Across the Spectrum

Funded program highlights

VCU critical injury and illness research group lands $3.5 million in grants for research using blood substitute
The Office of Naval Research awarded $3.5 million in four grants to the VCU Reanimation Engineering Shock Center, VCURES, for research using the blood substitute Oxycyte in studies of decompression sickness, embolisms, traumatic brain injury and blast injuries.

VCURES is VCU’s critical injury and illness research group that specifically studies the delivery of oxygen. VCURES has generated approximately $35 million in research funding over an eight-year period in work that has a myriad of applications in areas as diverse as the military, homeland security, emergency medicine and traumatic brain injury.

Oxycyte is a perfluorocarbon therapeutic oxygen carrier and blood substitute.

“These grants will allow us to expand upon the previous studies that showed early intervention with Oxycyte can prevent the destruction of nerve cells and brain tissue in a number of conditions, including decompression illness and gas embolism,” said Bruce Spiess, M.D., VCU professor of anesthesiology and emergency medicine and director of VCURES.

The grants are as follows:

  • $1.2 million over three years will be used in ongoing studies of perfluorocarbon emulsions in the treatment of severe decompression sickness, or DCS. DCS occurs in divers and mine workers, at high altitudes and in space flight. It also is a potential complication of rescue from a disabled submarine. Previous VCURES work has demonstrated Oxycyte’s ability to significantly improve oxygen delivery to tissues and the increased removal of nitrogen from the body.
  • $1.6 million over three years will support research into Oxycyte’s ability to treat/prevent organ damage from arterial gas embolism, or AGE. AGE is a potential result of DCS but also occurs during a number of surgical procedures, including cardiac surgery, orthopedic joint replacement, gynecologic surgery and neurosurgery. 
  • $300,000 over two years will sponsor a postdoctoral candidate to work in the microcirculation laboratories of VCURES supporting research in AGE, DCS and other work in traumatic brain injury.
  • $300,000 will be used for pilot studies into the effectiveness of Oxycyte in treating traumatic brain injury secondary to a blast. Blast injury is the largest single cause of mortality and long-term morbidity for coalition troops stationed in Iraq and Afghanistan. VCURES already is working with Oxycyte and has shown it to be effective in treating traumatic brain injury from isolated blunt closed head injury and blast.

Jerome F. Strauss III, M.D., Ph.D., dean of VCU’s School of Medicine, said the grants “demonstrate the creativity of VCU investigators and our commitment to research that improves the care of critically ill patients.”

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Researcher awarded NCI grant to study effects of waterpipe smoking
A Virginia Commonwealth University psychology professor has received a National Cancer Institute grant totaling more than $2.8 million to study and identify toxins in waterpipe tobacco smoke — another potentially lethal form of tobacco use — and determine the extent to which waterpipe smokers are exposed to these toxins. 

In the past eight to 10 years, smoking tobacco with a waterpipe, also called a hookah or shisha, has grown in popularity in the U.S., especially among adults 18 to 24 years of age. The belief among some waterpipe users is that this method of smoking tobacco delivers less tar and nicotine than regular cigarette smoking and has fewer adverse health effects.

“Waterpipe tobacco smoking is a little-understood, but rapidly emerging strain in the nation’s tobacco use epidemic, and is becoming a growing public health concern,” said Thomas Eissenberg, Ph.D., associate professor in the VCU Department of Psychology and principal investigator on the grant. The grant also involves Alan Shihadeh, Ph.D., with the Department of Mechanical Engineering at American University of Beirut, in Beirut, Lebanon.

The five-year project will examine the effects of smoking waterpipe tobacco on the heart, lungs and cell biology in individual users by measuring their toxin exposure as well as the toxin content of waterpipe tobacco smoke. Secondly, Eissenberg and his team will study group waterpipe tobacco smoking in hookah cafes, again examining its effects and levels of toxin exposure and content. The team will compare effects, toxin exposure and content between waterpipe tobacco smoking and cigarette smoking.

