Center for Targeted Therapeutics and Translational Nanomedicine (CT³N)

CT3N in the News

  • Seven Penn Researchers Receive NIH Director’s Awards [Michael Mitchell - New Innovator Award]

    Tuesday, October 2, 2018

    Michael Mitchell, PhD, the Skirkanich Assistant Professor of Innovation in Penn’s School of Engineering and Applied Science’s Department of Bioengineering, will also receive $2.4 million to further his lab’s work employing tools and concepts from cellular engineering, biomaterials science, and drug delivery to understand and therapeutically target complex biological barriers in the body. His lab applies their research findings — and the drug delivery technologies developed — to a range of human health applications, including cancer metastasis, immunotherapy, and gene editing. Among his research interests, Mitchell designs drug delivery technologies to engineer cells in the bone marrow and blood vessels as a way of gaining control over how and why cancer disseminates throughout the body, as well as to engineer immune cells for immunotherapy and vaccination. Grant ID: DP2-TR002776

  • The 2018 Penn Medicine Awards of Excellence Recipients for Research include: Stanley N. Cohen Biomedical Research Award to Roger A. Greenberg, MD, PhD, of the Department of Cancer Biology.

    Wednesday, September 12, 2018

  • Targeting Hard-to-Reach Domains with Nanogel Drug Carriers Abstract Video appears on Advanced Science News (featuring Vladimir Muzykantov's Lab)

    Tuesday, August 28, 2018

    The work focuses on a key feature of the vascular surface, caveolae. Caveolae play an important role in inflammatory diseases. In fact, Vlad’s group has found that anti-inflammatory drugs can get a boost in therapeutic activity against lung injury when they’re delivered specifically to caveolae (link). Caveolae may also act as gatekeepers for a process, transcytosis, that transports material in the blood to the space outside of the blood vessel. However, caveolae are characterized by a specific geometry: They’re shaped like small caves on the inner surface of the blood vessel. The entrances to the caves are 30-50 nanometer bottlenecks. We’ve previously found that the entry mouths of caveolae pose a problem when we try to deliver large drug payloads to caveolae with nanoparticles. The bottlenecks exclude particles as small as 100 nanometers from accessing caveolae. We’ve concurrently been working with our collaborators in the department of bioengineering to create nanoparticles with a high degree of mechanical flexibility. We found that our particles can stretch and compress under forces resembling those they might encounter in the bloodstream, even deforming to slip through pores an order of magnitude smaller than their diameter. We used antibodies to target these flexible particles to caveolae in the lungs and found that flexible particles as large as 300 nanometers are able to access the narrow 30-50 nanometer caveolae, whereas rigid particles of identical size cannot. While we haven’t yet completed work showing that the flexible nanoparticles can pack a larger therapeutic punch, we have shown that the same flexible particles we used to access caveolae can be easily loaded with a variety of drugs, bringing up the possibility of squeezing 300 nanometer bags of therapeutic cargo into 30nm caveolae.

  • Immunologist, E. John Wherry, Named Chair of Systems Pharmacology, effective July 1, 2018

    Monday, July 23, 2018

    E. John Wherry, PhD, has been appointed the new chair of the department of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania, effective July 1. Wherry is the Richard and Barbara Schiffrin President’s Distinguished Professor in the department of Microbiology and an international leader in the study of T cell exhaustion, which prevents optimal control of infections and can hamper anti-tumor immune responses.

  • Penn Medicine’s Garret FitzGerald, Cardiovascular Disease and Translational Medicine Expert, Elected to Italian Science Academy

    Monday, July 30, 2018

    Garret FitzGerald, MD, FRS, a professor of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania, and an international leader in cardiovascular disease research, has been elected as a foreign member of the Accademia Nazionale dei Lincei (Lincean Academy) – the Italian Academy of Science in Rome.

