Several Illinois researchers are joining forces with scientists from the Mayo Clinic and Georgetown University on an expansive project targeting improved treatment for glioblastoma (GBM), the most aggressive form of brain cancer. The team, led by Brendan Harley, professor of chemical and biomolecular engineering, recently received a $3M grant from the National Cancer Institute (NCI) for their research that will unite the cell biology, bioengineering, and chemistry behind cancer drug development.
Glioblastoma is historically difficult to treat, with only a 25% survival rate over five years. When a cancer patient is diagnosed with GBM, they will most likely be undergoing surgery to remove the tumor – made significantly more difficult due to its sensitive location.
“Glioblastoma patients tend to have tumor re-occurrences within six to seven months of the surgery, and it’s within centimeters of the tumor margin,” Harley said. “It’s caused by the cancerous cells that could not be removed. This issue is what got our team really interested in how we can develop better therapeutic treatments.”
Harley, also a Cancer Center at Illinois Research Program Theme leader, is an expert in building tissue microenvironments, using bioengineering techniques to re-create the brain tissue. His lab is partnering with the Mayo Clinic and Rebecca Riggins, associate professor of oncology at Georgetown, to provide cell lines engineered to be resistant to temozolomide (TMZ), the primary chemotherapy used to treat GBM today.
Brendan Harley (left) and Paul Hergenorther (right).
Patient-derived cell lines, provided by Dr. Jann Sarkaria of Mayo Clinic who is another investigator on this project, provide another key element of the work. They are developing a biomaterial that simulates the vascular environment in the brain in order to understand how the tumor microenvironment can promote GBM cell resistance to drugs.
“When you treat a patient with TMZ, it causes damage to the DNA in the cancerous cells, causing them to die. However, these cells are able to avoid this damage in a number of ways, but a primary way is through MGMT [a DNA repair enzyme],” Harley said. “TMZ induces a mutation to the cancerous cell’s DNA to destroy it, but MGMT can reverse that.”
“So if a patient is MGMT-positive, they are more likely to be resistant to TMZ. Unfortunately, more than 60% of GBM patients are MGMT-positive, so the current frontline drug is given to GBM patients who have the primary resistance to the treatment living in their bodies,” Harley said.
Harley and his team have shown that the brain vasculature mimics they have developed provide new insight into MGMT resistance. If you are MGMT-negative, you have a two-year survival rate of 50%, but if you are MGM- positive, you only have a two-year survival rate of 15%.
During a separate project, Harley and Paul Hergenrother, professor of chemistry and the CCIL’s Deputy Director, realized that Hergenrother’s expertise in cancer therapeutics could aid the team in addressing MGMT.
“Since we knew the high level of resistance because of MGMT, my lab thought that we could design a compound that applies another mutation to the DNA that would not get removed, as well as something that gets into the brain more efficiently,” Hergenrother said. “The Harley lab will develop more predictive models, which will help us to evaluate the success of the cancer agents we create at a more rapid pace.”
The research team will explore how they can create a mutated version of TMZ that MGMT cannot remove, allowing for this new version of TMZ to successfully destroy cancerous cells. This grant is a part of the NCI’s Cancer Tissue Engineering Collaborative which will support the team’s efforts to better understand the physiological processes driving cancer progression and drug resistance.
“This program is committed to supporting research groups that are pushing the boundaries of tissue engineering technologies for cancer,” Harley said. “It connects us to both collaboration opportunities as well as what challenges our colleagues are facing so that we can work together to address them.”
Harley is the Robert W. Schaefer Professor of Chemical and Biomolecular Engineering and a research theme leader in the Carl R. Woese Institute for Genomic Biology (IGB). Hergenrother is the Kenneth L. Rinehart Jr. Endowed Chair in Natural Products Chemistry, a research theme leader in IGB, and the Director of the NIH Chemistry-Biology Interface Training Program.
By: Jordan Goebig, Communications Coordinator, Cancer Center at Illinois
Congratulations to Chemical and Biomolecular Engineering PhD students who have been selected to receive fellowships from the National Science Foundation Graduate Research Fellowship Program. They include Paola Baldaguez Medina, Vasiliki “Aliki” Kolliopoulos, and Chris Torres.
