The Center for Biomanufacturing Science and Technology brings together faculty at the University of Delaware that tackle a wide array of problems and fundamental challenges in areas ranging from: cell culture processes and bioreactors; high-end and scalable purification processes; product formulation and stability; drug delivery; manufacturing; and analytical technologies, instrumentation, and algorithms to support all of these areas. The Center supports cutting edge research facilities on campus, educational activities including seminars, workshops, and shortcourses, as well as industrial research consortia.
NEW WEAPON AGAINST BREAST CANCER
Light-triggered therapies work better together than separately against triple-negative breast cancer
Two University of Delaware researchers have developed a new approach to attack cancer, using two light-activated treatments that appear to be more effective together than when applied independently. More research is needed, but the findings point to promising new approaches against an especially challenging kind of cancer — triple negative breast cancer — which was the focus of their recent studies. Triple negative breast cancer is a particularly aggressive form of breast cancer that accounts for 10 to 20 percent of patients. It is called triple negative because the cancer cells do not have three biomolecules commonly found on other breast cancer cells – receptors for the hormones estrogen and progesterone and another receptor known as HER2. This means there are no targeted treatments for triple-negative breast cancer, so it is usually managed with surgery, radiation and/or chemotherapy. Each of these options has negative side effects with less than ideal patient outcomes. Now UD researchers Emily Day, assistant professor of biomedical engineering, and Joel Rosenthal, associate professor of chemistry and biochemistry, and their labs have shown that a combination of two minimally invasive therapies could give doctors a more powerful weapon against this cancer as well as others. Both treatments are activated by near-infrared wavelengths of laser light, but each accomplishes its mission differently. One — called photodynamic therapy (PDT) — uses light-sensitive agents called photosensitizers to produce a lethal form of oxygen (singlet oxygen) to accomplish a combustion-like destruction of the cancer cells. The other therapy — called photothermal therapy (PTT) — uses light-sensitive gold nanoshells that heat up when irradiated with light and can essentially ‘cook’ cancer cells to death.
RECOGNITION FOR BIOTECHNOLOGY INFLUENCER
Kelvin Lee receives Marvin J. Johnson Award in Microbial and Biochemical Technology
As the director of NIIMBL, the National Institute for Innovation in Manufacturing Biopharmaceuticals, Kelvin Lee is a changemaker in the biomanufacturing industry, which has the potential to save lives, improve national security, and increase economic development in the United States. For his impact in microbial and biochemical technology, Lee, Gore Professor of Chemical and Biomolecular Engineering at the University of Delaware, has received the 2019 Marvin J. Johnson Award in Microbial & Biochemical Technology from the American Chemical Society’s Division of Biochemical Technology. He will receive the award at the spring meeting of the American Chemical Society, to be held from March 31 to April 4, 2019. “Kelvin has the unique ability to combine scientific excellence with a level of vision and leadership quality to impact the broader biotechnology community,” said Wilfred Chen, Gore Professor of Chemical and Biomolecular Engineering at UD and the 2017 recipient of the Marvin J. Johnson Award. Lee joins Chen and two other UD colleagues who have received the Marvin J. Johnson Award — Abraham Lenhoff (2011) and Eleftherios Papoutsakis (1998). UD and the University of California at Berkeley are the only two universities to have four winners of the Marvin J. Johnson Award on their faculties.
Leadership and research excellence
With NIIMBL, a Manufacturing USA Institute headquartered in Newark, Delaware, Lee and the NIIMBL team lead a national consortium working to bring safe drugs to market faster and developing workforce training in the field of biopharmaceuticals.
