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February 2007
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April 2007

Ultrathin films deliver DNA as possible gene therapy tool

Gene therapy — the idea of using genetic instructions rather than drugs to treat disease — has tickled scientists’ imaginations for decades, but is not yet a viable therapeutic method. One sizeable hurdle is getting the right genes into the right place at the right time.

Chemical and Biological Engineering Assistant Professor David Lynn and his colleagues have created ultrathin, nanoscale films composed of DNA and water-soluble polymers that allow controlled release of DNA from surfaces. When used to coat implantable medical devices, the films offer a novel way to route useful genes to exactly where they could do the most good.

Lynn has used his nanoscale films to coat intravascular stents, small metal-mesh cylinders inserted during medical procedures to open blocked arteries. While similar in concept to currently available drug-coated stents, Lynn's devices could offer additional advantages. For example, Lynn hopes to deliver genes that could prevent the growth of smooth muscle tissue into the stents, a process which can re-clog arteries, or that could treat the underlying causes of cardiovascular disease.

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National Cancer Institute Renews $1.4 Million Grant For MRI Brain Tumor Research at Medical College

            The National Cancer Institute has awarded a five-year $1.4 million renewal grant to the Medical College of Wisconsin. It will fund continued development of magnetic resonance imaging (MRI) contrast agent methods to study angiogenesis the rapid new growth of blood vessels-- in brain tumors.

Kathleen Schmainda, Ph.D., associate professor of radiology is the ongoing principal investigator. This is the second successful renewal of the grant that was first awarded in 2003.

“Patients with brain tumors are in desperate need of new therapies,” says Dr. Schmainda. “Recent clinical studies combining anti-angiogenic agents with conventional therapies have shown significant improvements in patient response, leading to the first FDA-approved anti-angiogenic agents. Yet, to fully realize the promise of combined therapies, we need non-invasive methods that can answer critical questions about how these agents work and how to combine them optimally.”

Study findings could improve the application and interpretation of MRI dynamic contrast methods to evaluate tumor angiogenesis and combined therapeutic strategies for the benefit of brain tumor patients.

Dr. Schmainda, who holds a secondary appointment in biophysics, is a faculty member of the Medical College’s Functional Imaging Research and Biotechnology and Bioengineering Centers.

She received her BSE in biomedical engineering from Marquette University in 1986, MA and MS degrees in electrical engineering from Massachusetts Institute of Technology in1989, and Ph.D. degree in medical engineering from Harvard-MIT, in 1993. She also completed a postdoctoral fellowship in MRI at Massachusetts General Hospital in Charlestown, Mass. in 1995.

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Stem cell therapy shows promise for rescuing deteriorating vision

MADISON - For the millions of Americans whose vision is slowly ebbing due to degenerative diseases of the eye, the lowly neural progenitor cell may be riding to the rescue.

In a study in rats, neural progenitor cells derived from human fetal stem cells have been shown to protect the vision of animals with degenerative eye disease similar to the kinds of diseases that afflict humans. The new study appears today (March 28) in the journal Public Library of Science (PLoS) One.

The lead author of the study, University of Wisconsin-Madison researcher David Gamm, says the cells - formative brain cells that arise in early development - show "some of the best rescue, functionally and anatomically" of any such work to date. In animals whose vision would typically be lost to degenerative retinal disease, the cells were shown to protect vision and the cells in the eye that underpin sight.

The new findings are important because they suggest there may be novel ways to preserve vision in the context of degenerative diseases for which there are now no effective treatments. Macular degeneration, an age-related affliction that gradually destroys central vision, is a scourge of old age, robbing people of the ability to read, recognize faces and live independently.

The finding that the brain cells protected the cells in the eye was a surprise, according to Raymond D. Lund, an author of the new study and an eye disease expert at the University of Utah and the Oregon Health and Sciences University. The neural progenitor cells, which arise from stem cells and further differentiate into different types of cells found in the central nervous system, were being tested for their ability to deliver another agent, a growth factor that has been shown to be effective in treating some types of degenerative disease.

