synthetic biology, or the use of “chassis” — a type of cell that maintains DNA constructs for different functions — to engineering interactions within the microbiome. De la Fuente continues his discussion of current methods by naming and describing several specific examples of these approaches, particularly in relation to synthetic biology options before moving on to examine future directions for these methods.

Before bringing up potential new frontiers for microbiome engineering, de la Fuente also outlines the way that microbiome engineering works in the first place, and dedicates sections of the review to the microbiome’s influence on its host’s immune system and how to engineer the microbiome to modulate that immune system. The main future methods for microbiome engineering that de la Fuente points out in his review include more precise regulation of gene expression through commensal organisms and the use of CRISPRi to find genes involved in bacterial maintenance. The conclusion of de la Fuente’s review brings up the notion of new personalized medicine or therapy for the microbiome that could come with further advances in the field. However, he also makes sure to bring up some still-outstanding questions about the human microbiome that require further research, most notably, what exactly makes a healthy human microbiome? Here’s hoping the research de la Fuente mentions can illuminate a path to the answer.

Penn Engineers Coax White Blood Cells to Crawl Upstream, Enabling Faster Route to Infections

When the immune system detects a foreign pathogen, a cascade of chemical signals call white blood cells to the scene. Neutrophils are the most common and abundant type of these cells and while they start accumulating at the site of an infection within minutes, they are essentially at the mercy of the circulatory system’s one-way flow of traffic to get them where they need to go.

Now, research from the University of Pennsylvania’s School of Engineering and Applied Science shows how these cells can be coaxed to fight the direction of blood flow, crawling upstream along the walls of veins and arteries.

The in vitro study suggested that this technique could get neutrophils to the sites of infections faster when they are restricted to the direction of blood flow.

Alexander Buffone and Daniel Hammer

Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor in the Department of Bioengineering, and Alexander Buffone, Jr., a research associate in his lab, led the research. Nicholas R. Anderson, a graduate student in the Hammer lab, also contributed to the study.

They published their findings in Biophysical Journal.

Read the full post on the Penn Engineering Blog.