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BOOTH

Ray Booth creates a new drug for schizophrenia

Raymond G. Booth, professor of pharmaceutical sciences and chemistry

Booth has been on a 25-year mission to develop a drug that does a better job treating schizophrenia and other psychiatric disorders, including addiction. And now he’s close to seeing his vision become reality.

Medications to manage schizophrenia have existed since the 1950s. But their side effects—sedation, neurological disorders, and extreme weight gain—mean patients often don’t stick to treatment plans. And current drugs aren’t nuanced enough to correct the imbalanced brain neurotransmission that underlies psychiatric disorders.

But Booth’s drug, Bromopatin, acts in a novel way to rebalance neurotransmission of the brain neurochemical serotonin. Bromopatin turns down activity of some serotonin receptors while turning up activity for others. Preclinical testing suggests no serious side effects.

Booth is working with pharmaceutical development partners toward clinical trials. If all goes well, Bromopatin could be available in a few years, bringing hope to the millions of people coping with schizophrenia and other psychiatric disorders.

CARRIER_FINAL

Rebecca Carrier advances drug delivery

Rebecca Carrier, Associate Professor of Chemical Engineering

Scientists and doctors have long known that food digestion affects the way the body absorbs not just nutrients, but also drugs. Fat molecules, in particular, can help people absorb drugs, including oral chemotherapy treatments, more efficiently.

What we have yet to discover are the details of this process that would enable doctors to fine-tune drug dosages, minimize side effects, and make drug delivery more efficient. But Carrier may soon be able to start filling in those knowledge gaps.

With funding support from the National Institutes of Health, she and her team are gaining a clearer understanding of the mechanisms behind this phenomenon.

In one project, they’re developing predictive models for how ingested lipids, or fat molecules, change the way the body absorbs different compounds. In a second project that will help advance the modeling goal, Carrier’s lab is exploring the properties of the gastrointestinal mucus barrier, which simultaneously protects the body from harmful bacteria while allowing the absorption of needed vitamins and nutrients.

LIVEMORE

Carol Livermore integrates origami into tissue engineering

Carol Livermore, Associate Professor of Mechanical and Industrial Engineering

Engineering tissue to create livers and other human organs for transplant is a fast-growing field in biotechnology. To overcome one of its critical challenges, Livermore is applying the ancient Japanese art of paper folding, origami.

Current tissue engineering methods lack precision in placing blood vessels and other organic structures. Backed by a $2 million grant from the National Science Foundation, Livermore and her team are attempting to solve that by working with origami artists and theorists to assemble different cell types onto a biocompatible, two-dimensional scaffold—the “paper.” The example Livermore holds here was created by renowned origami artist Robert Lang.

By folding the scaffold correctly, they could construct a three-dimensional block of tissue with the blood vessels and other structures running through it, she says—much like some origami designs neatly fold into a 3D object, such as a bird or flower.

They have successfully tested an initial stage of this technique, inducing mouse cells to self assemble at specific locations on two-dimensional surfaces. The next step, says Livermore, will be determining how to “unfold” an existing piece of tissue to provide a template for the scaffold.

Alessandro Vespignani

Alessandro Vespignani maps out pandemics

Alessandro Vespignani, Sternberg Family Distinguished University Professor of Physics, Computer Science, and Health Sciences

Alessandro Vespignani, Sternberg Distinguished Professor of Physics, Computer Science, and Health Sciences

Vespignani is a pioneer in the emerging field of digital epidemiology, which promises to revolutionize the way we approach public health issues involving the spread of infectious diseases.

He notes that it took nearly a decade for the Black Plague to spread through Europe, while, thanks to modern transportation, the 2009 H1N1 pandemic swept across the globe in just four months.

Vespignani has developed computational modeling tools that would transform preemptive public-health efforts the next time a contagion decides to hitch a lightning–fast ride around the world.

Using data such as airline traffic and cell phone usage, Vespignani creates maps of human mobility across the planet. Combining that data and the specific dynamics of a disease, his computational models can predict epidemic outbreaks with great precision. In fact, Vespignani and his team confirmed that their model accurately predicted—with a lead time of several months—the peak of the 2009 H1N1 outbreak in 42 countries in the Northern Hemisphere.

Michael Pollastri

Michael Pollastri takes on neglected diseases

Michael Pollastri, associate professor of chemistry and chemical biology

Pollastri’s novel approach to curing African sleeping sickness—the deadly, parasitic disease that affects the world’s poorest populations—has the potential to reframe the global effort to wipe out tropical diseases.

