Five UT Health Science Center at Tyler researchers awarded more than $1.2 million in grants

Tuesday, September 30, 2008

Five biomedical researchers at The University of Texas Health Science Center at Tyler recently were awarded grants totaling more than $1.2 million.

They are Murty Madiraju, Ph.D., professor of biochemistry; Hua Tang, Ph.D., associate professor of biochemistry; Steven Idell, MD, Ph.D., vice president for research at UTHSCT; Ramakrishna Vankayalapati, Ph.D., associate professor of microbiology and immunology; and Sharmila Shankar, Ph.D., assistant professor of biochemistry.

With more than $12 million in annual research spending in fiscal year 2008, UTHSCT scientists direct world-class programs investigating lung disease, cancer, tuberculosis, diabetes, and aging.

UTHSCT was awarded 61 grants and National Institutes of Health funding of over $5.2 million in FY 2008, which ended Aug. 31.

Murty Madiraju, Ph.D.
Dr. Madiraju received a one-year, $351,042 bridge grant from the National Institutes of Health to continue his investigation of how tuberculosis bacteria duplicate their DNA.

The National Institute of Allergy and Infectious Diseases, part of NIH, has funded Dr. Madiraju’s TB research for the past several years. He is in the process of applying for future NIH grant funding.

“Without the faithful duplication of DNA, the bacteria cannot multiply. This research is important, because a defect in this process will prevent the TB bacteria from increasing and the disease from progressing,” Dr. Madiraju said.

Tuberculosis is a major cause of illness and death worldwide, especially in Asia and Africa, according to the World Health Organization.

TB infects one-third of the world’s population and causes almost 2 million deaths per year.

TB bacteria are able to lodge in the lungs, where they can multiply and evade the initial attacks of the human immune system, Dr. Madiraju said.

During later stages of infection, the immune system mounts serious assaults on the bacteria, preventing them from multiplying and spreading.

However, when the immune system weakens because of age or other diseases, the bacteria are able to multiply and cause active tuberculosis, he said.

“This NIH grant supports our research into how the machinery of TB replication is regulated. This knowledge will be critical for developing new drugs to control tuberculosis infections,” he said.

The research is being conducted in collaboration with Malini Rajagopalan, Ph.D., professor of biochemistry at UTHSCT.

Hua Tang, Ph.D.
Dr. Tang received a two-year, $140,000 grant from the American Heart Association to study how inflammation in blood vessel walls is regulated by a specific group of enzymes called protein kinase D family kinases.

“Inflammation in blood vessel walls plays a central role in the development of various cardiovascular diseases. Our research will help us understand how these enzymes regulate the production of the cells that line the blood vessels and the release of inflammatory agents called cytokines,” Dr. Tang said.

He and his team are probing the underlying mechanisms behind this vascular inflammation, which is associated with diseases such as atherosclerosis, or hardening of the arteries.

“Once we understand more about how these enzymes regulate inflammation in blood vessel walls, we can develop new therapies that protect against inflammation and so prevent cardiovascular disease,” Dr. Tang said.

Steven Idell, MD, Ph.D.
Dr. Idell received $50,000 from The University of Texas System to support the manufacture and commercialization of scuPA, a drug that clears scarring in the pleural space – the area between the lungs and the inside of the chest wall.

Pleural scarring from pneumonia affects about 80,000 Americans each year.

“We are raising funds to bring scuPA to clinical trials, because our published research shows it may work better than surgery or other currently available drugs used to treat this condition,” Dr. Idell said.

Ramakrishna Vankayalapati, Ph.D.
Dr. Vankayalapati was awarded a two-year, $368,750 NIH grant to investigate how certain kinds of immune cells found in the blood – regulatory T cells – inhibit the immune system’s response against tuberculosis bacteria in infected individuals.

Because tuberculosis affects so many people worldwide, developing a more effective vaccine would be a tremendous public health breakthrough that would greatly reduce illness and death caused by TB, he said.

While 90 percent of people infected with TB bacteria have immune systems that protect them from the disease, 10 percent either quickly come down with TB or develop it many years later, when their immune systems are weakened through age or other diseases, Dr. Vankayalapati said.

“We will describe and examine the mechanisms by which regulatory T cells inhibit good immune responses in infected individuals,” he said.

“This research is important because it will help us devise ways to improve the protective immune response and develop an effective vaccine against tuberculosis,” Dr. Vankayalapati said.

“Although TB is not common in East Texas, it is relatively common in immigrants from countries with a high incidence of the disease. If we better understand the immune response to tuberculosis, we can use this knowledge to develop vaccines against other diseases that are more common in the United States, such as HIV and hepatitis C,” he said.

Sharmilla Shankar, Ph.D.
Dr. Shankar received a three-year, $300,000 grant from the Susan G. Komen Foundation to explore how some molecules bind to so-called “death receptors” on the surface of cancer cells and force them to die.

While many initial breast cancers depend on the hormone estrogen to grow and spread, when breast cancer reoccurs it’s usually in the form of tumors that don’t need estrogen to thrive, she said.

Cutting off the flow of estrogen won’t shrink these tumors.

“Another challenge in treating breast cancer is how toxic many anti-cancer drugs are to normal organs and tissues. To improve cancer patients’ outcomes, we need new therapies that kill cancer cells irrespective of their estrogen, progesterone, and Her-2 neu status,” Dr. Shankar said.

Her-2 neu is a gene that plays a role in the development of breast cancer.

One such approach is to target tumors with new compounds that bind to death receptors on the cancer cells, she said.

These compounds attach to the receptors on the surface of the cell and signal the cell to die. Normal cells don’t have the same kind of receptors, so the compounds don’t bind to the normal cells.

“Through our research, we hope to identify and develop more effective and less toxic drugs to treat human breast cancer. The results of our investigations will provide a foundation for new therapeutic strategies to treat breast cancer,” she said.

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