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Annual Report - 2007-2008 - Research

Annual Report - Winter 2009

Momentum in Basic Science and Translational Research

Detecting Mechanisms and Markers
Profile: Biostatistician Makes Waves
Profile: Patience and Curiosity Lead Young Researcher to Breakthrough Discovery
Profile: Dream Setting, Dream Job for Researcher
Renowned Leader for Bioinformatics, Computational Biology
New Building Expands Research Opportunities
New Partnerships Spur Drug Development
P53 Presents a Different Face
‘The Three Musketeers of Cancer’ Ambush a Tumor Suppressor
Enzyme Active in Drug Resistance and Metastasis
Pulmonary Aerosol Tackles Deadly Infections
Connecting Diet and Cancer Pathways
Immunology – A Unique Combination Ignites Immune Response Usually Aimed at Fighting Infection

Detecting Mechanisms and Markers

New research approaches at MD Anderson focus on the human genome and the regulation of gene expression. Scientists identify and study particular genes and proteins that play a role in tumor growth or suppression, and they investigate the molecular mechanisms that account for the effects of these abnormal genes and their products. They collaborate in developing new targeted therapies to counteract the growth and survival of cancer cells, and they find ways to starve them of a blood supply and growth-promoting factors. They also investigate how to elicit immune responses to ward off and destroy cancer cells, and they use diagnostic imaging to determine abnormal molecules and activities in the cancer. The aim in each case is to translate that research to the patient.

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Biostatistician Makes Waves

By Mary Brolley

Jeffrey Morris, Ph.D.

His creation of a novel statistical method to capture and interpret biological data has made researchers all over the world take note.

In 2003, Morris, Ph.D., associate professor in the Department of Biostatistics and Applied Mathematics, wrote a scientific paper explaining how a wavelet-based statistical modeling method had yielded biological insights into colon carcinogenesis, the process by which normal cells are transformed into cancer cells.

The paper won his research group two major awards. And soon after its publication, Morris started hearing from researchers in many countries who were eager to adapt his method to their research.

The primary focus of Morris’ methodological research involves developing statistical methods for analyzing functional and image data, and for evaluating various types of data encountered in bioinformatics. These new models have helped users of the latest high-throughput technologies — those that can analyze or produce information at a high rate of speed — extract more information from their data.

In addition, he collaborates with researchers at MD Anderson on various research projects, most involving gastrointestinal cancers. Besides designing studies and analyzing data, he tries to help them see other questions that can be addressed by the data they have collected.

Named an MD Anderson Faculty Scholar in 2004, Morris also received the Gottfried E. Noether Young Scholar Award from the American Statistical Association in 2005.

And he is still “tweaking and expanding” the methods he has developed — for example, to handle image data — as researchers around the world continue to ask for his help.

“I’m always thinking about ways to make it flexible enough for many applications and accessible to as many users as possible. I want my research to have an impact,” he says, then pauses. “I’m confident that it’ll have a long-term impact.”

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Patience and Curiosity Lead Young Researcher to Breakthrough Discovery

By Sandi Stromberg

Sendurai Mani, Ph.D.

Growing up in a small village in South India, Sendurai Mani had an insatiable curiosity.

From his grandmother, he learned about local medicinal plants. Then, while working on his master’s degree at Madurai Kamaraj University in Madurai, India, he remembered one plant whose extract was deadly. His hunch to work with his professor, patiently testing it for anti-cancer activity, led to his first exciting discovery and set him on his path toward a Ph.D. at the Indian Institute of Science in Bangalore, India.

It was there in 1998 that he met Robert Weinberg, Ph.D., a founding member of the Whitehead Institute and professor at Massachusetts Institute of Technology. Weinberg invited him to join his lab and to choose an area of study. Mani chose metastasis.

“The first lesson I learned in that lab was the importance of collaboration, that team efforts allow research to advance more quickly,” says Mani, assistant professor in the Department of Molecular Pathology.

With a colleague, he set out to answer the question: What makes a non-metastatic, square and stuck cancer cell become a spindly, mobile and metastatic one. After years of patient and collaborative work, they found that by switching on any one of three genes — called Twist, Snail and FOXC2 — they could force cancer cells in a petri dish to undergo the square-to-spindly shift, making them far more capable of initiating new tumors.

When Mani took this one step further by using healthy cells, he found the cells appeared to take on properties of stem cells, including the ability to make vast numbers of copies of themselves. On the basis of this breakthrough discovery and his novel strategy for using an innovative lineage-tracing mouse model, the Jimmy V Foundation recently named him a V-Scholar. This two-year award recognizes talented young cancer researchers, enabling them to quickly establish their laboratories and gain a competitive edge.

