RNA is the bridge between the DNA molecule and the proteins that carry out the functions of life, but probing the intricacies of the RNA molecule deep within the cells it influences is a major challenge. Studying gene expression in cells in culture outside of their natural environment doesn’t always provide a true picture. As James Eberwine, professor of pharmacology at the University of Pennsylvania’s Perelman School of Medicine, notes, “the tissue microenvironment shapes the RNA landscape of individual cells.” That means that important insight about cell function, disease processes, or drug behavior might be missed by observations done outside that highly specialized microenvironment.

But Eberwine and his colleagues — including chemists and biologists in Penn’s School of Arts & Sciences —  have devised a revolutionary technique for targeting and observing the RNA of a single cell without disrupting its surroundings. Called TIVA (Transcriptome In Vivo Analysis), the method uses a customized “Swiss Army Knife” molecule to tag the RNA inside cells. The TIVA tags remain inert until they’re activated by a laser with a specific wavelength; this breaks open the molecule, revealing preciously hidden parts that can bind to RNA. The precision of the activating laser means that the tags can be introduced to a large tissue culture, but deployed only within a single cell of interest, allowing the RNA within just that cell to be isolated, studied and measured as desired.

Eberwine and his team have so far used the TIVA technique to examine gene expression in single neurons within intact brain tissue, providing a previously unavailable functional window into the cellular universe.

As one of the directors of the Penn Genome Frontiers Institute, Eberwine is also at the forefront of other interdisciplinary research initiatives that seek to understand the role of RNA’s various forms in health and disease.

If we can land on the moon, why can’t we cure cancer?  For decades, the only answer to that clichéd question has been that cancer is a far more complex and elusive problem than going to the moon.  And, like the moon missions, the approaches to cancer have tended to be big, ambitious, and aggressive, concentrating on attacking the disease directly through surgery, radiation, and drugs.

But Carl June and his colleagues at the University of Pennsylvania’s Perelman School of Medicine have taken a different approach to the question.  Rather than targeting cancer from outside, he has found a way to subvert it from within, by reprogramming the body’s own natural defenses to treat cancer cells as the deadly enemy they are. Through the genetic modification of T cells, a normal part of the human immune system, they have developed a devastating new weapon against cancer that has completely eradicated the disease in a number of patients.  Already hailed as perhaps the biggest cancer breakthrough in years, it may point the way to treating many forms of cancers.

The June team’s technique also drafts an unexpected ally into the cancer fight: a disabled form of HIV.  With a harmless, defanged variety of the pathogen, June uses its ability to inject genetic material into other cells to modify a patient’s T cells and turn them into “hunter cells” that will seek out and destroy cancer.

            After already achieving startling success in a number of patients with intractable leukemias and hopeless prognoses, June and his research team are working to expand the T cell strategy against other forms of cancer and perhaps even other incurable diseases.  Working in a collaboration with Novartis, June and the University of Pennsylvania intend to bring the concepts of cellular immunotherapy to full flower, saving lives that would have been lost only a few years before.

When a heart attack strikes, seconds count. Having a cardiac defibrillator device within immediate reach and ready to use can be the difference between life and death.  The dilemma is that despite the fact that automated external defibrillator (AED) devices are widespread throughout America’s public spaces, many people remain unaware of their presence — costing precious seconds in an emergency.

Raina Merchant, an assistant professor of emergency medicine at the University of Pennsylvania’s Perelman School of Medicine, is working to change that.  In 2012, she led the MyHeartMap Challenge in Philadelphia, which used crowdsourcing techniques to find and identify AEDs throughout the city. More than 300 teams of volunteers ranged throughout Philadelphia, using a specially-designed smartphone app to pinpoint about 1,500 AEDs in 500 buildings and to record geocoding data such as precise GPS coordinates. The data was used to create a city-wide map for use by 911 dispatchers and other emergency personnel.