  • Therapy for Rare Cancers Receives FDA Approval Following Trials at Penn’s Abramson Cancer [Daniel A. Pryma, quoted]

    Tuesday, July 31, 2018

    The U.S. Food and Drug Administration (FDA) has approved the first ever non-surgical treatment for the rare neuroendocrine cancers pheochromocytoma and paraganglioma. The approval was based on a multi-center trial led by researchers in the Abramson Cancer Center of the University of Pennsylvania and was granted to Progenics Pharmaceuticals for AZEDRA (iobenguane I131). “This is a true breakthrough. Until today, there were no anti-tumor therapies available for patients with these tumors who were not candidates for surgery,” said the trial’s principal investigator Daniel A. Pryma, MD, an associate professor of Radiology and Radiation Oncology, chief of Nuclear Medicine and Clinical Molecular Imaging at Penn’s Perelman School of Medicine, and a member of Penn’s Abramson Cancer Center.

  • Dental plaque is no match for catalytic nanoparticles [featuring David Cormode]

    Tuesday, July 31, 2018

    Combine a diet high in sugar with poor oral hygiene habits and dental cavities, or caries, will likely result. The sugar triggers the formation of an acidic biofilm, known as plaque, on the teeth, eroding the surface. Early childhood caries is a severe form of tooth decay that affects one in every four children in the United States and hundreds of millions more globally. It’s a particularly severe problem in underprivileged populations. In a study published in Nature Communications this week, researchers led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Science used FDA-approved nanoparticles to effectively disrupt biofilms and prevent tooth decay in both an experimental human-plaque-like biofilm and in an animal model that mimics early-childhood caries.

  • Candidate for Universal Flu Vaccine Protects Against Multiple Strains in Preclinical Study [Drew Weissman quoted]

    Wednesday, August 22, 2018

    A modified-RNA vaccine elicits protective response in mice to a conserved region of the flu virus. “This vaccine was able to do something that most other candidate flu vaccines have not been able to do,” said study co-senior author Drew Weissman, MD, PhD, a professor of Infectious Diseases. “It was able to elicit protective responses against a conserved region that offers broad protection.”

  • Red-Blood-Cell “Hitchhikers” Offer New Way to Transport Drugs to Specific Targets [Ft. Vladimir Muzykantov and Jake Brenner]

    Tuesday, July 31, 2018

  • Letting nanoparticles hitchhike on red blood cells [Ft. Vladimir Muzykantov and Jake Brenner]

    Friday, July 20, 2018

  • Penn Medicines Garret FitzGerald MD FRS Elected to the German National Academy of Sciences

    Thursday, June 7, 2018

    Garret FitzGerald, MD, FRS, a professor of Systems Pharmacology and Translational Therapeutics at the Perelman School of Medicine at the University of Pennsylvania, and an international leader in cardiovascular disease research, has been elected to the Leopoldina, the German National Academy of Sciences, the oldest continuously existing academy of medicine and the natural sciences in the world. The award recognizes FitzGerald’s “scientific achievements and … personal standing.” He has been selected for membership in the Academy’s section on physiology and pharmacology/toxicology.

  • Penn-led Trial Shows AZEDRA Can Be Effective, Safe for Treatment of Rare Neuroendocrine Tumors [PI: Daniel A. Pryma]

    Tuesday, May 29, 2018

    A radiotherapy drug that treats the rare neuroendocrine cancers pheochromocytoma and paraganglioma can be both effective and safe for patients, according to the findings of a multi-center trial led by researchers in the Abramson Cancer Center of the University of Pennsylvania. The study showed AZEDRA led to a significant reduction in the cardiovascular side effects that are associated with these cancers while also stopping tumor growth. The study’s principal investigator Daniel A. Pryma, MD, Chief of Nuclear Medicine and Clinical Molecular Imaging at Penn’s Perelman School of Medicine, will present the results at the ASCO 2018 Annual Meeting in Chicago.

  • Penn Medicine Researcher, James Eberwine, Joins International Collaboration to Better Understand How Cells Regulate Energy Production

    Friday, May 4, 2018

    James Eberwine, PhD, the Elmer Holmes Bobst Professor of Systems Pharmacology and Translational Therapeutics in the Perelman School of Medicine at the University of Pennsylvania, is part of an international team of researchers, who will receive $1.25M over the next three years to better understand oxidative phosphorylation (OxPhos), a biological system that plays a key role in the production of energy, generation of free radicals, and cell death.