Mani hopes that his future research will help scientists understand the biology of cancer metastasis and ultimately lead to the development of interventions to target and destroy cells with metastatic potential that cause cancer to spread and lead to the majority of cancer deaths.

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Dream Setting, Dream Job for Researcher

By Mary Brolley

Karen Vasquez, Ph.D.

Some days, when she looks up from her work to see a deer or a rabbit wandering through her stretch of the piney woods, Karen Vasquez can’t believe her good fortune.

Sure, Vasquez, Ph.D., has plenty of responsibilities as associate professor, supervising 11 researchers intent on finding new targets for cures for cancer. But following her calling in such an idyllic setting — the Department of Carcinogenesis at MD Anderson’s Science Park- Research Division near Smithville, Texas — is a dream come true for Vasquez.

She first visited the Smithville facility as a graduate student, attending a Lost Pines Molecular Biology Conference, and thought, “How could anyone be lucky enough to actually work here?”

In her graduate research, Vasquez “became fascinated with DNA structure and the mechanisms of DNA repair,” especially as they affect carcinogenesis. Today, she and her team specialize in DNA structure-induced genetic instability. “We take our best, most educated guess to the bench, analyze our findings, then design the next move. It’s like solving a puzzle.”

Vasquez and her team recently found that a protein called HMGB1, previously thought to block DNA repair, actually enhances such repair.

An abundant chromosomal protein, HMGB1 has long been known to bind sites of damaged DNA, and recent evidence suggests that it is involved in pro-inflammatory processes. Several new drugs under development target the protein, in hopes of reducing the pathogenic inflammation that occurs in such conditions as rheumatoid arthritis and sepsis, or blood poisoning.

“However, therapy for arthritis is long-term,” she says, “and our findings suggest that depleting this protein could potentially leave patients more vulnerable to developing cancer.”

Vazquez knows that doing the work she love — solving the puzzles — in a lovely and peaceful setting is quite a perk.

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Renowned leader for Bioinformatics, Computational Biology

Scholar, investigator and inventor John Weinstein, M.D., Ph.D., joined MD Anderson in January 2008 as chair of the Department of Bioinformatics and Computational Biology, part of the Division of Quantitative Sciences, which plays a growing role in supporting the institution’s research institutes and extending its research mission. Among Weinstein’s accomplishments, he has invented a novel, patented method for measuring gene expression; developed the “Miner Suite” of widely used bioinformatic computer resources; and was cited as a pioneer of postgenomic biology, earning him a nomination for the National Medal of Technology in 2004. His 260 publications include 11 as first author in the journal Science. Bioinformatics and Computational Biology conducts collaborative research with clinical and basic science departments, and supports the need for quantitative sciences in the fields of genomics, proteomics, radiation therapy, molecular and cell biology, and computer-assisted diagnoses and image analysis.

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New Building Expands Research Opportunities

MD Anderson celebrated the 2008 groundbreaking for a 23,000-square-foot, $16 million building to accommodate growth of research programs and shared resource facilities at the Virginia Harris Cockrell Cancer Research Center campus near Smithville, Texas. Due to be completed by spring 2009, it will expand the Department of Cacinogenesis and the Center for Research on Environmental Health Sciences, funded by the National Institute of Environmental Health Sciences. Research programs on this campus are highly interactive and focused on cancer cause and prevention. Researchers are studying biochemical, cellular and molecular mechanisms of carcinogenesis, the process by which normal cells are transformed into cancer cells. New discoveries about the interplay between environmental factors and genetic factors in cancer development are emerging from these studies.

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New Partnerships Spur Drug Development

In an effort to bring the latest drugs to patients faster, MD Anderson has signed agreements with several pharmaceutical companies. “Strategic alliances are the way of the future where academe and industry work together toward common goals that benefit our patients,” says Robert Bast, M.D., vice president for translational research.

  • An agreement with AstraZeneca is helping advance understanding of neuropathic pain caused by cancer chemotherapy, a side effect that often limits optimal therapeutic dosing in cancer treatments. The alliance focuses on identifying neurobiological differences between cancer patients who develop chemotherapy-induced pain and patients who experience little or no pain.
  • An agreement with GlaxoSmithKline established a partnership to more effectively develop new therapeutic, diagnostic and imaging products of mutual interest. The alliance concentrates on integrated preclinical and clinical programs for disease intervention, addressing key questions in the lab and translating those findings to the clinic and then back to the lab. 

