Technology  November 30, 2012

The researchers

UC Anschutz
Myron Levin
By Maggie Shafer

Dr. Myron Levin first began studying infectious disease to avoid going to war.

The University of Colorado professor of pediatrics and medicine graduated from Harvard Medical School in 1964, at the height of the Vietnam War. Levin knew that, like so many others, if he didn’t find his way into the public health service, he’d be drafted.

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Nothing like war to make cancer look appealing.

During his time at the National Cancer Institute, he had over 60 patients die battling leukemia. But it wasn’t the leukemia that killed them – it was other infectious viruses like chicken pox, taking advantage of a child’s weakened state.

“When I started at the cancer institute I thought I’d get into cancer, but instead I got into infectious disease,” he said. “And it’s a fascinating field to be in.”

Levin completed residency training in medicine at Albert Einstein College of Medicine in 1966, and infectious diseases fellowship training at Harvard Medical School in 1971. He worked for Harvard Medical School for more than 10 years, before coming to CU in 1982.

His work at the university’s School of Medicine on the Anschutz Medical Campus has led to the creation of Zostavax, a vaccine for shingles.

Shingles — a form of herpes — is caused by the same virus as chicken pox, which remains dormant in nerve cells even after the individual fully recovers. It can become active again as people age and their immune systems deteriorate. If left untreated, it can be deadly, especially for the elderly.

Zostavax, made by Merck & Co. Inc., is a live, weak version of the same virus. When injected, it causes the immune system to ramp up its defenses to the virus before the disease has a chance to take over.

“The reason people get shingles is that they lose their immunity to a virus that already lies in them,” Levin said. “As we get older, our immune system that keeps it from coming out starts to wane.”

Zostavax can reduce an adult’s risk of shingles by 50 percent, and in the cases it doesn’t prevent, it greatly attenuates.

While Levin started work on the drug in 1984, it was 2005 before it was finally licensed. Securing enough funding for research and testing took 15 years.

“Finding timely funding is a huge obstacle,” he said. “Many people have good ideas, and a lot just don’t make it.”

Today, about 20 percent of adults over 50 have received the vaccine. Levin attributes the lag time between the release and widespread use to the lack of marketing Merck originally did for it, due to a paucity of the vaccine. But now that supply is up, so is marketing.

“It’s really starting to catch on now,” he said.

Levin has continued to work on the vaccine, searching for a greater understanding of the virus, including how it maintains itself in the nerves and what causes it to come out of dormancy. He sees Zostavax, the first shingles vaccine attempt, as only the beginning of the process.

“The vaccine has given us principles that we can build on to build better vaccines,” he said.

Levin believes that both public and private investment in research is not only key to continued innovation, but an effective way to produce economic growth.

“Just as we put money into tourism, we should be putting money in to research,” he said.

“We have to make sure they (investors and legislators) understand the incredible capabilities of the med school campus.”

Colorado School of Mines
Terri Hogue
By MJ Clark

Water is a big issue throughout the West, but Colorado School of Mines professor Terri Hogue had to go east to find a school that took water as seriously as she does. She moved from California to Colorado in July.

“One of the things that attracted me to CSM was the focus and forward-thinking (approach) about water here,” she said. “They have a cross-department, cross-campus hydrologic sciences and engineering program. Water has become a big part of the mission here.”

The Colorado School of Mines, along with Stanford University, the University of California at Berkeley and New Mexico State University together established the Engineering Research Center for Re-inventing the Nation’s Urban Water Infrastructure. The four universities are sharing in a four-year, $18.5 million grant from the National Science Foundation to address the looming water crisis.

Hogue, an associate professor at CSM’s Civil and Environmental Department, is heading up the NSF’s Water Sustainability and Climate program to investigate urban ecosystems and water management that, ironically, will study water systems in her former hometown, Los Angeles.

Hogue and her fellow researchers will be asking some fundamental questions including, “What is the water being used for?” and “What services does that water use provide?”

For example, she said, “the cost of getting water to where it needs to be in L.A. is high — it’s one of the biggest energy consumers in the state. Is there any energy payback to the water use — like trees providing a cooling effect that lowers energy consumption?”

Closer to her new home, Hogue is also studying the impact of fire on hydrologic cycles, or the circulation and conservation of water.

“When fires happen, the soil surface is altered and water is prevented from getting into the soil,” she explained. “Ash clogs the pores and a waxy, hydrophobic layer forms. This takes awhile to break down and can reduce the amount of water reaching the groundwater system.”

The Waldo Canyon area in Colorado Springs — site of a devastating wildfire this summer — is her new laboratory, where multiple methods are being employed to treat the burned areas, depending on conditions such as burn severity, degree of slope, type of vegetation, and so forth.

As a result, “there are lots of little labs out there,” Hogue said. “We want to see if we can tweak out at all if the treatments (generally, different types of mulch) had any impact.”

In Southern California, she notes, “They typically don’t treat after fires. It’s expensive to lay down straw or wood mulch over large regions.”

The Waldo Canyon Fire is also interesting to her because of the high number of homes built close to wild areas and the potential for flooding and runoff.