  • Calculus III for cells [Kathleen Stebe quoted]

    Monday, April 23, 2018

    Last year, researchers from the University of Pennsylvania revealed surprising insights into how cells respond to surface curvature. "We think of it as the cells doing calculus; the cells sense and respond to the underlying curvature,” says Kathleen Stebe of Penn’s School of Engineering and Applied Science. Now, the researchers, led by Stebe and recent engineering graduate Nathan Bade in collaboration with Randall Kamien of the School of Arts and Sciences and Richard Assoian of the Perelman School of Medicine, have published a follow up study that Stebe likens to “calc III” for cells, investigating how cells respond to more complex geometries. The research, which could enable new tools in biology and affect how physicians treat things like vascular disease, has been published in the Biophysical Journal.

  • Penn Cancer Researchers Receive $2.7 Million from V Foundation to Better Understand PARP Inhibitors and Treat BRCA Cancers [Roger A. Greenberg]

    Thursday, March 29, 2018

    Cancer researchers from the Perelman School of Medicine at the University of Pennsylvania and the Basser Center for BRCA in the Abramson Cancer Center of the University of Pennsylvania, have received two major grants from the V Foundation for Cancer Research. Funded projects will work to better understand and treat cancers in patients with inherited mutations of the BRCA1 and BRCA2 genes, which produce tumor-suppressor proteins. These mutations significantly increase the risk for breast and ovarian cancer as well as other types of cancer in women and men. The first grant, a three-year, $2.1 M Team Science Convergence Award, will be led by Roger A. Greenberg, MD, PHD, a professor of Cancer Biology, and Katherine L. Nathanson, MD, a professor of Medicine and Genetics.

  • A fake organ mimics what happens in the blink of an eye [Dan Huh]

    Tuesday, February 20, 2018

    For the first time, researchers used human cells to build a model of the surface of the eye that’s equipped with a fake eyelid that mimics blinking. This synthetic eye could be used to study and test treatments for eye diseases, researchers reported February 16 in a news conference at the annual meeting of the American Association for the Advancement of Science. This artificial eye is made of corneal cells (dark blue) surrounded by a ring of conjunctival cells (white), grown on a contact lens‒like surface. The device “blinks” when a hydrogel film slides over a channel containing artificial tears (black) and spreads the liquid over the cells. Dan Huh, a bioengineer at the University of Pennsylvania, and colleagues grew a ring of conjunctival cells — tissue that covers the white part of the eye — around a circle of corneal cells on a contact lens‒shaped platform. A faux eyelid made of a thin hydrogel film covers and uncovers the eye to spread tear fluid over the cells.

  • Jason Burdick Receives Heilmeier Research Award

    Jason Burdick, Professor in Bioengineering, has been named the recipient of the 2017-18 George H. Heilmeier Faculty Award for Excellence in Research for "pioneering contributions to designing and developing polymers for applications in stem cell biology and regenerative medicine." The Heilmeier Award honors a Penn Engineering faculty member whose work is scientifically meritorious and has high technological impact and visibility. It is named for George H. Heilmeier, a Penn Engineering alumnus and overseer whose technological contributions include the development of liquid crystal displays and whose honors include the National Medal of Science and Kyoto Prize. Burdick's research interests include developing degradable polymeric biomaterials that can be used for tissue engineering, drug delivery, and fundamental polymer studies.