Using results from drug discovery efforts for other diseases, Pollastri’s team sifts through thousands of drugs—both under investigation and FDA-approved—searching for those that can be repurposed to stop the parasite.

His team hunts for medicines that inhibit drug targets in human cells—such as those important to cancer growth—that are also present in trypanosoma brucei, the culprit bacteria.

The compounds are tested in culture. When the team finds a hit—and they’ve identified several already—they make chemical alterations to tune the drug to work against parasites.

Pollastri’s method—sometimes known as “target class repurposing”—could deliver new drugs more quickly and at lower cost, critical considerations when a researcher is targeting diseases that hit the poor the hardest.

LEWIS-K

Kim Lewis identifies a sleeping cause of infection

Kim Lewis, University Distinguished Professor of Biology

Lewis’s original work on persister cells could refocus the direction of antibiotic drug development by demonstrating that bacterial resistance to antibiotics is not the only cause of chronic infections.

He has discovered that persister cells, which survive antibiotic treatment by going dormant, are largely responsible for recalcitrance of those infections. Once an antibiotic leaves a person’s system, those sleeper cells reawaken and begin their work anew.

Lewis and his team have posited that if they could kill these expert survivors, they could cure chronic infections—even those resistant to multiple antibiotics such as methicillin resistant staphylococcus aureus or MRSA.

In a ground­breaking study published in the journal Nature, they reported that a drug called ADEP “wakes up” the dormant cells and then initiates a self-destruct mechanism. The approach completely eradicated MRSA cells in an infected mouse.

The team is pursuing compounds similar to ADEP for their potential to treat other infections, as well as disease types involving rogue cells, including cancer.

BARABASI

Albert-László Barabási maps the disease network

Albert-László Barabási, Distinguished Professor of Physics

One of the world’s foremost network scientists, Barabási is leading an interdisciplinary team of researchers on a quest to construct the human “diseasome”—the sum of all human diseases and the ways they relate to one another.

This map of human diseases would revolutionize medicine on all levels, says Barabási, enabling researchers to understand the molecular and genetic linkages between one disease, like asthma, and other respiratory diseases.

The team has already developed a map of 70 of the most common diseases based on their protein and metabolite interactions. As the pool of knowledge about those molecular interactions expands, so will the map.

Once the diseasome is fully mapped, Barabási says, physicians could use individual genetic mutations as a predictor of future health. And pharmaceutical researchers would have a powerful tool to design drugs with greater precision and effectiveness.

CLARK

Heather Clark unlocks the brain’s chemistry

Heather Clark, associate professor of pharmaceutical sciences

Clark is a leading researcher in the field of nanosensors, and she is applying her expertise to reveal what has eluded generations of scientists: how, exactly, do the chemicals in our brains interact to generate emotions, thoughts, memories, and actions?

More precisely, how do neurotransmitters like glutamate, dopamine, or serotonin behave differently in a patient with Alzheimer’s or schizophrenia versus someone with a healthy brain? Without that knowledge, neuroscience researchers and clinicians are practically working in the dark.

To unlock the brain’s chemical secrets, Clark and her team are in the early stages of developing nanoparticles containing a particular menu of molecules.

These nanosensors will react with different chemicals, producing a detectable signal of brain chemistry in real time and allowing her team to map the brain in greater detail than ever before. This more nuanced understanding of how the brain works will enable an entirely new, and targeted, line of therapies to treat neurological conditions.

Carol Livermore integrates origami into tissue engineering

Carol Livermore, Associate Professor of Mechanical and Industrial Engineering

Engineering tissue to create livers and other human organs for transplant is a fast-growing field in biotechnology. To overcome one of its critical challenges, Livermore is applying the ancient Japanese art of paper folding, origami.

Current tissue engineering methods lack precision in placing blood vessels and other organic structures. Backed by a $2 million grant from the National Science Foundation, Livermore and her team are attempting to solve that by working with origami artists and theorists to assemble different cell types onto a biocompatible, two-dimensional scaffold—the “paper.” The example Livermore holds here was created by renowned origami artist Robert Lang.

By folding the scaffold correctly, they could construct a three-dimensional block of tissue with the blood vessels and other structures running through it, she says—much like some origami designs neatly fold into a 3D object, such as a bird or flower.

They have successfully tested an initial stage of this technique, inducing mouse cells to self assemble at specific locations on two-dimensional surfaces. The next step, says Livermore, will be determining how to “unfold” an existing piece of tissue to provide a template for the scaffold.