The NSF program recognizes and supports individuals early in their graduate training in science, technology, engineering, and mathematics fields. The aim is to help ensure the vitality and diversity of the scientific and engineering workforce in the U.S. The program provides three years of support for students who have demonstrated their potential for significant research achievements in STEM or STEM education.
Baldaguez Medina completed her undergraduate education at the University of Puerto Rico at Mayagüez in 2019. While there, she conducted research in separation processes with Professor Hernández-Maldonado and spectroscopy with Professor Hernández-Rivera. She also had internships at the University of Minnesota through the NSF Research Experiences for Undergraduates (REU) program working on block-copolymers, and at the University of Florida with Professor Rinaldi on rheology studies.
A member of Assistant Professor Xiao Su’s research group at the University of Illinois, her work focuses on developing water remediation techniques via electrochemical mediated systems for the removal of anthropogenic organic contaminants of concern. She uses redox-polymers electrodes for pollutant binding through electrosorption. Developing an electrochemical separation method could impact society in numerous ways by providing energy effective and modular technologies for water purification, Baldaguez Medina said.
Kolliopoulos is a member of Professor Brendan Harley’s lab, which has been developing advances in tissue engineering. Craniofacial bone defects are common in the context of congenital, traumatic, and post-oncologic conditions. Such bone defects are often large in size and heal poorly, motivating regenerative medicine efforts. A particular barrier to regenerative healing is the significant immune and inflammatory response post injury which can inhibit cell recruitment, vascular remodeling, and new tissue biosynthesis. The Harley lab is developing a class of mineralized collagen biomaterials capable of meeting a wide range of design requirements for successful deployment into CMF bone defects, notably the ability to conformally fit complex defect geometries and support stem cell osteogenesis.
Kolliopoulos said she aims to understand the effect of scaffold biophysical properties (microstructure, stiffness, alignment, mineral morphology) on the recruitment and subsequent activation status of macrophages. Her ultimate goal is to demonstrate biomaterials capable of modulating the kinetics of the macrophage response post injury as a means to accelerate implant integration and subsequent bone regeneration. She completed her undergraduate studies at The Ohio State University. In 2018, while working in the Carlos Castro Lab, she received an honorable mention for the NSF GRFP for her work on DNA Origami.
Torres is a member of Associate Professor David Flaherty’s research group. He studies the catalytic role of solid-liquid interfaces and extended solvent networks for liquid-phase oxidation reactions. His research goal is to create design rules for catalysts which reduce the environmental impact of chemical industries. He completed his undergraduate education at the University of New Mexico.
Several research images from Chemical and Biomolecular Engineering faculty are currently on display at the National Institutes of Health.
The exhibit was organized by the Carl R. Woese Institute for Genomic Biology and includes images from the labs of Professors Hyunjoon Kong, Brendan Harley, and Huimin Zhao. All three are researchers affiliated with IGB.
The IGB’s Art of Science program is a celebration of common ground between science and art. Each exhibit comprises images from IGB’s research portfolio, captured in its core facilities, and enhanced to highlight the beauty and fascination encountered daily in scientific endeavors. Art of Science images have been displayed at O’Hare International Airport in Chicago, at the Illinois State Capitol in Springfield, The Rayburn House Office Building in Washington, DC, the German Center for Innovation in NYC, and Abbott Diagnostics, among other locations.
The images can be found in the hallway just outside the library in the NIH Clinical Center (Building 10), down the hall from the Masur Auditorium in Betheseda, MD.
Congratulations to ChBE undergraduate Nicole Jugovich who was chosen for the Lisle Abbott Rose Award from the University of Illinois College of Engineering. The award is given to a student who most nearly approaches the ideal of technical excellence combined with cultural breadth, depth, and sensitivity.
Through the Illinois Scholars Undergraduate Research program, Nicole has been a part of two research teams. As a sophomore, she worked with Assistant Professor Ying Diao’s group and this year she has been a part of Professor Brendan Harley’s lab. In Dr. Diao’s lab, she worked on optimizing a dropwise fabrication process for synthesizing organic semiconductor crystals. In Dr. Harley’s lab, she investigates hydrogel systems which will be used to create a complex, 3D cell-laden model to study brain cancer cells.
The undergraduate from Western Springs said her interest in engineering grew out of an “Introduce a Girl to Engineering” day at Argonne National Laboratory in seventh grade. At that event she met a nuclear engineer who spoke about her experience as a woman in engineering and the potential applications of clean energy.
