HOUSTON -- (September 30, 2008) -- Twelve Baylor College of Medicine researchers have been awarded funding through the U.S. Department of Health and Human Services along with researchers from six additional Texas institutions, Senator Kay Bailey Hutchison (R-TX) announced.

"This funding will help Texas health institutions expand their knowledge and understanding of science and medicine," said Hutchison.

"The research represented by these grants covers many important fields of study at Baylor College of Medicine," said Dr. Peter G. Traber, president and CEO at BCM. "We appreciate Senator Hutchison's leadership in support of biomedical science."

Researchers at BCM receiving funding include:

• Dr. Jue (Jade) D. Wang, assistant professor of molecular and human genetics, received $2,302,500 for her project, The Molecular Interface of Replication Elongation and the Cellular Environment from the Office of the Director at the National Institutes of Health. Wang also received the 2008 National Institutes of Health Director's New Innovator Awards, a program to support young scientists early in their careers, earlier this year.
• Dr. Aleksandar Milosavljevic, associate professor of molecular and human genetics, received $1,364,573 for his project, Epigenomics Data Analysis and Coordination Center at BCM from the National Institute on Drug Abuse.
• Dr. Olivier Lichtarge, professor of molecular and human genetics, received $423,459 for his project, Functional Determinants in G Protein-Coupled Receptors from the National Institute of General Medical Sciences.
• Dr. H. Daniel Lacorazza, assistant professor of pathology and immunology, received $383,750 for his project, Transcriptional Regulation of Development and Maintenance of Memory T Lymphocytes from the National Institute of Allergy and Infectious Diseases.
• Dr. Jenny Chang, associate professor of medicine and medical director of the Lester and Sue Smith Breast Center at BCM, received $475,325 for her project, Targeting Notch, PI3K-AKT and other novel pathways in breast cancer stem cells from the National Cancer Institute.
• Dr. David Corry, associate professor of medicine-immunology, received $697,014 for his project, Molecular Phenotypes for Lung Diseases from the National Heart, Lung, and Blood Institute.
• Dr. Karen Cullen, associate professor of pediatrics-nutrition, received $360,449 for her project, Family Eats: Cancer Prevention for Families from the National Cancer Institute.
• Dr. Graeme Mardon, professor of pathology, received $274,764 for his project, Molecular Genetics Emphasizing Vision Research from the National Eye Institute.
• Dr. Mary Mariscalco, associate professor of pediatrics-critical care, received $183,632 for her project, Research Training in Pediatric Critical Care Medicine from the National Heart, Lung, and Blood Institute.
• Dr. Hardeep Singh, assistant professor of medicine-health services research, received $421,506 for his project, Using Electronic Data to Improve Care of Patients with Known or Suspected Cancer from the Agency for Healthcare Research and Quality.
• Dr. Susan Marriott, professor of molecular virology and microbiology, received $223,295 for her project, Transforming Potential of Emerging Human Retroviruses from the National Institute of Allergy and Infectious Diseases.
• Dr. Virginia Moyer, professor of pediatrics, received $299,764 for her project, Safe Passages: A Toolkit to Ensure Quality Transitions from NICU to Ambulatory Care from the Agency for Healthcare Research and Quality.

HOUSTON -- (September 30, 2008) -- Three injections of anthrax vaccine given into the muscle stimulate comparable antibody responses and cause fewer adverse reactions than four doses given under the skin, said a consortium of researchers that included those from Baylor College of Medicine in a report in the current Journal of the American Medical Association.

"We expect that reducing the number of adverse reactions will lead to a higher level of acceptability of the vaccine," said Dr. Wendy Keitel, professor of molecular virology and microbiology at BCM and director of the Vaccine Treatment and Evaluation Unit at BCM. "And reducing the number of times the vaccine is given will reduce the cost and complexity of delivering the entire program."

Eliminating second dose

Anthrax vaccine is primarily given to people who are at risk for repeated exposure to anthrax spores, such as military personnel deployed to areas where they face an increased risk of infection with the bacteria and people who work with the organism in the laboratory. Eliminating the second dose of the currently recommended schedule would make it easier to fully vaccinate someone, said Keitel.