Now Merchant is building upon that effort with the Penn Defibrillator Design Challenge, which will enlist volunteer artists and designers nationwide to come up with eye-catching and creative artwork to attract attention to AEDs in public spaces. “By incorporating artwork into important public health messages, we’ll make an indelible impression upon the viewer, so they’ll be able to identify AEDs and feel empowered to use them in an emergency,” says Merchant. Kicking off the campaign is a striking project in Philadelphia’s historic 30th Street Station, done in collaboration with Penn’s School of Design.

            In 2013, Merchant was named director of the Social Media Lab at the Penn Medicine Center for Health Care Innovation. In that position, her aim is to use the new 21st Century tools of social media in all its forms — the internet, crowd sourcing, smart phone technology — to increase awareness and involvement in critical public health issues, both to promote education and ultimately, to save lives.

One of the most promising scientific innovations of the past several decades is the carbon nanotube, an incredibly tiny structure with properties and applications that are just beginning to be realized. A.T. Charlie Johnson, a Professor of physics in the University of Pennsylvania’s School of Arts & Sciences, is one of the pioneers. As director of Penn’s Nano/Bio Interface Center, his work is crossing traditional boundaries between physics and biology to invent new uses for these structures and for graphene, the single-atom-thick sheet of carbon that is essentially an unrolled carbon nanotube.

The great strength and sensitive electrical characteristics of carbon atoms in nanotubes and graphene give them uniquely versatile potential. “The big picture is integrating nanotechnology with biology,” Johnson says. He’s doing that in various ways, among them creating a working interface between the olfactory receptor proteins that give us our sense of smell and a transistor composed of carbon nanotubes, resulting in a device that can detect the chemical signals of drugs and even disease with extreme sensitivity. Other carbon nanotube-based devices designed by Johnson and his research team use antibodies made in response to a Lyme disease protein, providing a precise diagnostic tool that can potentially the disease much earlier than existing techniques.

Johnson has also developed a more efficient and economical method of making graphene sheets, bringing their commercial potential closer to practical realization. His UPstart company, Graphene Frontiers, is working steadily toward the goal of manufacturing graphene in large quantities for industrial applications.

Anyone who’s taken any sort of medication knows how expensive it can be. Specialized drugs for serious diseases, particularly vaccines, can cost thousands of dollars to transport and distribute, placing them out of reach for many of the people who desperately need them. To molecular biologist Henry Daniell, a professor in the University of Pennsylvania School of Dental Medicine, that hard economic reality seemed fundamentally wrong. “If you have something that saves lives, you have an obligation to make it available to everyone,” he says.

Daniell set out to change things by finding a new way to deliver immunizing proteins. One reason that many drugs and vaccines are so expensive is that, because they contain killed or deactivated organisms, they need to be kept refrigerated to ensure their safety and effectiveness. That makes it a challenge to get them to remote areas where they’re most needed.

Daniell has found a cheaper and more efficient way: using plants. With their genetic malleability, cellular toughness, and ease of cultivation, plants are an ideal drug delivery system, and Daniell is using all of these qualities to demonstrate the practicality of this approach. In 2012, Daniell showed that lettuce engineered to express an insulin-promoting protein could all but cure Type 1 diabetes in mice.  A 2010 study used a plant-based vaccine to control immune reactions and stave off death in hemophilic mice. Thanks to a Gates Foundation grant, Daniell’s lab is also working on a broad-based polio vaccine, with the aim of eliminating the disease permanently.

Daniell’s work spans a broad range of disciplines, and accordingly, he is collaborating across several Penn schools and departments. Within the Perelman School of Medicine, he is looking to join forces with graduate immunology and gene therapy programs.

Nanotechnology is all about influencing the macro world in which we live by understanding and controlling the subatomic world invisible to our eyes. Shu Yang, associate professor in the School of Engineering and Applied Science, has addressed a macroscale problem at the nanoscale by developing a nanoparticle coating that’s both transparent and superhydrophobic (impervious to water). The invention is also the mainstay of the new UPstart company Nelum Sciences.

