California State University, Long Beach Scientists Receive $2.6 Million Grant from the National Institute of General Medical Sciences

A four-year grant worth more than $2.6 million for science research has been awarded to six Cal State Long Beach faculty members by the National Institute of General Medical Sciences (NIGMS), one of the National Institutes of Health (NIH), according to CSULB President Robert C. Maxson.

Approximately $344,000 of the grant is being used to establish a Support of Continuous Research Excellence (SCORE) program funded by NIGMS' Minority Biomedical Research Support branch, said Professor Laura Kingsford, chair of the Biological Sciences Department and SCORE program director. In addition, five faculty members will work with undergraduate and graduate students on research that has biomedical applications. The research projects cover a variety of topics:

Iron is often thought of as something tough, but it is considered a transitional metal at the atomic level, giving it properties that are valuable in both chemistry and biology. CSULB Professor Lijuan Li, who specializes in inorganic chemistry, organometallics and transitional metals, is collaborating with Professor Peter C. Ford of UC Santa Barbara on a $551,000 study focusing on biological applications of iron compounds in generating and controlling nitric oxide.

"Ten or 15 years ago, nitric oxide was considered a very bad molecule-responsible for L.A. smog, acid rain, an environmental pollutant, a toxic radical," said Li. "But in the last 10 years or so, biologists have found that nitric oxide actually exists in the human body in very small concentrations. It's responsible for long-term memory, controls clot aggregation and blood pressure and can kill microorganisms. Because nitric oxide is so important, there is a great need in the scientific society to have a compound that can release it. There are many applications. You can directly use it as a cardiovascular relaxing agent. You can use it to control cancer or tumor growth," she explained.

"Nitric oxide activity in chemistry and biology is not yet fully discovered. Biologists who want to study how nitric oxide works in different systems need some kind of model compound to release nitric oxide to help them do their pharmacokinetic studies" on how the body uses drugs, said Li.

Pharmaceutical firms have a major interest in such results for developing heart, blood pressure or cancer medications. Even Viagra was the result of nitric oxide studies.

The SCORE project focuses on isolating non-heme iron nitrosyl compounds, which is iron bonded
to nitric oxide. Non-heme iron, absorbed from food, does not bind with oxygen. "These type of molecules are responsible for cardiovascular relaxation. There are possibilities that these types of iron nitrosyls are acting as nitric oxide stores," said Li.

Biological Sciences Professor Kay Lee-Fruman is using her $474,000 SCORE funding to look at a protein, or kinase, called SK62.

"I'm interested in this protein because it has some applications in immunology," she said. Part of her work involves studying how SK62 might be regulated by a drug called rapamycin. "People found that what was happening inside the cell once the drug is administered is that it inhibits the activity of a kinase called p70. It became more evident that it may not be the only reason why rapamycin has its immunosuppressing activity, so people are looking for other kinases that look similar or that might be regulated by the same drug. Our protein, S6K2, is one of those. We are looking for the function of this protein to see whether it has any importance in immune cell function or any cell function."

Another aspect will examine white blood cell division, with implications in the understanding of cancers of the bloodstream such as leukemia and lymphoma.

There might not appear to be a connection between goby fishes and medicine, but the studies that Biological Sciences Professor Raymond R. Wilson is conducting with his $480,000 in funding has implications for understanding how invasive species, including human pathogens, can spread among natural populations.

"I'm studying the mitochondrial DNA and nuclear genetics of two California populations of yellowfin gobies together with a native population in China," Wilson explained. The gobies are native to Asian waters, but not to California estuarine regions where they are now found, so it's believed that the fish were brought over in merchant shipping ballast water sometime in the early 20th century.

"The work is centered around looking at population genetic changes in relation to the amount of time since the invasion occurred. We have a specific prediction of what the frequency distribution of these mitochondrial sequences should look like in data from recent invaders, so we're going to test that prediction with gobies that we know are recent invaders," said Wilson.

"If this model appears to hold up in this case, then it will be potentially a very powerful model to apply in cases when we don't know the temporal history of an invasion. When we finish in four years, we should know what the population genetics of a recent invasive species looks like in detail. We'll also know if the invasion is happening on a continuing basis. We will hopefully be the place in the country that has created the most thorough data model system for looking at invasive species in marine estuarine systems."

Wilson said the NIH is interested in his fish study because "we propose that we can develop a
genetic indicator of the relative recency of invasion. In the field of epidemiology, for example, if foreign pathogens were coming into a system one might be able to use our model for that application. One might be able to take a relatively small amount of genetic data from the invasive pathogen to determine if it's been here for only a few years, if it's isolated or not, or if it's continuing to receive fresh immigration."

Other recipients include Biological Sciences Professor Editte Gharakhanian, who received $483,000 to study protein trafficking and delivery to the lysosomal vacuole of the bread yeast. Analogous to the mammalian lysosome, the yeast vacuole is the cellular organelle responsible for degradation of macromolecules such as proteins as well as in breakdown of toxins. Her work will help further define genes, gene products, and the cellular machinery involved in delivering the enzymes responsible for degradation to the lysosome. Mislocalization of lysosomal proteins are involved in many forms of cancer and in lysosomal storage diseases.

Chemistry/Biochemistry Professor Marco A. Lopez received $240,000 to study the interaction of chemicals called imidazoles with molecules called hemes, and how these imidazole-heme systems interact with dioxygen, carbon monoxide, and nitric oxide (gaseous ligands). Imidazole-heme systems are studied as models of hemeproteins.

The goal of these studies is to learn the details of how these models of hemeproteins interact with gaseous ligands. Potential applications of these studies are in the field of sickle-cell anemia, the preparation of blood substitutes, and learning more of how nitric oxide carries out its many newly-discovered processes. The journal Science named nitric oxide "molecule of the year" for 1992. The 1998 Nobel Prize in Medicine was awarded for work on showing that nitric oxide is an important signaling compound that helps the body regulate key functions such as blood pressure and preventing blood clots that can cause strokes.