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Young Investigators Recognized for Promising Research Projects

Published: January 08, 2009 by

On Nov. 18, The University of Texas Health Science Center at Houston honored six assistant professors whose innovative work shows great promise for future breakthroughs in basic science and clinical care. The goal of the Fourth Annual Young Investigators Appreciation Luncheon was to recognize the achievements of these young investigators and foster diverse and collaborative research programs at the health science center. "I am delighted to be here to honor these young investigators, seeing how distinguished they really are," said Larry R. Kaiser, M.D., president of The UT Health Science Center at Houston. "I hope to be able to create an environment where we encourage and recognize the careers of young investigators. So much of the success of the institution is based on outstanding young investigators." The following researchers were nominated by their schools and selected by the Research Council as outstanding representatives of the many hard-working young investigators throughout the UT Health Science Center.

Rebecca Casarez, Ph.D., R.N.

Rebecca Casarez, Ph.D., R.N.

Study connects spirituality and management of chronic illness

Rebecca Casarez, Ph.D., R.N.

assistant professor of integrative nursing care, School of Nursing

The effects from a chronic illness can be burdensome to patients, depriving them of their independence and lessening their quality of life. A chronic illness may cause some patients to feel of depressed and hopeless, while they yearn for ways to cope with their illness.

Spirituality may be the answer for some patients with a chronic illness.

Rebecca Casarez, Ph.D., R.N., has worked for many years as a nurse, caring for those with a chronic illness.

"I believe that, for some people, spirituality may be a way to help them cope with the physical limitations of their disease," she said.

Casarez and her colleague, Evangelina Villagomez, Ph.D., are working on a pilot project to develop a spiritually and culturally based diabetes self-management curriculum for African Americans with diabetes. By working with an advisory committee of African Americans in a local church, Casarez and Villagomez conduct group interviews with research participants.

Current statistics from the American Diabetes Association state that 3.7 million or 14.7 percent of all African Americans ages 20 years or older have diabetes, and African Americans are 1.6 times more likely to have diabetes as non-Hispanic whites.

"I have found that, for many of the African Americans I have interviewed, spirituality does affect how they take care of their diabetes," Casarez said. "Many have told me they have a relationship with God, which gives them strength to manage their illness."

Performing spiritual practices - praying, reading Scriptures and listening to spiritual music - also contributes to better self-care for managing diabetes, according to Casarez.

"Some of the participants have told me that prayer gives them determination to follow their self-management practices, keeps them focused and helps stabilize their blood sugar levels," Casarez explained. "For some, the Bible offers advice from specific Scriptures on how to take care of their health. Also, listening to Christian radio may be a distraction from unhealthy behaviors (such as eating too much), and church attendance may provide opportunities to hear teachings about taking care of the body."

Once Casarez and Villagomez compile the data from their pilot project, the next step is to obtain funding to test the effectiveness of a diabetes self-management program for African Americans that includes spirituality.

"We hope that after the participants receive this program that their blood glucose levels will improve," Casarez said of her future project. "If their blood glucose levels are kept within normal limits over time, they are less likely to experience the long-term complications of diabetes (blindness, kidney failure, leg amputations and heart disease) and will live a longer life."

Danielle Garsin, Ph.D.

Danielle Garsin, Ph.D.

Worms could unearth secrets of host-pathogen interaction

Danielle Garsin, Ph.D.

assistant professor of microbiology and molecular genetics, Medical School

Infectious bacteria are becoming smarter than the drugs used to kill them. This rise in antibiotic-resistant infections represents a growing public health problem whereby diseases are becoming untreatable with the antibiotics once used to cure them.

Research by Danielle Garsin, Ph.D., focuses on strategies to keep infectious diseases under control. Specifically, she studies host-pathogen interactions to understand the factors that allow a bacterial pathogen to cause disease and those that are important for host defense.

Her experiments involve a tiny worm called Caenorhabditis elegans (C. elegans) and a human bacterial pathogen called Enterococcus faecalis (E. faecalis).

"When feeding on E. faecalis, this little worm becomes sick and dies," Garsin said. "Both the bug and the worm can be genetically manipulated, and this allows us to identify the factors involved in the hostpathogen interaction. Specifically, we are looking for the genes that make E. faecalis able to cause disease and the genes in the worm that contribute to an effective defense against infection. The hope is that what we learn in this model system will give us ideas and strategies that can be applied to clinical infectious disease."

Garsin's laboratory has discovered that the worm's intestinal cells release toxic molecules called reactive oxygen species in response to infection, and her ongoing research looks to connect this finding to humans.

"There is evidence that the cells that line our intestine and other mucosal surfaces might do the same thing, but how this works and the importance in defense against infection is not well understood," she said. "Our ongoing studies are focused on understanding this process."

Garsin also has identified genes that allow E. faecalis to be an effective pathogen, while work continues to understand their role in causing disease. "I have always been fascinated by how ‘life' works," Garsin said. "Identifying the factors that allow bacterial pathogens to cause disease will potentially lead to new targets for antimicrobial drug design, and understanding what constitutes a beneficial immune response will potentially allow us to manipulate the immune response to our advantage."