What was surprising, say Gamm and Lund, was that the cells alone demonstrated a remarkable ability to rescue vision.

"On their own, they were able to support retinal cells and keep them alive," says Lund, who has conducted pioneering studies of cell therapy for eye disease. "We didn't expect that at all. We've used a number of different cell types from different sources and these have given us the best results we've ever got."

How the cells act to preserve the deteriorating eye cells remains unknown, says Gamm. Like all cells, neural progenitor cells do many things and secrete many different types of chemicals that may influence the cells around them.

"The idea was to test the cells as a continuous delivery system" to shuttle an agent known as glial cell line-derived neurotrophic factor or GDNF, Lund explains. "It's not a sensible thing to inject the eyes many times over years. The idea was to use the cells as a continuous delivery system, but we found they work quite well on their own."

Lund has experimented with other cell types as therapies for preserving vision. The neural progenitor cells, a cell model developed by Wisconsin stem cell researcher Clive Svendsen, have been used experimentally to deliver the same growth factor in models of Parkinson's disease and Lou Gehrig's disease. Svendsen is also an author of the new PloS One report.

"It seems that the cells in and of themselves are quite neuroprotective," says Gamm. "They don't become retinal cells. They maintain their own identity, but they migrate within the outer and inner retina" where they seem to confer some protection to the light-sensing cells that typically die in the course of degenerative eye disease.

For researchers, the work is intriguing because the progenitor cells come from the brain itself, and not from the part of the nervous system devoted to vision.

"This cell type isn't derived from the retina. It is derived from the brain," says Gamm. "But we're not asking it to become a retina. They survive in the environment of the eye and don't disrupt the local architecture. They seem to live in a symbiotic relation ship" with retinal cells.

Gamm and Lund emphasize that the new work is preliminary, and that much remains to be done before the cells can be tested in humans: "The first thing is to show that something works, which we have done," says Lund. "Now we need to find out why, but this is a good jumping off point. "

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From a failure comes success

HARVEY BLACK For the State Journal

Gillware is a Madison company whose beginning was failure - specifically the failure of the hard drive on the computer of Tyler Gill, one of its founders.

The year was 2003.

The UW-Madison student was faced with what could be called the nightmare of anyone who uses a desktop or laptop computer.

Could he find a company to recover the data on that failed hard drive?

"I was looking around and couldn't find anything cheaper than $1,200 or $2,500. I didn't have $200 to spend on it," he said.

The hard drive is a thin, rapidly spinning disc on which all the computer's data and operating software are stored.

If it fails - and it can fail for mechanical, electronic or software reasons - a computer owner is faced with a serious problem.

Can the data, which can include everything from personally valuable photos to business information, be recovered?

Well, Tyler Gill and his roommates - including his brother, Brian, and Greg Piefer - started a company called Gillware with that mission in mind. Today, Tyler Gill is vice president and chief operating officer of the company.

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New developments in 'artificial photosynthesis'

Inspired by nature, scientists explore pathways to clean, renewable solar fuel

CHICAGO, IL -- Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory are trying to design catalysts inspired by photosynthesis, the natural process by which green plants convert sunlight, water, and carbon dioxide into oxygen and carbohydrates. The goal is to design a bio-inspired system that can produce fuels like methanol, methane, and hydrogen directly from water and carbon dioxide using renewable solar energy. Four Brookhaven chemists will discuss their research on this so-called "artificial photosynthesis" at the 233rd National Meeting of the American Chemical Society.

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With cellulosic ethanol, there is no food vs. fuel debate according to MSU scientist

CHICAGO — As more and more corn grain is diverted to make ethanol, there have been public concerns about food shortages. However, ethanol made from cellulosic materials instead of corn grain, renders the food vs. fuel debate moot, according to research by a Michigan State University ethanol expert.

Bruce Dale, an MSU chemical engineering and materials science professor, has used life cycle analysis tools, which include agricultural data and computer modeling, to study the sustainability of producing biofuels – fuels such as ethanol and biodiesel that are made from renewable resources.