In California’s Northern Sierra, Hogue also works on fuel treatments — thinning the forests to prevent catastrophic fires — and is studying whether fewer trees using water lead to extra water on the surface or in the ground.

As a newcomer to CSM, Hogue is still looking for graduate students to work on new research projects. Although she brought a few students with her from California, “I’m always looking for good students,” she said.

Recently, Hogue received news of her latest laurel: she was elected secretary for the hydrology section of the American Geophysical Union, the largest association of earth and space scientists in the world.

University of Colorado
Bruno Giacomazzo
By MJ Clark

If a picture is worth a thousand words, a video is worth many more and is perhaps the best way to explain the complex work being done by the University of Colorado’s Bruno Giacomazzo.

His most recent achievement is the subject of a video posted by NASA’s Goddard Space Flight Center in September after Giacomazzo led a team of astrophysicists that used computational models to explore the mergers of supersized black holes.

Set to appropriate space music, the supercomputer simulation illustrates what happens when black holes — each one millions of times more massive than our own sun — merge. The binary black holes orbit each other, rotating faster as they draw closer together.

Because these objects are so massive, they produce gravitational waves that undulate too slowly to be detected by ground-based facilities. At present, the only way to see what happens is to rely on the computer simulation.

According to NASA’s description, “Close to these titanic, rapidly moving masses, space and time become repeatedly flexed and warped. Just as a disturbance forms ripples on the surface of a pond, drives seismic waves through Earth, or puts the jiggle in a bowl of Jell-O, the cyclic flexing of space-time near binary black holes produces waves of distortion that race across the universe.”

Gravitational waves do not provide one crucial piece of information: the precise position of the source. To really understand the event, researchers need an accompanying electromagnetic signal — a flash of radiation (from radio waves to X-rays) that will allow them to pinpoint the merger’s host galaxy.

Understanding the electromagnetic counterparts of a merger requires tracking the interactions between the black holes, which can move at more than half the speed of light in the last few orbits, along with the hot plasma (magnetized gas) that surrounds them.

Giacomazzo and his team developed the super-computer simulations that for the first time show what happens in the plasma during the last stages of a black hole merger. The simulations were run on the Pleiades supercomputer at NASA’s Ames Research Center in California, with additional simulations run on the Ranger supercomputer at the University of Texas and the NASA Center for Climate Simulation at Goddard.

“What’s striking in the magnetic simulation is that the disk’s initial magnetic field is rapidly intensified by about 100 times, and the merged black hole is surrounded by a hotter, denser, thinner accretion disk than in the un-magnetized case,” Giacomazzo explained.

The most interesting outcome of the magnetic simulation is the development of a funnel-like structure — a cleared-out zone that extends up out of the accretion disk near the merged black hole.

“This is exactly the type of structure needed to drive the particle jets we see from the centers of black-hole-powered active galaxies,” Giacomazzo said.

Other projects Giacomazzo is working on include the development of the fully general relativistic magnetohydrodynamic code “Whiskey,” that is used to study several astrophysical phenomena including gamma-ray bursts, binary neutron stars, black hole binaries, and the accretion-induced collapse of neutron stars to form black holes.

University of Northern Colorado
Susan Keenan
By MJ Clark

University of Northern Colorado researcher Susan Keenan is out to swat mosquito-born viruses like malaria, dengue, yellow fever and West Nile virus – a family of viruses known as flaviviruses.

These viruses take a devastating toll on the Third World, as there are currently no clinically useful antiviral drugs available. And, as the rest of the world learned with the introduction of West Nile to the United States in 1999, disease doesn’t care where you live. West Nile is now endemic in 47 of the lower 48 United States.

Keenan’s area of expertise is what’s called “rational” drug design, and she’s working to find drugs that can prevent and/or treat these scourges. Since 2007, her partner in the lab has been Dr. Brian Geiss at Colorado State University.

Keenan and Geiss have developed a drug that binds to the protein critical for viral replication. By blocking the protein’s function, the virus can’t make the proteins it needs to replicate and the virus’ genome will lose protection and can be destroyed by the healthy cell it was trying to invade.

Keenan, who has a diverse educational background including a degree in chemistry, a Ph.D. in pharmacology and physiology, and postdoctoral work in computational chemistry, has trained in both computational aspects and in the lab using molecular biology tools. Although she’s worked in cancer and pain research, she says “work on relatively neglected diseases is really my passion.”

For the past decade Keenan has researched drug design for West Nile, malaria, yellow fever or dengue fever. Any of these flaviviruses can result in hospitalization or death.

The keystone of Keenan’s research is finding small molecules that inhibit the function of a protein or enzyme essential for the survival of the flavivirus.

First, the duo screened large chemical libraries for molecules that inhibited a specific enzyme, and then used computer modeling to find molecules that were best able to bind to the viral protein. One of the molecules they discovered reduced virus replication in cells by a factor of 1,000.

Now that the researchers have confirmed that the drug works against several different viruses, they are working to improve the drug’s effectiveness and testing how well the drug works in animal models. There is a lot more work to be done before their drug is ready to be used as an investigational new drug on humans.