“Alongside her scholarly discussion, her sense of humor changed my perception of the ‘stereotypical’ engineer. Meeting so many intelligent and independent female engineers truly inspired me and sparked my interest in pursuing a STEM field,” Jugovich said.
She continued to challenge herself with advanced math and science coursework throughout high school at Benet Academy in Lisle and sought out more STEM-related opportunities, including a summer engineering camp at the U of I.
At Illinois she has been a member of the Society of Women Engineers, where she serves as the special events coordinator after a year as the secretary of the organization’s information and marketing committee. She is also a group leader for the Engineering Ambassador Program, which involves organizing and presenting science topics to students in grades 3-12 to spark their interest in engineering.
Nicole has a passion for bringing together diverse groups of people to solve problems. As the daughter of a Lebanese immigrant, Jugovich has traveled to Israel as part of Passages, a program for Christian college students. There she heard lectures from Jewish, Muslim, and Christian leaders on the Israeli-Palestinian conflict, expanding her broad global views. This summer she will travel to China as part of the Hoeft Technology & Management Program, a partnership between the College of Engineering and the Gies College of Business. Jugovich plans to work in industry at the intersection of business and engineering.
“Not only does the T&M program challenge students with rigorous coursework, but it also offers professional development workshops to build critical skills outside of the classroom. The unique lessons in mentorship, professional branding, and women in management have been especially helpful in my development as a rising professional,” she said.
The American Institute for Medical and Biological Engineering (AIMBE) has announced the pending induction of Dr. Brendan Harley, Professor of Chemical and Biomolecular Engineering, to its College of Fellows.
Election to the AIMBE College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer. It is comprised of the top two percent of medical and biological engineers. Membership honors those who have made outstanding contributions to engineering and medicine research, practice, or education and to the pioneering of new and developing fields of technology, making major advancements in traditional fields of medical and biological engineering, or developing/implementing innovative approaches to bioengineering education.
Dr. Harley was elected by peers and members of the college of fellows for “innovative and translational contributions to instructive and spatially graded biomaterials for regenerative medicine and for engineering dynamic cell-material interactions.”
He joined the Illinois faculty in 2008 and is a Professor and Robert W. Schaefer Faculty Scholar in the Department of Chemical and Biomolecular Engineering. He is also the leader of the Regenerative Biology and Tissue Engineering research theme at the Carl R. Woese Institute for Genomic Biology. He received his SB from Harvard University in 2000 and SM/ScD from MIT in 2002 and 2006.
At Illinois, Dr. Harley has focused his efforts on developing biomaterials that replicate the dynamic, spatially-patterned, and heterogeneous microenvironment found in the tissues and organs of our body. He and members of his lab use this approach to generate insight regarding the design of biomaterials for craniomaxillofacial and musculoskeletal tissue regeneration, hematopoietic stem cell engineering, as 3D models of the glioblastoma tumor microenvironment in the brain, and to replicate dynamic tissues such as the endometrium.
A formal induction ceremony was held during the AIMBE Annual Meeting at the National Academy of Sciences in Washington, DC on March 25, 2019. Dr. Harley was inducted along with 156 colleagues who make up the AIMBE College of Fellows Class of 2019.
While most AIMBE Fellows hail from the United States, the College of Fellows has inducted Fellows representing 30 countries. AIMBE Fellows are employed in academia, industry, clinical practice and government. They are among the most distinguished medical and biological engineers including two Nobel Prize laureates, 17 Fellows having received the Presidential Medal of Science and/or Technology and Innovation, and 158 also inducted to the National Academy of Engineering, 72 inducted to the National Academy of Medicine and 31 inducted to the National Academy of Sciences.
Congratulations to Jee-Wei Emily Chen, Chemical and Biomolecular Engineering graduate student in Professor Brendan Harley’s lab. Her image, “A Rising Moon Above the Mountain” was named winner of the School of Chemical Sciences’ 2018 Science Image Challenge.
The annual research image competition is sponsored by the School of Chemical Sciences and open to graduate and undergraduate students, postdoctoral associates/fellows, and staff members, excluding faculty members.