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P53 Presents a Different Face

New data show that restoring the function of the cell’s p53 gene, inactivated in many types of cancer, could just as easily express a mutant version of the protein, causing cancer cells to thrive and spread rather than die. Until this finding, reactivation of p53 was thought to have great therapeutic potential. While this may still be true, the gene is more complex than originally thought. “As we develop therapies to restore the function of p53, we need to make sure we first know what version of this gene is present in a patient’s tumor and then decide how to treat it,” says senior author Guillermina Lozano, Ph.D., chair of the Department of Genetics.

Reported in the May 2008 issue of the journal Genes and Development.

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'The Three Musketeers of Cancer' Ambush a Tumor Suppressor

New research illuminates a mechanism of attack by at least one of three cancer-causing proteins on FOXO3a, a member of a family of special tumor-suppressing proteins. “We know that FOXO3a is inactivated in about 80 percent of breast tumors, and that it’s likely to be inactivated in other solid tumors because each of these three major pathways that promote the formation and development of cancer target it. The implication is that activation of this protein (FOXO3a) would be a great therapeutic benefit because it would reintroduce a powerful tumor suppressor,” says Mien-Chie Hung, Ph.D., chair of the Department of Molecular and Cellular Oncology.

Reported in the Feb. 10, 2008, issue of Nature Cell Biology.

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Enzyme Active in Drug Resistance and Metastasis

Overexpression of an enzyme — tissue type transglutaminase (TG2) — in ovarian cancer is associated with increased tumor cell growth and adhesion, resistance to chemotherapy and lower overall survival rates. When researchers targeted and silenced TG2 in animal models, cancer progression was reversed, suggesting TG2 also may provide a novel therapeutic approach for late-stage ovarian cancer.

““TG2 appears to fuel different types of cancer through multiple molecular pathways, making it an important therapeutic target,” says Kapil Mehta, Ph.D., lead author and professor in the Department of Experimental Therapeutics.

His lab also has connected TG2 overexpression to drug-resistant and metastatic melanoma, breast cancer and pancreatic cancer.

Reported in the July 15, 2008, issue of Cancer Research.

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Pulmonary Aerosol Tackles Deadly Infections

An inhaled stimulant launches an immune system response in the lining fluids in the lung, which kills invading pathogens on contact — protecting mice against lethal pneumococcal pneumonia and other deadly bacterial, viral and fungal infections of the lungs. “We study airway inflammation, and we often think about that in a negative context, how to stop inflammation, as in the allergic inflammation that causes asthma. But surely the ability of airways to become inflamed is there for a good reason. So we asked: Can we set off a type of inflammation that strengthens protection against infection? The answer is, ‘Yes,’” says Burton Dickey, M.D.,senior author and chair of the Department of Pulmonary Medicine.

Reported at annual meeting of the American Society for Cell Biology in December 2007.

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Connecting Diet and Cancer Pathways

A restricted-calorie diet inhibited the development of precancerous growths in a skin cancer model, reducing the activation of two signaling pathways known to contribute to cancer growth and development. By contrast, an obesity-inducing diet activated those pathways, leading to cancer cell proliferation and survival. “These results, while tested in a mouse model for skin cancer, are broadly applicable to epithelial cancers (which comprise 80 percent of all cancers) in other tissues,” says John DiGiovanni, Ph.D., chair of the Department of Carcinogenesis and director of the Science Park-Research Division in Smithville, Texas.

Reported at the April 2008 annual meeting of the American Association for Cancer Research.

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Immunology – A Unique Combination Ignites Immune Response Usually Aimed at Fighting Infection

A simple, noninvasive way to detect bladder cancer may be to count copies of a specific gene, Aurora kinase A, in cells gathered from a urine sample. When the gene is overexpressed in urothelial cells, errors occur during cell division, creating either too few or too many chromosomes, instead of the normal pairs of 23.

“Abnormal chromosome counts are the most fundamental feature — the signature — of human cancers. As a biomarker, Aurora kinase A can enable early detection of bladder cancer in voided urine with high degrees of sensitivity and specificity,” says senior author Bogdan Czerniak, M.D., Ph.D., professor in the Department of Pathology.

Published in the Oct. 1, 2008, edition of the Journal of the National Cancer Institute.

Faculty Honors

Thomas W. Burke, M.D., executive vice president and physician-in-chief, was elected the 40th president of the Society of Gynecologic Oncologists.

Raymond N. DuBois, M.D., Ph.D., provost and executive vice president, became the fifth MD Anderson faculty leader to serve as president of the American Association for Cancer Research.

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© 2014 The University of Texas MD Anderson Cancer Center