Researchers studied the ability of a reduced dose schedule to stimulate immune responses and reactions at the vaccine injection site in 1,005 healthy adults between the ages of 18 and 61 years who had not previously received the anthrax vaccine. Study participants were placed at random into one of six groups. Some groups received four scheduled doses at weeks 0, two and four weeks and six months; some groups received placebo as the second dose at two weeks; and some received only placebo injections.

Muscle vs. under the skin

Researchers evaluated antibody responses to the vaccine in the study participants seven months after they received the first dose and found that giving fewer injections into the muscle was comparable to the usual schedule of four given under the skin. They also noted fewer and milder side effects in those who received injections into the muscle rather than under the skin.

Other BCM researchers contributing to the study are Dr. Hanaa El Sahly, assistant professor of molecular virology and microbiology, Nanette Bond, P.A.C., study coordinator, and staff from the Vaccine Research Center. Contributing institutions include University of Alabama at Birmingham, Walter Reed Army Institute for Research, Mayo Clinic, and Emory University School of Medicine.

The study was funded and sponsored by the Centers for Disease Control and Prevention. The CDC was responsible for the development, study protocol and for statistical analyses.

The study can be found at www.jama.ama-assn.org/.

HOUSTON -- (September 26, 2008) -- Three enzymes called phosphatases that shut down a molecule called SRC-3 (steroid receptor coactivator 3) could provide a new pathway for fighting cancer, particularly tumors of the breast and prostate, said researchers at Baylor College of Medicine in a report that appears in the current issue of the journal Molecular Cell.

"This kind of information provides a target for the production of drugs against cancer," said Dr. Bert O'Malley, chair of molecular and cellular biology at BCM. "One can already find drugs that stimulate or inhibit phosphatases in other disease processes."

O'Malley and his colleagues had already determined that SRC-3 is an oncogene or cancer-promoting gene as well as a master switch in the cell. Phosphorylation or adding a phosphate molecule activates its cancer-promoting activities. In this study, the researchers identified three phosphatases that promote removal of the phosphate and thus halt the activity of SRC-3.

Of the three identified, PDXP, PP1, and PP2A, PP1 not only stops SRC-3 activity, it also stops the degradation of the co-activator. SRC-3 then builds up in cells, but without the phosphate, it is a dead molecule that does not function and may even further inhibit tumor growth.

Providing new avenues for fighting cancer is an important outcome of basic science, said O'Malley, who is also associate director for basic research in The Dan L. Duncan Cancer Center at BCM. "In cancer right now, many drugs work the same way. They are toxic to all cells. Because the cancer cell grows faster, the drug is more toxic, but there is nothing selective about the process. In the past decade, we have realized that there has to be a better, more intellectual approach to cancer. In fact, some already exist."

For example, the drug Herceptin targets breast cancer cells that carry the protein Her2/neu. Finding drugs that stop the activation of SRC-3, found at high levels in some breast tumors, could provide another avenue of treatment that could target just the cancer cells.

One study, published by Dr. C. Kent Osborne, director of the Lester and Sue Smith Breast Center at BCM, showed that women whose tumors have both the Her2/neu protein and high levels of SRC-3 are less likely to be helped by drugs such as tamoxifen and more likely to die quickly of their disease. Finding a way to stop Her2/neu and shut down SRC-3 could make the tumor cell's growth controllable, O'Malley said.

Others who took part in this work include Chao Li, Yao-Yun Liang, Xin-Hua Feng, Sophia Y. Tsia and Ming-Jer Tsai, all of BCM.

Funding for this study came from the National Institutes of Health and the Welch Foundation.

This report can be found at www.molecule.org.

For more information on basic research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.

HOUSTON -- (September 26, 2008) -- Baylor College of Medicine has named Laura Elena Muñoz Arnold, president of the Arnold Family Foundation, to its board of trustees.

The board announced the appointment Wednesday.

"Laura Arnold's business, legal and community service experience, along with her dedication to education initiatives, will be of great benefit to the college's leadership in planning our strategic missions," said Dr. Peter G. Traber, BCM president and CEO. "We are thrilled to have her as a trustee of the college."