“Rising Moon Above the Mountain”
Description: This is a Scanning Electron Microscope (SEM) image of gelatin hydrogel added with false color composite with a glioblastoma brain tumor microshperoid environmental electron scanning microscope (ESEM) image. The tumor mimetic microspheroid embedded in the brain-mimetic hydrogel will allow us to visualize tumor therapeutic responses. Acknowledgement: SEM and ESEM image was taken at the Beckman Institute with assistance from Cate Wallace.
Students, faculty, and staff are invited to attend the SCS VizLab’s open house to celebrate the winner and finalists.
SCS VizLab Open House
151 Noyes Lab
2-4 p.m. Tuesday, Dec. 11
2:30 p.m. awards presentation
Refreshments will be provided.
In addition to Chen’s winning image, four finalists were named.
“Fire and Ice,” Marley Dewey, Harley Lab
Description: An environmental scanning electron microscope image of a poly(lactic acid) 3D print (blue) within a porous mineralized collagen scaffold (red). 3D prints are used to reinforce the soft mineralized collagen scaffold, which is used for bone regeneration of large missing bone defects in the skull and jaw.
“Feathers of the Ocean,” Prapti Kafle, Diao Lab
Description: Presented is a cross-polarized microscopy image of nanothin films of an anti-cancer drug ellipticine on edible polymer-pullulan. The film, produced by solution shearing of the drug solution under highly non-equilibrium conditions, embraces an elegant morphology with oriented needles and spherulites, that resembles feathers of a bird, camouflaging in the ocean.
“Molecular Machinery,” Matthew Chan, Shukla Lab
Description: Proteins are intricate molecular machines. Shown here, the serotonin transporter undergoes conformational changes to transport serotonin and ions across the membrane. Using computational simulations, we can visualize the complex dynamics to understand of how these molecular machines can be regulated. Image was based on simulation results and drawn in Illustrator.
“Molecular Dynamics of Cytochrome P450 with Endogenous Inhibitor Virodhamine,” Andres Arango, Tajkhorshid Lab, Center for Biophysics and Quantitative Biology
Description: Cytochrome P450s (CYPs) are responsible for the metabolism of many exogenous and endogenous biomolecules. This image depicts the molecular dynamics simulations virodhamine, an endogenous inhibitor of CYP2J2, the predominant CYP in heart tissue.
Dr. Brendan A. Harley has been honored with the Campus Award for Excellence in Undergraduate Teaching.
Harley, Robert W. Schaefer Faculty Scholar and associate professor, was chosen for his development of an innovative course on tissue engineering that introduces undergraduates to cutting-edge research in the biosciences. He supplements traditional lectures by selecting current journal articles that show students how to apply the knowledge from the lectures. He also is committed to the active recruitment and retention of underrepresented students, specifically women, in STEM disciplines.
The award recognizes sustained excellence in and innovative approaches to undergraduate teaching and contributions beyond classroom instruction that have an overall positive impact on undergraduate student learning. Honorees are represented in three employee categories: faculty, specialized faculty and teaching assistants. Winners were honored at a banquet this spring at the Beckman Institute for Advanced Science and Technology.
Congratulations to Chemical and Biomolecular Engineering students who have been awarded National Science Foundation Graduate Research Fellowships!
Launched in 1952, the NSF Graduate Research Fellowship program is the nation’s oldest and largest fellowship program for graduate students. It is also one of the most prestigious.
This year Danielle Harrier, ChBE PhD student with Dr. Damien Guironnet’s research group, was awarded a fellowship. Two members of Dr. Brendan Harley’s lab—ChBE senior Elijah Karvelis and MatSE grad student Marley Dewey—were awarded fellowships. Kevin Cheng, a Biophysics graduate student and member of Dr. Diwakar Shukla’s lab, also won the fellowship.
Harrier’s research with Assistant Professor Guironnet focuses on the development of a strategy to synthesize biodegradable polymer latex by emulsion ring opening polymerization.
“The technical challenge of this approach is to perform the water sensitive polymerization in an aqueous media. Therefore, the innovative aspect of my strategy is that I will utilize microfluidics techniques to encapsulate the catalyst in a hydrophobic nanoreactor and thus protect it from water,” she said.
Harrier completed her undergraduate studies at the University of New Mexico and began the PhD program in Chemical Engineering in Fall 2017.