D. Michael Hallman, Ph.D.

D. Michael Hallman, Ph.D.

Genetic changes from adolescence to adulthood may predict disease risk factors

D. Michael Hallman, Ph.D.

assistant professor of human genetics, School of Public Health

Do the genes we inherit at birth predispose us to develop heart disease?

Do our genes increase or decrease our chances of developing complications from diabetes?

Do the effects of some genes change as we grow older?

Finding the answers to questions about the genetics of cardiovascular disease and type 2 diabetes is at the core of research by D. Michael Hallman, Ph.D. One project he works on focuses on examining the genetics of cardiovascular disease risk factors, including high cholesterol levels.

"I have a particular interest in genetic factors that affect changes in lipid levels with age, from childhood through adolescence and into adulthood," Hallman said. "For example, few children have high cholesterol levels, but many adults do. Relatively little is known about possible changes in gene effects with age, as there are few studies that have been able to measure cardiovascular disease risk factors periodically in large groups of individuals as they age from childhood and into adulthood."

Hallman is working with data collected from two studies, Project HeartBeat! and the Bogalusa Heart Study, that measured the traits related to cardiovascular disease in school-aged children.

Project HeartBeat! involved children, ages 8-18 years, from The Woodlands and Conroe, who were measured up to three times annually over a four-year period.

"We're measuring variants in selected genes involved in blood pressure or changes in height, weight and body fat, in order to try to identify variants that affect changes in these traits over time," Hallman explained.

The Bogalusa Heart Study measured cholesterol levels, blood pressure and other cardiovascular disease risk factors in children living in Bogalusa, La., every three years from the 1970s to the 1990s. Eventually, Hallman says, this study developed into a longitudinal study of the changes that occur with age in traits related to cardiovascular disease, with individuals ranging from 5-38 years of age.

"In earlier work on the Bogalusa Heart Study sample, we investigated several genes involved in regulating the levels of cholesterol and other blood lipids, finding one case where the effect of a particular gene in raising high density-lipoprotein cholesterol (the "good" cholesterol) did not appear until adolescence," Hallman said.

A second project Hallman investigates is the genetics of type 2 diabetes and its complications, particularly diabetic retinopathy, which is a leading cause of blindness in adults. Examining genetic data from Mexican Americans with type 2 diabetes led Hallman to an important finding.

"We have helped establish that genes appear to be more likely to affect the development of severe diabetic retinopathy than milder forms - that is, a tendency to develop more severe diabetic retinopathy may run in families, while almost anyone who has diabetes long enough may develop at least mild retinopathy," Hallman explained.

Hallman said he hopes his research will lead to a better understanding of the genetic factors that affect cardiovascular disease and complications resulting from type 2 diabetes.

"We know from years of work that there probably aren't going to be any common genetic variants in the population that have large effects on these conditions at an individual level, though some genetic mutations are common enough in the population to have modest risk-raising effects in large numbers of people," he said. "I hope my work can contribute to our knowledge of the genetic factors that affect the physiological changes that occur at puberty and with later aging."

Jianping Jin, Ph.D.

Jianping Jin, Ph.D.

Ubiquitin signaling pathway hoped to lead to cancer cure

Jianping Jin, Ph.D.

assistant professor of biochemistry and molecular biology, Medical School

Our cells are in constant motion - creating proteins when needed and then destroying them when their job is done. While the cell must be selective at destroying proteins that are no longer needed, too many unwanted proteins can be toxic to our bodies.

Ubiquitin is a small protein that helps the cell with this process. It acts like a tag and attaches itself to unwanted proteins to signal their destruction.

"For example, when our skin is exposed to sunshine, our skin cells will respond to ultraviolet (UV) signals and trigger some protein degradation in order to protect our genome stability," said Jianping Jin, Ph.D.

Jin studies the ubiquitin signaling pathway toward the greater goal of cancer research. Research shows the accumulation of unwanted proteins, while toxic to the human body, has been linked to numerous diseases, such as cancer.

"We study how DNA damage response controls the degradation of Cdt1, a key DNA replication licensing factor, through the ubiquitin signaling pathway," he said. "We also study the basic mechanism regulating a newly discovered ubiquitin signaling pathway that is initiated by a new gene, called Uba6, which is an essential gene for development."

Jin combines biochemical and genetic methods to identify new components in the Uba6-dependent ubiquitin signaling pathway.

"We also try to understand how modification of Cdt1 affects its degradation under UV stress through genome-wide loss-of-function screen," he adds. "We believe Cdt1 degradation under UV stress is controlled by both ubiquitination and phosphorylation. Previously, we identified the ubiquitin ligase to ubiquitinate Cdt1 and triggered the degradation of Cdt1. Now, we have evidence to support multiple kinases and phosphatases involved in the whole process."