“I would love for us to be at the point where we have an investigational new drug in the early phases of clinical trials for the treatment of diseases caused by flaviviruses,” Keenan said. ” We have a long way to go, but I am excited that we are making inroads toward that goal.”

University of Wyoming
Keith Carron
By MJ Clark

In the original “Star Trek” series, one of the most interesting devices was the tricorder: a little box that Spock would wave in the general direction of an object and which then would report on the exact chemical composition of that object. It was very handy when dealing with hostile alien environments.

Today, military personnel facing rooms that may be booby-trapped with explosives are able to do much the same with devices that are manufactured in Laramie, Wyo.

The devices are called Raman spectrometers, which illuminate material with lasers and then identify the material and its potential hazards from a safe distance.

These spectrometers are manufactured by DeltaNu, a company founded in 1998 by a pair of University of Wyoming professors: serial inventor Keith Carron and Robert Corcoran, along with Gene Watson, a longtime tech entrepreneur.

DeltaNu was sold to Silicon Valley tech firm Intevac Inc. in 2007 with the stipulation that the company remain in Laramie.

Carron, who left academics to head DeltaNu and first served as its general manager, then vice president at Intevac, realized after two years that, “I still like research, and I didn’t really like doing spreadsheets and managing a business like that.”

UW asked him to come back to academia and head the chemistry department. “So, in a way, I’m back into management,” he said, “but I’m also back into research, so I’m very happy.”

Carron’s current research is along the same lines as the technology that developed into DeltaNu. “This is what entrepreneurs do,” he said. “We’re always innovating, thinking about how to make money.”

Carron and his two graduate students have just published three papers that have been well-received. The trio has developed a new class of materials for surface-enhanced Raman spectroscopy consisting of hollow, buoyant silica microspheres coated with gold nanoparticles. The new materials allow for a novel type of molecular assay dubbed “lab-on-a-bubble” or LoB.

Carron explained that the LoB are “little microscopic bubbles that pull the assay to the top of the solution. When the assay results are pulled to one spot, it makes the test more sensitive.”

For example, the team has tested detection of cyanide — a useful model for environmental studies — and found that they obtained a surface-enhanced Raman scattering signal 28 times larger using the LoB system than with the more conventional approach of using colloidal gold nanoparticles that didn’t float.

Not even on “StarTrek” did they imagine tricorders in the guise of tiny, gold-dusted micro-bubbles.

Colorado State University
Karolin Luger
By MJ Clark

Unraveling the mysteries contained in the proteins that organize and bind DNA into packages small enough to fit comfortably into cell nuclei has won Colorado State University’s Karolin Luger multiple awards and honors — and may even hold the secret to a cure for some cancers.

Since joining the faculty of CSU in 1999, Luger has become a University Distinguished Professor in Biochemistry, earned a Searles Scholarship and is the university’s only Howard Hughes Medical Investigator (an honor she has won twice, and which funds half of her research lab, as well as 100 percent of her salary).

A description of her work doesn’t exactly roll off the tongue.

“We’re looking at how the proteins involved in genome packaging contribute to the genome,” she explained. “There is additional information that’s embedded in addition to the DNA sequence.”

That additional information is referred to as epigenetic, literally “above genetics.” It is this epigenetic information that accounts for the differences found in identical twins. And, the differences get more pronounced as twins age and experience different environments.

“The saying, ‘DNA is not your destiny’ is really true,” Luger said. “Your DNA is smarter than just your DNA sequence.”

Bundling DNA is not an easy task. Mammalian DNA is about 2 meters long, while the place it occupies within the cell is 10 one-millionths of a meter wide. The DNA needs to be unbundled for use, and rebundled again.

One area that Luger is interested in is how packaged DNA structures react to DNA damage and how they repair it. For example, cells have trouble repairing DNA due to damage inflicted by too much sunshine. Information on how DNA is repaired can have a big impact on cancer research.

Luger’s biophysics lab “has a lot of fancy, complicated equipment” she says, admitting to being “a bit of a gear head.” However, she also sees herself as a small business owner.

“Everyone’s raving about the importance of small business for the economy, while at the same time giving higher education a bad rap,” Luger said. “I would maintain that they’re not that separate.… My lab employs 20 people. I get grants from foundations and trust funds, and we buy things in the local economy.

“Our product is not something that you can touch, but it is knowledge and it is training. … Undergraduates who would otherwise fry hamburgers or mow lawns get a full-time summer job in my lab, and this includes thorough training in a working laboratory. This experience often leads them to pursuing a career in research.”

UC Anschutz
Myron Levin
By Maggie Shafer

Dr. Myron Levin first began studying infectious disease to avoid going to war.

The University of Colorado professor of pediatrics and medicine graduated from Harvard Medical School in 1964, at the height of the Vietnam War. Levin knew that, like so many others, if he didn’t find his way into the public health service, he’d be drafted.

Nothing like war to make cancer look appealing.

During his time at the National Cancer Institute, he had over 60 patients die battling leukemia. But it wasn’t the leukemia that killed them – it was other infectious viruses like chicken…

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