“The research at U of I is at the forefront of understanding and solving current global issues, and I am excited to add to the breadth and depth of research being done by my PI, Professor Guironnet, by furthering research in sustainable polymers,” she said.
Elijah Karvelis graduates this May and plans to pursue a PhD. He is currently deciding between three schools.
His project in the Harley lab has been on developing biomaterial platforms for studying brain cancer, specifically leveraging microfluidics to look at invasion of cancerous cells.
The NSF awarded honorable mentions to ChBE graduate students Isamar Pastrana-Otero (Kraft Lab), Bijal Patel (Diao Lab) and Whitney Sinclair (Kenis Group).
On the battlefield, soldiers usually wear protective gear that covers most of their bodies, but in many cases the Kevlar helmets that soldiers wear cannot fully protect the face, head, and neck. A 2013 article in the journal Military Medicine reported on the increase in combat-related head, face, and neck injuries among service personnel wearing combat body armor.
With funding from the U.S. Army, researchers at the University of Illinois are looking for ways to repair complicated skull injuries with biomaterials—substances that can interact with or guide the body’s natural healing processes—instead of using artificial materials like titanium plates or grafting bone from other areas onto the head.
“The defects of the skull typically in battle injuries are very strange in shape, so we want to be able to design a scaffold or composite that can fit that exact shape for them and then it would regenerate their own bone,” said Marley Dewey, a doctoral student working in the lab of Brendan Harley, an associate professor of chemical and biomolecular engineering.
“These severe craniomaxillofacial (CMF) injuries present a series of unmet clinical challenges to improved healing,” Harley said. “And while tissue engineering approaches suggest the potential to improve healing, we must first address a series of bottlenecks. Implants must balance very real considerations regarding strength and load bearing, the need to fit complex defects unique to each patient, and biotransport of nutrients during healing.”
According to Harley, the project seeks to pioneer approaches to integrate a bioactive collagen biomaterial that includes micro-scale porosity with a strong reinforcement frame generated via 3D-printing with macro-scale porosity.
“Such composites are common in other areas of engineering, such as reinforced concrete,” said Harley, “but not yet in tissue engineering, presenting us with some unique opportunities to advance our field.”
Dewey and her colleague Aleczandria Tiffany, also a Ph.D. candidate, are using mineralized collagen to regenerate bone. The tools in the Beckman Institute’s Microscopy Suite help them see if they are getting the desired results.
Dewey examines how 3D-printed biomaterials can be used to reinforce the mineralized collagen scaffold, which isn’t as strong as regular bone. The goal is to create a composite composed of biodegradable materials that break down over time after bone cells have started to proliferate. Deciding on the proper amount of scaffolding material can also be tricky. Dewey uses the environmental scanning electron microscope (ESEM) and the micro x-ray computed tomography (microCT) system in Beckman’s Microscopy Suite to examine cellular response on the composites.
“I am looking for changes in structure and mineralization, but also to see that the 3D-printed materials are fully integrated into the mineralized collagen biomaterial, because gaps between them wouldn’t be ideal,” Dewey said.
“I also use microCT to see what the mineral content is. We have a program that a previous lab member developed using the microCT image files so you can quantify where the mineral is and how much is present.”
In addition, she uses the ESEM to examine the integration of anti-inflammatory agents incorporated into the collagen to combat bacterial infections and inflammatory responses that could be detrimental to soldiers experiencing a blast injury to the jaw on a battlefield, where it’s likely to be unhygienic.
Tiffany examines how incorporating growth factors—such as vascular endothelial growth factor and minerals such as zinc—work in helping an individual’s own bone grow within the scaffold.
“The scaffold is really porous,” Tiffany said. “Ideally the patient’s stem cells, already present at the wound site after injury, would migrate into it. So while Marley wants to add mechanical support, I want to add the growth factors so that those stem cells can be recruited into the material to accelerate bone regeneration.”
Zinc is incorporated into the scaffolds to promote mineralization and induce differentiation of stem cells. Using the ESEM allows Tiffany to see how zinc affects the microstructure within the scaffolds.
“Originally, I saw that when I added zinc there were no negative effects on overall pore structure, but then I could see that there was a definite difference in mineral microstructures with the addition of zinc,” Tiffany said. “We usually see ‘classic’ brushite plates, but with the addition of the zinc it’s very different. So I’ve added different concentrations of zinc to see how the mineral deposits change.”