  • Penn Researchers Develop an Injectable Gel that Helps Heart Muscle Regenerate after a Heart Attack [Jason Burdick]

    Wednesday, November 29, 2017

    In mammals, including humans, the cells that contract the heart muscle and enable it to beat do not regenerate after injury. After a heart attack, there is a dramatic loss of these heart muscle cells and those that survive cannot effectively replicate. With fewer of these contractile cells, known as cardiomyocytes, the heart pumps less blood with each beat, leading to the increased mortality associated with heart disease. Now, researchers at the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine have used mouse models to demonstrate a new approach to restart replication in existing cardiomyocytes: an injectable gel that slowly releases short gene sequences known as microRNAs into the heart muscle. The study was led by Edward Morrisey, Professor in Medicine, member of the Cell and Molecular Biology graduate group and Scientific Director of the Penn Institute for Regenerative Medicine in Penn Medicine; Jason Burdick, Professor in Bioengineering in Penn Engineering; Leo Wang, a graduate student in Burdick’s lab; and Ying Liu, a postdoctoral researcher in Morrisey’s lab. It was published in the journal Nature Biomedical Engineering.

  • First Microscopic Video of Blood Clot Contraction Reveals How Platelets Naturally Form Unobtrusive Clots [Team led by John W. Weisel]

    Wednesday, November 8, 2017

    The first view of the physical mechanism of how a blood clot contracts at the level of individual platelets is giving researchers from the Perelman School of Medicine at the University of Pennsylvania a new look at a natural process that is part of blood clotting. A team led by John W. Weisel, PhD, a professor of Cell and Developmental Biology, describes in Nature Communications how specialized proteins in platelets cause clots to shrink in size. To learn how a clot contracts, the Penn team imaged clots (networks of fibrin fibers and blood platelets) using an imaging technique called confocal light microscopy. The natural process of clot contraction is necessary for the body to effectively stem bleeding, reduce the size of otherwise obstructive clots, and promote wound healing. The physical mechanism of platelet-driven clot contraction they observed is already informing new ways to think about diagnosing and treating conditions such as ischemic stroke, deep vein thrombosis, and heart attacks. In all of these conditions, clots are located where they should not be and block blood flow to critical parts of the body. Evidence from a study published earlier this year from the Weisel lab suggests that platelets in people with these diseases are less effective at clot contraction, thereby contributing to clots being more obstructive. “Under normal circumstances, blood clot contraction plays an important role in preventing bleeding by making a better seal, since the cells become tightly packed as the spaces between them are eliminated,” Weisel said. “In this study, we unwrapped and quantified clot contraction in single platelets.” The team quantified the structural details of how contracting platelets cause clots to shrink, accompanied by dramatic structural alterations of the platelet-fibrin meshwork.

  • Penn Researchers Working to Mimic Giant Clams to Enhance the Production of Biofuel [Shu Yang]

    Thursday, November 2, 2017

    Alison Sweeney of the University of Pennsylvania has been studying giant clams since she was a postdoctoral fellow at the University of California, Santa Barbara. These large mollusks, which anchor themselves to coral reefs in the tropical waters of the Indian and Pacific oceans, can grow to up to three-feet long and weigh hundreds of pounds. But their size isn’t the only thing that makes them unique. Anyone who has ever gone snorkeling in Australia or the western tropical Pacific Ocean, Sweeney says, may have noticed that the surfaces of giant clams are iridescent, appearing to sparkle before the naked eye. The lustrous cells on the surface of the clam scatter bright sunlight, which typically runs the risk of causing fatal damage to the cell, but the clams efficiently convert the sunlight into fuel. Using what they learn from these giant clams, the researchers hope to improve the process of producing biofuel. Sweeney, an assistant professor of physics in the Penn School of Arts and Sciences, and her collaborator Shu Yang, a professor of materials science and engineering in the School of Engineering and Applied Science, refer to the clams as “solar transformers” because they are capable of absorbing bright sunlight at a very high rate and scattering it over a large surface area. When the light is distributed evenly among the thick layer of algae living inside the clam, the algae quickly converts the light into energy. After coming across Sweeney’s work, Yang struck up a collaboration to see if they could mimic the system by abstracting the principles of the clam’s process to create a material that works similarly. She and Ph.D. student Hye-Na Kim devised a method of synthesizing nanoparticles and adding them to an emulsion — a mixture of water, oil, and soapy molecules called surfactants — to form microbeads mimicking the iridocytes, the cells in giant clams responsible for solar transforming. Their paper has been published in Advanced Materials.

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Center for Targeted Therapeutics and Translational Nanomedicine

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