A NEW WAY TO USE CRISPR
UD engineers develop methods to use CRISPR technology for conditional gene regulationA team of engineers at the University of Delaware has developed a method to use CRISPR/Cas9 technology to set off a cascade of activities in cells, a phenomenon known as conditional gene regulation. Their method, described in the journal Nature Chemical Biology, introduces a new functionality to CRISPR, one of today’s most-talked-about technologies. Gene editing with CRISPR technology has been called “one of the biggest science stories of the decade” for its applications to medicine, agriculture and much more. CRISPR allows scientists to precisely target and edit DNA within living cells, which could help them correct anomalies that cause inherited diseases. The first clinical trials in humans are underway in China. However, until now, scientists hadn’t figured out how to program their CRISPR systems to target DNA while integrating information from within the cells they were studying. At UD, Wilfred Chen, the Gore Professor of Chemical Engineering, and graduate student Ka-Hei Siu designed structures — dubbed toehold-gated gRNA (thgRNA)— for targeted gene regulation in E. coli bacteria.
OGUNNAIKE RECOGNIZED FOR CHEMICAL ENGINEERING EDUCATIONBabatunde Ogunnaike, the William L. Friend Chair of Chemical Engineering at the University of Delaware, received the Warren K. Lewis Award for Chemical Engineering Education in October at the American Institute of Chemical Engineers (AIChE) annual meeting. AIChE is the world’s leading organization for chemical engineering professionals, with more than 60,000 members from more than 110 countries. The Warren K. Lewis Award, given since 1963, is sponsored by ExxonMobil Research & Engineering Company. Ogunnaike was the dean of the College of Engineering from July 2011 until October 2018 and joined the UD faculty full-time in 2002. He previously worked in research and development for DuPont for 14 years. He has also taught classes at the University of Wisconsin-Madison, University of Lagos and African University of Science and Technology. Ogunnaike earned his doctoral degree in chemical engineering from the University of Wisconsin-Madison in 1981. In honor of Ogunnaike’s seven years of service as dean, the University established the Babatunde Ogunnaike Global Engineering Student Enrichment Fund, which is structured to provide financial assistance for students to engage in impactful global activities, such as an Engineers Without Borders service trip, a summer, semester, or winter session in a study abroad program, or international research in support of a new entrepreneurial venture.
GENE THERAPY FOR BLOOD DISORDERS
UD engineers develop particles to reach stem cells
Gene therapy holds a lot of promise in medicine. If we could safely alter our own DNA, we might eliminate diseases our ancestors passed down to us. Now, a team of University of Delaware researchers has demonstrated a major step forward in gene therapy by engineering microparticles that deliver gene-regulating material to hematopoietic stem and progenitor cells, which live deep in our bone marrow and direct the formation of blood cells. In a paper published in the journal Science Advances, Chen-Yuan Kao, a doctoral student in chemical engineering, and Eleftherios T. (Terry) Papoutsakis, Unidel Eugene du Pont Chair of Chemical and Biomolecular Engineering, describe how they used megakaryocytic microparticles, which circulate naturally in the blood stream, to deliver plasmid DNAs and small RNAs to hematopoietic stem cells. With more development, this technology could be useful in treatment for inherited blood disorders that affect thousands of Americans. These include, for example, sickle cell anemia, a disease that causes abnormally shaped red blood cells, and thalassemia, which disrupts the production of the blood protein hemoglobin.
EMILY DAY NAMED MANGONE YOUNG SCHOLAR
She also received the Rita Schaffer Young Investigator Award from the Biomedical Engineering Society
Emily Day, an assistant professor of biomedical engineering at the University of Delaware, has been selected by the University’s Francis Alison Society to receive the 2018 Gerard J. Mangone Young Scholars Award. The award recognizes promising and accomplished young faculty. The recipient is chosen by fellow faculty members who have received the Francis Alison Award, the University’s highest competitive faculty honor. In high school, Day was inspired by a science teacher who helped her appreciate the joy of learning something new and she now tries to pass that to her students at UD.