These differences in microstructure may alter how stem cells generating bone interact with the scaffold. A cell’s microenvironment dictates its behavior, and this is something Tiffany hopes to explore more fully.
“Ideally I would want to see a cellular response to the zinc,” Tiffany said. “Hopefully with the addition of zinc we would see an increase in differentiation into osteoblasts and the expression of bone-related genes.” She hopes to use critical point drying at Beckman to examine how the cell’s morphology changes in her various scaffold types.
Both Dewey and Tiffany appreciate the one-on-one support from the Microscopy Suite staff.
“I had no knowledge of microCT or ESEM before I came here,” Dewey said. “Because my background was in chemical engineering, we didn’t use any microscopy tools. I didn’t even know what ESEM was.”
“It’s obvious that both Marley and Alec are power hitters,” said Scott Robinson, manager of the Microscopy Suite. “They are really engaged in their work and doing a great job; and we’re very happy to have them using the suite.”
Dewey thinks that the Microscopy Suite staff’s assistance has helped her produce great images useful in publications and presentations.
Tiffany, likewise, hadn’t had experience with the microscopes and credits Cate Wallace, Leilei Yin, and Robinson with providing their expertise to help the project along.
“We want our users to get the best possible images out of the various microscopes, and if some samples are tricky, making it hard to consistently pull up those killer images, we might check in on them more often,” said Robinson. “People working in bio and in biomaterials can face more difficulties in imaging their samples than straight materials people, and sometimes they can use more help. We have years of experience to offer them.”
“Now it’s at the point where Scott will come in and say ‘beautiful picture, you don’t need my help,’” Tiffany said. “But he still comes in almost every time I’m in there, just to tell me that the images are beautiful.”
By Maeve Reilly, Beckman Institute
Chemical and Biomolecular Engineering Professors David Flaherty and Brendan Harley have been named winners of the College of Engineering Dean’s Award for Excellence in Research. The award is given annually to a handful of engineering faculty in recognition of their research. Both will be honored at the college’s faculty awards ceremony on April 23.
Since they joined the department, Professors Harley and Flaherty have emerged as exceptional scientists and mentors, said Paul Kenis, William H. and Janet G. Lycan Professor and Department Head.
“It’s rewarding to see faculty recognized for their dedication to advancing science and leading and training research groups that are doing truly pioneering work. I expect they will continue to push the boundaries of their fields—Harley in biomaterials and Flaherty in heterogeneous catalysis,” Kenis said.
Flaherty, an assistant professor in the department, said he is inspired by the accomplishments of his research group and “thrilled to see the efforts of my students recognized in this way.”
The Flaherty Research Group develops new principles needed to design catalytic materials and systems for the sustainable production of consumer products and fuels.
“This difficult work is only possible because of the many forms of support we receive from our department and from the campus. Interactions with exceptional colleagues and the use of outstanding facilities are a few of the ways in which Illinois cultivates excellent research. I am honored for our group to be acknowledged along with the many brilliant engineers at Illinois,” he said.
Flaherty, who joined the department in 2012, holds a BS from University of California, Berkeley and a PhD from the University of Texas at Austin.
Harley said it was a humbling to receive such an award.
“There are amazing faculty doing innovative, meaningful research across this campus. To be recognized in this manner is a tribute to the outstanding trainees in my group who everyday work to make science bigger, more rigorous, and more inclusive,” said Harley, associate professor and Robert W. Schaefer Faculty Scholar. “It is also a reflection of my colleagues, collaborators, as well as the facilities and support staff on this campus who make our work possible.”
The Harley Research Group explores “how we can design biomaterials that can be implanted into the body to facilitate regeneration. But we also are developing biomaterials to examine biological processes outside of the body such as disease development and treatment.”
“Our challenge is to develop materials that mimic the complex, heterogeneous environment within the tissues and organs of our body,” Harley said. “We are excited about the potential of our work, such as finding new ways to predict drug resistance and patient-to-patient variability in cancer as well as to implants to regenerate complex musculoskeletal injuries such as composite (hard and soft tissue) craniofacial defects experienced by warfighters after high-energy impacts.”
Harley joined the department in 2008. He holds an SB degree from Harvard University and an SM/ScD from MIT.