Dale will present his findings today at the American Chemical Society annual meeting in Chicago.

"We grow animal feed, not human food in the United States," Dale said. "We could feed the country's population with 25 million acres of cropland, and we currently have 500 million acres. Most of our agricultural land is being used to grow animal feed. It's a lot simpler to integrate animal feed production into cellulosic ethanol production than it is to integrate human food production. With cellulosic ethanol, the 'food vs. fuel' debate goes away."

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Stem cells speed growth of healthy liver tissue

OAK BROOK, Ill.—For the first time, researchers have used adult bone marrow stem cells to regenerate healthy human liver tissue, according to a study published in the April issue of the journal Radiology.

When large, fast-growing cancers invade the liver, some patients are unable to undergo surgery, because removing the cancerous tissue would leave too little liver to support the body.

Researchers at Heinrich-Heine-University in Düsseldorf, Germany, used adult bone marrow stem cells to help quickly regenerate healthy liver tissue, enabling patients to eventually undergo a surgical resection.

“Our study suggests that liver stem cells harvested from the patient’s own bone marrow can further augment and accelerate the liver’s natural capacity to regenerate itself,” said Günther Fürst, M.D., co-author and professor of radiology.

In the study, researchers compared the results of portal vein embolization (PVE), a technique currently used to help regenerate liver tissue, to a combination of PVE and an injection of bone marrow stem cells into the liver.

PVE blocks blood flow to the diseased portion of the liver and diverts blood to the organ’s healthy tissue, promoting liver growth. Bone marrow stem cells extracted from the patient’s hip bone and injected into the liver also help the liver regenerate.

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2006 Breast Cancer Showhouse Proceeds to Fund Three Studies and a Lab Grant, Totaling $500,000

The Wisconsin Breast Cancer Showhouse Board has awarded over $500,000 in grants to three Medical College of Wisconsin Cancer Center scientists to pursue promising research studies in breast and prostate cancer, and to endow a dedicated laboratory fund. The funds are proceeds of the 2006 Showhouse and related events.

“Generous sponsors, designers, volunteers, Showhouse owners and the strong support of the community have all contributed to the great success of these events,” says Board Chairman Katherine “Squeakie” Bruce. “Their dedication, energy and loyalty continue to grow each year, along with their hope of defeating these devastating diseases.”

“It is an honor to work with such dedicated volunteers, donors and designers, without whom we could not make these substantial contributions in support of outstanding local breast and prostate cancer research,” adds Showhouse co-chair Judy Simonitsch.

Showhouse members work not only to raise the funds, but also to determine their best use, which is done at an annual meeting held each January, according to interim Cancer Center Director Bruce Campbell, M.D., professor of otolaryngology at the Medical College.

“Local funding helps make these distinctive research projects possible, and relevant, in terms of potential for expanded exploration and ultimately clinical application,” says Dr. Campbell. “Seed grants from the Wisconsin Breast Cancer Showhouse position our researchers to compete for major federal research funding.”

The 2006 grant recipients, their award amounts and research projects are:

  • Guan Chen, M.D., Ph.D., professor of pharmacology & toxicology - $150,000, for a study to address the role of estrogen receptor protein in the progression of breast cancer. Early-stage breast cancers require estrogen and an estrogen receptor (ER) for proliferation. However, as the disease progresses the cancer cells no longer require estrogen for growth. They become invasive and resistant to anti-estrogens. This project will directly test the hypothesis that the loss of ER protein contributes to breast cancer invasion. If successful, it could provide a novel strategy for inhibiting breast cancer cell invasion.
  • Balaraman Kalyanaraman, Ph.D., chairman and professor of biophysics -$116,563, for study of a drug with the potential  to enhance the anti-tumor effect of doxorubicin, an antibiotic widely used in treatment of breast and other cancers, while reducing its heart-damaging side effects. Based on the recent discovery that doxorubicin kills tumor cells and cardiac cells by two different mechanisms, it may be possible to reduce the dangerous side effects of doxorubicin without affecting, and perhaps actually enhancing, the anticancer effect of the drug. Medical College researchers have already generated data suggesting that a single drug, Mito-Q, when combined with doxorubicin can accomplish both goals. This study will test the efficacy and safety of Mito-Q, in combination with doxorubicin, in an animal model.
  • Kasem Nithipatikom, Ph.D., associate professor, pharmacology and toxicology - $150,000, for studies to address the mechanism by which a naturally occurring acid (EET) stimulates the spread of prostate tumors. The project will focus on three mechanisms. First, to evaluate the role of oxygen deficiency in prostate cancer cells on EET regulation; second, to use molecular and pharmacological approaches to increase EET and address whether this promotes cancer cell proliferation and invasion; and third, to address EET–mediated signaling pathways that target the oxygen deficiency factor.
  • An additional $84,000 has been set aside for the Wisconsin Breast Cancer Showhouse Laboratory Fund at the Medical College. This fund will be used by a senior investigator to purchase equipment, set up unique laboratory initiatives and enhance care research facilities.
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Light-based probe 'sees' early cancers in first tests on human tissue

DURHAM, N.C. -- In its first laboratory tests on human tissue, a light-based probe built by researchers at Duke University's Pratt School of Engineering almost instantly detected the earliest signs of cancer in cells that line internal organs.

If the preliminary success of the "optical biopsy" is confirmed through clinical trials, such a device could ultimately provide a particular advantage for early diagnosis, treatment and prevention of many types of cancer, according to the researchers. The vast majority of cancers start in the body's epithelial cells, which line the mucous membranes in the lungs, esophagus and gut.

"About 85 percent of all cancers start in the epithelium. It may be, for example, brain cancer that causes a patient's death, but that cancer might have originated in the colon or other site of epithelial tissue," said Adam Wax, professor of biomedical engineering. "Being able to detect pre-cancer in epithelial tissues would therefore help prevent all types of cancer by catching it early, before it has a chance to develop further or spread."

In some instances, the technique, known as "fa/LCI" (frequency-domain angle-resolved low coherence interferometry), might ultimately enable doctors and their patients to avoid removal of tissue for biopsy, Wax said. In other instances, he added, fa/LCI could help physicians pinpoint suspicious cells during a traditional biopsy procedure, making it less likely for a cancerous lesion to escape detection.

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New 'biofuel cell' produces electricity from hydrogen in plain air

CHICAGO, March 26 —A pioneering “biofuel cell” that produces electricity from ordinary air spiked with small amounts of hydrogen offers significant potential as an inexpensive and renewable alternative to the costly platinum-based fuel cells that have dominated discussion about the “hydrogen economy” of the future, British scientists reported here today.

The research was presented at the week-long 233rd national meeting of the American Chemical Society, the world’s largest scientific society.

Fraser Armstrong, Ph.D., described how his research group at Oxford University built the biofuel cell with hydrogenases — enzymes from naturally occurring bacteria that use or oxidize hydrogen in their metabolism. The cell consists of two electrodes coated with the enzymes placed inside a container of ordinary air with 3 percent added hydrogen.

That is just below the 4 percent danger level at which hydrogen becomes an explosion hazard. The research established for the first time that it is possible to generate electricity from such low levels of hydrogen in air, Armstrong said.

Prototype versions of the cell produced enough electricity to power a wristwatch and other electronic devices. Armstrong foresees advanced versions of the device as potential power sources for an array of other electronic products that only require low amounts of power.

“The technology is immensely developable,” Armstrong said. “We are at the tip of a large iceberg, with important consequences for the future, but there is still much to do before this generation of enzyme-based fuel cells becomes commercially viable. The idea of electricity from hydrogen in air, using an oxygen-tolerant hydrogenase is new, although other scientists have been investigating enzymes as electrocatalysts for years. Most hydrogenases have fragile active sites that are destroyed by even traces of oxygen, but oxygen tolerant hydrogenases have evolved to resist attack.”

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