WILFRED CHEN AND DNA COMPUTERS
UD Engineering professor recognized for work in protein engineering, synthetic biology
Wilfred Chen joined UD in 2011 as the Gore Professor of Chemical Engineering. He was previously a Presidential Chair of Chemical Engineering at the University of California, Riverside. He earned his bachelor’s degree in chemical engineering at the University of California, Los Angeles, and his doctoral degree in chemical engineering from the California Institute of Technology. Two shelves in Chen’s office are lined with “Star Wars” movie memorabilia. Not long ago, the protein engineering research that takes place in his laboratory could have been the subject of science fiction, too. Chen develops technologies to modify proteins and DNAs in beneficial ways for applications that range from human health to sustainable energy. This includes novel uses of DNA computing and CRISPR Cas9, technologies of growing interest in synthetic biology. For example, Chen’s team has developed a technology to program strands of DNA into switches that turn proteins on and off — an innovation that could lead to the development of new cancer therapies and other drugs. In recognition of his contributions to the field, Chen will receive the 2018 American Institute of Chemical Engineers (AIChE) Food, Pharmaceutical and Bioengineering Division Award in Chemical Engineering at the 2018 AIChE Annual Meeting.
HITCHHIKERS HINDER MEDICATION SHELF LIFE
UD ingenuity sheds light on key biopharmaceutical manufacturing problem
Why some biopharmaceuticals have a longer shelf life than others is a problem that has baffled scientists and manufacturers alike. Even the same medication, produced by different manufacturers, can vary in its storage life. University of Delaware Professors Kelvin Lee and Abraham Lenhoff offer insight on one way this can happen in a special class of drugs called monoclonal antibodies, which comprise a large fraction of biopharmaceuticals. Traditional small molecule medicines, such as ibuprofen or aspirin, are manufactured using well-defined, discrete chemical reactions between various chemical compounds. Biopharmaceuticals, on the other hand, are much larger and more complex molecules that are manufactured by growing cells that produce a desired protein (often, an antibody) that is purified to create the medicine. Biopharmaceuticals can be used to treat cancers and autoimmune or inflammatory disorders, such as rheumatoid arthritis and Crohn’s disease. Adalimumab, for example, is a monoclonal antibody that blocks inflammation caused by rheumatoid arthritis by binding to the signaling protein that triggers the swelling.
PRASAD DHURJATI ELECTED AS A FELLOW OF THE ROYAL SOCIETY OF MEDICINE
Prasad Dhurjati has been invited to be an overseas fellow of the Royal Society of Medicine, established in England in 1805
Prasad Dhurjati, professor of chemical and biomolecular engineering with joint appointments in mathematical sciences and biological sciences, has accepted an invitation to be an overseas fellow of the Royal Society of Medicine. Dhurjati’s collaborative work with biologists in computer modeling has provided much insight into medical research including brain cancer, osteoporosis, autism and the human gut microbiome. He joined the UD faculty in 1982. The Royal Society of Medicine was established in England in 1805. Among its honorary members are Charles Darwin, Louis Pasteur and Sigmund Freud.
SHINING A LIGHT ON GENE REGULATION
UD engineers lay groundwork for cutting-edge cancer drugs
Cancer treatments—from radiation to surgery to chemotherapy—are designed to remove or kill cancerous cells, but healthy cells often become collateral damage in the process. What if you could use lasers to pinpoint the treatment area and deliver medicine to cancer cells only? A research team at the University of Delaware, led by Emily Day, an assistant professor of biomedical engineering, is laying the groundwork for a method to inhibit cancer-promoting genes in cancer cells while leaving healthy cells intact. In a new paper published in Nano Letters, the team reveals unprecedented insights into this promising method, which involves coating nanoparticles with gene-regulatory agents and then exposing them to a dose of laser light to unleash that material. Because the nanoparticles hold the gene regulatory agents inactive until their release is triggered on-demand with light, they have substantial potential to enable high precision cancer therapy while minimizing impact to non-irradiated healthy cells.