“The information we gain through our study may help prevent future waterpipe use by providing evidence-based information to potential users, who are currently misled by product labeling that suggests that waterpipe use is associated with minimal nicotine and no tar,” said Eissenberg, director of the VCU Clinical Behavioral Pharmacology Laboratory and a researcher with the VCU Institute for Drug and Alcohol Studies.

In a hookah, tobacco is heated by charcoal and the resulting smoke is passed through a water-filled chamber, cooling the smoke before it reaches the smoker.

Waterpipes originated hundreds of years ago and were popular primarily among men in Southwest Asia and North Africa who used them to smoke tobacco in cafes. After falling out of favor, the popularity of hookahs started to increase again in the late 1990s and usage has spread to big cities and college towns in the U.S.

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NCI renewal grant to develop new cancer therapies
A VCU Massey Cancer Center research team has received a renewal grant totaling nearly $1.3 million from the National Cancer Institute to improve the activity of a novel class of agents, known as histone deacetylase inhibitors, in the treatment of leukemia and other blood malignancies.

Through the five-year grant, Steven Grant, M.D., Massey’s associate director for translational research and co-leader of the center’s Cancer Cell Biology Program, and his research team will focus efforts to support ongoing basic and clinical research.

Histone deacetylase inhibitors represent a diverse group of agents that modify the structure of chromatin and, by extension, genes involved in the control of death and differentiation in cancer cells. Chromatin houses the genome and is composed of DNA and scaffolding proteins, notably histones.

However, histone deacetylase inhibitors acetylate other proteins and exert multiple other effects that trigger apoptosis, or programmed cell death, in tumor cells. Acetylation is a chemical reaction that can change the molecular properties of certain proteins.

“Histone deacetylase inhibitors are currently the focus of intense interest as so-called ‘epigenetic agents,’ that is, agents that act by modulating gene expression,” said Grant, who is also the primary investigator for the project.

“Our goal is to exploit recent insights into the mode of action of these agents to make them even more effective in various hematologic malignancies by rationally combining them with other molecularly targeted agents,” he said.

Recently, histone deacetylase inhibitors have been approved for the treatment of patients with cutaneous T cell lymphoma, a type of cancer of the immune system. In previous work, Grant’s team has shown that histone deacetylase inhibitors induce acetylation and activation of a transcription factor, NF-kappaB, which regulates the expression of genes implicated in antioxidant defenses and cell survival.

According to Grant, the team has also identified agents that antagonize acetylation and activation of NF-kappaB by histone deacetylase inhibitors, resulting in a dramatic increase in oxidative injury and lethality. Such agents include inhibitors of IKK-beta and a class of agents known as proteasome inhibitors. Further, proteasome inhibitors have already proven very active in multiple myeloma and certain types of lymphoma.

“Our goal is to elucidate the mechanisms by which such agents increase histone deacetylase inhibitor activity against leukemia and related malignancies,” Grant said.

“We can then utilize this information as a platform to develop novel combination regimens incorporating histone deacetylase inhibitors and NF-kappaB antagonists such as proteasome and IKK-beta inhibitors in the treatment of acute leukemia and other hematologic malignancies.” 

Grant and his team are already leading a multi-institutional trial of vorinostat, a histone deacetylase inhibitor, in combination with flavopiridol, a cell cycle inhibitor, in patients with refractory acute leukemia or myelodysplastic syndrome.

Additionally, the team recently received approval to lead a multi-institutional trial of vorinostat and bortezomib, a proteasome inhibitor, in patients with refractory diffuse lymphocytic B-cell lymphoma or mantle cell lymphoma.

Investigators from the VCU School of Medicine, Paul Dent, Ph.D., Mohamed Rahmani, Ph.D., Yun Dai, Ph.D., Roberto Rosato, Ph.D., and Viswanathan Ramakrishnan, Ph.D., collaborate with Grant on this work.