Jin says he hopes his work will lead to the discovery of essential genes that control the Uba6-dependent ubiquitin signaling pathway, while gaining insight into this essential signaling process.

"We are on the way to identify kinases and phosphatases, which regulate the ubiquitination of Cdt1 under DNA damage response, in order to better understand how our cells respond to DNA damage stress, such as UV and other genomic toxins," he said. "Cancer is a major human disease. I really hope my research can be translated into clinical meaning and help kill cancer in the future."

Michael Lorenz, Ph.D.

Michael Lorenz, Ph.D.

Study of the body's own fungi could lead to better drugs to fight infection

Michael Lorenz, Ph.D.

assistant professor of microbiology and molecular genetics, Medical School

Viruses, bacteria and fungi live everywhere. They inhabit the air we breathe, the food we eat and the water we drink. So naturally, countless microbes live outside and within our bodies. The immune system works tirelessly to protect us against harmful microbes, all the while creating a harmonious balance between beneficial microbes and those that are harmful.

Most humans have Candida albicans, a fungus that lives on the skin, mouth, intestinal tract and vagina. However, when our immune systems are weakened by illness, Candida becomes harmful. It can cause a variety of common fungal infections in humans, including oral thrush and vaginal yeast infections.

More importantly, Candida can cause serious bloodstream infections. "Bloodstream infections affect mostly debilitated patients, such as those with cancer, who are undergoing chemotherapy, have recently had an organ transplant, or who have implanted medical devices, such as artificial heart valves or even simply have an intravenous catheter," said Michael Lorenz, Ph.D.

Lorenz studies the relationship between Candida and the immune system with the goal of identifying better ways to treat patients who are at risk of acquiring an infectious disease.

"Our interest is in how the fungi evade our immune systems to cause disease in people, and we do this using a combination of molecular genetics, genomics, tissue culture and animal studies," he explained.

It is estimated that 10 percent of bloodstream infections that patients acquire in a hospital are from Candida. Lorenz said that, unfortunately, there are few good drugs on the market to treat fungal infections.

"We do a very poor job of treating these infections, and about four in 10 patients who get invasive candidiasis will die from it," he said. "With most infectious microbes, we can work to prevent the spread of the disease through hygiene and other measures to limit transmission from person-to-person. We can't do that with Candida because patients get the disease from themselves."

Mixing immune cells and Candida cells together in the laboratory and then monitoring how both cells interact has led Lorenz to important findings.

"We have identified that a primary response of Candida on contact with the immune system is to reorganize its cellular physiology," Lorenz said. "We also are showing that Candida can manipulate the immune cell, weakening its function in very specific ways."

Lorenz's findings have biological and clinical outcomes. Namely, he sees the potential for improvements in drug therapies for patients.

"Our findings are interesting from a biological perspective because it shows how this fungal pathogen has adapted to living inside of us in very complex and unexpected ways," Lorenz said. "From a clinical perspective, many of the processes we have identified are fungal-specific; that is, the enzymes and pathways exist in fungi (and other microbes) but not in mammals. Thus, there is great potential here for drug development."

Muhammad Walji, Ph.D.

Muhammad Walji, Ph.D.

Presentation can help patients understand, comply with instructions

Muhammad Walji, Ph.D.

assistant professor of diagnostic sciences, Dental Branch

Studying how health information is presented to patients and providers guided Muhammad Walji, Ph.D., toward an important finding.

Walji, whose research projects focus on the emerging field of health informatics, found that if health and medical information is presented effectively and persuasively, it can drastically change the attitudes and behaviors of patients.

"For example, we were able to reduce the number of missed clinic appointments by simply changing the words and increasing the persuasiveness in an automated appointment reminder message," Walji explained.

Health informatics is the study of how data is collected, stored, communicated and presented in order to improve health care. Walji's work focuses on the use of technology to enhance the way health information is conveyed to patients and providers.

Because the field of health informatics is so broad, Walji is able to apply his expertise to three different projects.

"I am working on a project to improve home oral health hygiene through a "Persuasive Toothbrush" that can track and monitor brushing habits automatically," Walji said. "I also study the quality of online health information to determine how patients may use what they find online to make decisions. I also work on human-computer interaction research such as how to improve the usability of health information systems in order to improve patient care."

Walji has found that the way health information is presented online is misleading and that many Web sites may be harmful.

Additionally, his research shows that expensive health information technology systems, such as electronic health records, are not well designed.

"Poorly designed systems may make it harder for health care providers (dentists, doctors, nurses, etc.) to do their jobs efficiently and may sometimes even increase medical errors," Walji explained. "I hope that our human-computer interaction and usability research will lead to better designed systems that can improve the delivery and quality of patient care."

Walji's work has the potential of helping patients make better and informed decisions about their own care.

"By understanding how to persuasively present information to patients through technology, I hope that our research will help to improve adherence to recommended and beneficial behaviors, such as improving oral hygiene, taking medications and/or increasing physical activity levels," he said.