The water-based coating is composed of nanoscopic particles that can be sprayed on any surface, whether microelectronic circuitry, solar panels, clothing, or something as simple as window glass. The coating changes the surface’s characteristics so that liquids bead into spheres and roll off instead of sticking. As a bonus, the liquid carries off any dust or dirt particles it contacts along the way. With Nelum’s superhydrophobic coating, nothing more than a rainstorm is needed to clean skyscraper windows or vast arrays of solar panels.

Yang is also part of an interdisciplinary team, including Randall Kamien of the Department of Physics and Astronomy in Penn’s School of Arts & Sciences and Kathleen Stebe, deputy dean for research in Engineering, that has also already developed ways of manipulating and rearranging liquid crystals at the nanoscale by creating and controlling patterns through mechanical techniques and templates. These techniques can lead not only to new types of liquid crystal displays and devices, but may be the key to building and manufacturing nanoscale devices and materials through a “directed assembly” approach.

For those with bone fractures or diseases, any method to improve or accelerate normal bone growth is welcome, because the normal process can seem slow and arduous. Kurt Hankenson, associate professor in the Penn School of Veterinary Medicine, has hit upon a new protein pathway to stimulate bone cell growth in stem cells that may lead both to faster healing from fractures and to treatments for a rare condition called Alagille syndrome.

Although it was already known that a protein known as BMP was a major player in stimulating stem cells to become bone cells, it’s proven of somewhat limited effectiveness in clinical treatments, so the quest has continued for new and better ways of stimulating bone growth. Hankenson and his collaborators at Penn Vet focused on Jagged-1, a protein in the Notch signaling pathway, after previously identifying its role in bone formation.  When they tried introducing Jagged-1 to human stem cells, they found that the protein kicked the transformation of stem cells to bone-forming osteoblasts into high gear.

Jagged-1 mutations are also implicated in Alagille syndrome, a metabolic disorder that causes skeletal weakness and easily broken bones. Hankenson is now working with researchers at Perelman School of Medicine and Children’s Hospital of Philadelphia to further investigate this connection and the possibility that genetic manipulation of Jagged-1 could lead to clinical therapies.

To develop Jagged-1’s bone-forming potential into practical technologies for fracture repair, spinal fusion, bone reconstruction, and other treatments, Hankenson joined with his former doctoral student Michael Dishowitz to form the UPstart company Skelegen. Their goal is the perfection of new ways to deliver Jagged-1 precisely and efficiently to wherever it’s needed in the body to repair, restore, and strengthen bone tissue, whether damaged through injury or disease.

One of the greatest stressors on America’s health care system is the sheer number of patients it handles — and the enormous amount of data they generate.  But because it is needed for making decisions on patient care and treatment, handling, using, and interpreting that data properly is an indispensable part of a caregiver’s decision-making process. How to ensure that a patient gets the care she needs when she needs it?  How long should a patient stay in one expensive health care facility before he can be transferred to a more economical one? What if a patient is discharged from the hospital too soon, without adequate follow-up care, only to end up back in the hospital in worse condition?

Faced with such questions, Kathryn Bowles, a professor in the University of Pennsylvania School of Nursing, conceived a unique solution.  Developed by Bowles, Penn engineering and Wharton School graduate Eric Heil, and their colleagues over a decade of research, their Discharge Decision Support System (D2S2) is a sophisticated software package that pulls together, evaluates, and rates key data about a patient upon admission to the hospital. It then helps to identify high-risk patients, suggest personalized care plans, make referrals, and create post-acute-care treatment strategies that greatly reduce the readmission of patients to the hospital because of inadequate follow-up care. Studies conducted at the University of Pennsylvania Health System hospitals and Thomas Jefferson University Hospitals have demonstrated that the use of D2S2 has resulted in a dramatic reduction of readmissions.

In 2010, Bowles and Heil founded the UPstart company RightCare Solutions to further develop and market the D2S2 software. Through a synthesis of computer science, data informatics, and years of clinical nursing experience, the company aims to improve the medical care and thus the lives of patients and their families.