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VCU awarded $1.2 million grant to help content-area teachers of English language learners

VCU has received a federal grant to train content-area teachers to effectively teach English language learners in the middle and high schools of Chesterfield County, Va.

The five-year, $1.2 million national professional development grant from the U.S. Department of Education will help provide high-quality, focused and sustained training programs that will increase English language learners’ academic achievements.

With more than 58,000 students, Chesterfield County Public Schools is the fourth-largest school system in Virginia and one of the 100 largest school systems in the country. The number of English language learning students there has grown from 400 in 1998 to 2,200 — an increase of more than 500 percent. These students are predominantly from Spanish-speaking countries, such as El Salvador, Guatemala, Mexico and Colombia, but also come from Cambodia, Vietnam, Korea or Arab-speaking countries.

Virginia requires all English language learners to take state Standards of Learning tests after their first year. Although they are meeting state benchmarks in reading and math, pass rates for English language learners in Chesterfield are lower than the county's overall pass rates: 83 percent of all students and 76 percent of English language learning students passed their math SOL test; 90 percent of all students and 75 percent of English language learners passed their language arts SOL test; and 91 percent of all students and 77 percent of English language learners passed their science SOL test.

“Closing the achievement gaps for English language learning students is vital,” said Terry Franson, English for Speakers of Other Languages instructional specialist for Chesterfield County Public Schools. “This grant program will make a great difference in the lives of students who come to us in middle and high school with limited English skills. Working together, content area teachers and ESOL teachers will help students achieve academic success.”

“It seems insurmountable for English language learners to meet the grade-level standards in such a short period of time, particularly without special assistance from appropriately trained content-area teachers,” said grant director Seonhee Cho, Ph.D., an assistant professor in the VCU School of Education who specializes in ESOL education. “What is more challenging for secondary English language learners is the depth and breadth of content knowledge and discipline-specific and cognitively demanding academic language compared to their younger, elementary counterparts.”

Research shows that English language learners can learn better and faster when English instruction is combined with content than they can in language-only classes.

“Thus, the role of content-area teachers is critical in English language learners’ academic success,” said Cho.

The grant project will provide services and activities largely in three areas: summer institutes, follow-ups with technical assistance and building of professional learning communities.

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VCU Massey Cancer Center to partner with Israeli biotech firm on $1 million pancreatic cancer clinical research study
The VCU Massey Cancer Center will open a Phase I pancreatic cancer study later this year in conjunction with leading researchers from Israel, marking the first time cancer researchers at VCU have partnered with their counterparts in Israel.

The study is supported by a $950,000 grant from the U.S.-Israel Bi-National Industrial Research and Development Foundation (BIRDF). Leaders from the Virginia Israel Bioscience Commercialization Center (VIBCC) helped to foster Israeli interest in research at VCU.

The clinical trial, designed by Massey principal investigator Ray Lee, M.D., Ph.D., involves a novel targeted therapeutic agent developed by BioCancell of Jerusalem and will offer new hope for one of the most difficult-to-treat cancers.

“This collaboration is a tangible outcome of the initiative launched by the Virginia BioTechnology Research Park more than a year ago to recruit Israeli life science companies with innovative products and technologies to Virginia and the Research Park,” said Robert T. Skunda, President and CEO of the research park.

“The world, indeed, is getting flatter,” said Donna Edmonds, executive director of the Virginia Israel Bioscience Commercialization Center. “By importing and exporting high-quality medical research and building collaborative clinical studies such as this, we can work toward saving more lives of people with cancer in Virginia and across the globe.”

Gordon D. Ginder, M.D., director of the VCU Massey Cancer Center, said, “Having an organization dedicated to promoting Virginia’s academic, clinical and biotechnological expertise is a boon to the commonwealth. As federal funding for cancer research in the U.S. has shrunken in the face of expanding scientific opportunities for better treatment and prevention, it’s vital that we explore international collaborations and funding sources, too. We are grateful to the VIBCC for serving as a beacon to guide international funding and research opportunities to us.”

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