A magna cum laude graduate of Harvard College and a graduate of Yale Law School, Arnold also has a master's of philosophy in European Studies from the University of Cambridge.

The Arnold Family Foundation, founded in 2004, supports education initiatives and social and human services programs.

Arnold also serves on the Houston regional board of Teach for America. She was a co-founder, executive vice president and general counsel at Houston-based Cobalt Energy International, a private equity exploration and production company. She joined Cobalt after working in the New York law firm of Wachtell, Lipton, Rosen & Katz, where she was a corporate attorney specializing in mergers and acquisitions.

Following graduation from the University of Cambridge, she was a professor of international relations in Mexico at the Centro de Estudios Profesionales de Chiapas "Fray Bartolomé de las Casas" and at the Instituto Tecnológico y de Estudios Superiores de Monterrey in Tuxtla Gutiérrez, Chiapas. During the 2000-2001 term, she clerked for the Honorable Judith W. Rogers of the U.S. Court of Appeals for the District of Columbia Circuit.

HOUSTON -- (September 25, 2008) -- A link between certain behaviors and the lack of the protein associated with Rett Syndrome – a devastating autism spectrum disorder – demonstrates the importance of MeCP2 (the protein) and reveals never-before recognized functions associated with aggression and obesity, said researchers at Baylor College of Medicine in a report in the current issue of the journal Neuron.

"This protein is critical for the proper function of majority of neurons," said Dr. Huda Y. Zoghbi, a BCM professor of pediatrics, neurology, neuroscience, molecular and human genetics and a Howard Hughes Medical Institute investigator who is senior author on the paper. Zoghbi and her laboratory discovered the Rett gene.

Rett Syndrome affects between 1 in 10,000 females who express a wide variety of symptoms, most of them neurological.

"Observe a girl with Rett Syndrome and you will see that she has most of the neurological symptoms you are familiar with," Zoghbi said. "There are movement problems, balance problems, tremor, seizures, autism, learning and memory problems, anxiety and even more."

Girls with Rett Syndrome lack MeCP2 (found on the X chromosome) in as many as 50 percent of their neurons. The severity and breadth of symptoms they experience depend on the percentage of neurons that lack the protein.

To determine which neurons affects which behaviors, Zoghbi and her colleagues engineered mice to lack MeCP2 in small populations of neurons in the hypothalamus, a command center of the brain that controls several physiological states.

When they eliminated the MeCP2 protein from one specific group of neurons in the hypothalamus, the animals showed one feature of Rett syndrome: increased levels of a stress hormone in response to stress. The animals also became aggressive when they were put into a novel situation.

"That meant that the few neurons that lacked MeCP2 govern this behavior," she said. "It also suggested that we need this protein to temper the response of our neurons so we behave appropriately when we experience a new social setting."

People with autism frequently get frustrated in novel situations, she said. A colleague in Germany reported seeing aggression in patients with milder Rett Syndrome.

"The other thing that surprised us was that the animals gained weight and kept on getting more obese as they got older," she said. "They ate unstoppably. In the absence of MeCP2, the signals that work within the hypothalamus to tell us we are full and need to stop eating are in part regulated by this protein. Without MeCP2, the neurons don't get the signal and you keep eating. It reveals a function of the protein not suspected before," she said.

The study also demonstrates that this technique – knocking out essential proteins in small populations of cells in the brain – could help reveal which neurons are important for which behaviors.

In the future, Zoghbi and her colleagues plan to study the function of MeCP2 in other neurons using the same technique.

Others who took part in the research include Sharyl L. Fyffe, Jeff. L. Neul, Rodney C. Samaco, Hsiao-Tuan Chao, Shay Ben-Shachar, Paolo Moretti, and Bryan E. McGill, all of BCM and Evan H. Goulding, Elinor Sullivan and Laurence H. Tecott, all of the University of California San Francisco.

Funding for this work came from the National Institutes of Health/National Institute of Neurological Disorders & Stroke, National Institute of Child Health & Human Development Mental Retardation & Developmental Disabilities Research Center, International Rett Syndrome Foundation, Autism Speaks, Simons Foundation.

The full article can be found at www.neuron.org.

For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.