FACULTY SPOTLIGHT: APRIL KLOXINApril Kloxin, assistant professor of chemical and biomolecular engineering and materials science and engineering at the University of Delaware, is the ACS Division of Polymer Chemistry Researcher of the Month for May 2018. Her research group seeks to design dynamic materials, including novel biomaterials, and use them to understand and direct important biological signals in tissue regeneration and disease. Kloxin was also recently featured on the Susan G. Komen 3-Day Blog for her work addressing the issue of late recurrence for breast cancer survivors. In 2016, she received a Career Catalyst Research Award from the Susan G. Komen Roundation for this work. “My research group is working to develop materials that mimic the body tissues where breast cancer recurrence is likely to occur,” she said in the blog post. “Our team is trying to understand how the environment of these tissues causes dormant breast cancer cells to ‘wake up’, leading to recurrence.”
ENGINEERING’S EMILY DAY EARNS NSF CAREER AWARD
Developing nanoscale materials to outsmart cancerous tumors
Emily Day, an assistant professor of biomedical engineering at the University of Delaware, has received a National Science Foundation (NSF) Career award to engineer membrane-wrapped nanoparticles for targeted ribonucleic acid (RNA) delivery to breast cancer cells. The grant, which is expected to total $500,000, will start on May 1, 2018 and last until April 30, 2023. Day studies how nanoparticles, which measure about one-thousandth the width of a human hair, can be used in cancer treatment. For example, she is known for her previous research on the use of gold nanoparticles for heat-based treatment of cancer and for gene regulation of cancer. For this project, Day is making novel nanoparticles containing special ribonucleic acid (RNA) molecules.
PROGRAMMING DNA TO DELIVER CANCER DRUGS
Engineers control cellular proteins with biological computing
DNA has an important job—it tells your cells which proteins to make. Now, a research team at the University of Delaware has developed technology to program strands of DNA into switches that turn proteins on and off. UD’s Wilfred Chen Group describes their results in a paper published Monday, March 12 in the journal Nature Chemistry. This technology could lead to the development of new cancer therapies and other drugs.
MANUFACTURING USA HEADQUARTERS
Secretary of Commerce Penny Pritzker announces the National Institute for Innovation in Manufacturing Biopharmaceuticals.
Secretary of Commerce Penny Pritzker visited the University of Delaware today, where she announced a new institute to advance U.S. leadership in pharmaceutical manufacturing. The Newark-based National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) will be the 11th Manufacturing USA Institute. Biopharmaceuticals are prescription drugs made with living cells. Most drugs are chemistry-based and far easier to produce. The biopharmaceutical category includes vaccines, cancer drugs and drugs to treat autoimmune diseases, as well as emerging drugs for cell and gene therapies. The institute will focus on bringing safe drugs to market faster and on developing workforce training. The biopharmaceutical field has a negative unemployment rate, with more jobs available than there are qualified workers. A team of more than 150 companies, educational institutions, nonprofits and state governments will operate NIIMBL under a newly formed nonprofit. Expected total investment from all stakeholders totals $250 million, including $70 million of federal investment. The University of Delaware will handle administrative duties for the institute in partnership with the Commerce Department’s National Institute of Standards and Technology (NIST).
STOPPING CANCER RECURRENCE
Susan G. Komen Grant to Support Research on Breast Cancer Recurrence
Although early detection and better treatments have resulted in more women with breast cancer surviving past the five-year mark, 20 percent of disease-free patients will experience a recurrence anywhere from five to 25 years later at a metastatic site — most often in the bone marrow or the lungs. And their chances of surviving this secondary cancer are lower because it is often quite advanced before it is detected. “There’s a significant clinical need to understand the mechanism of late cancer recurrence to determine disease markers and improve treatment strategies,” says the University of Delaware’s April Kloxin. “It has been hypothesized that late recurrences originate from tumor cells that disseminate to these other tissues in the body where they become dormant and are later re-activated.”