Produced by the Office of Communications // June 23, 2011
New stem cell research could aid in battle against bulging waistlines
Innovative adult stem cell research by scientists at the Medical School could aid efforts to apply the brakes to stem cells that produce the type of fat ringing the waists of millions. Research appeared online ahead of the print issue of Cell Stem Cell.
The scientists have developed a bold approach for targeting fat-generating stem cells that one day could aid in the delivery of drugs that slow the cells' ability to direct fat expansion. Because these cells also are used in regenerative medicine, this approach may have wide applications. The cells are termed adipose stem cells.
The researchers used small artificial proteins (peptides) in a mouse model to identify a marker on the surface of adipose stem cells. Markers are molecules specifically expressed on individual cell types. The scientists screened about 100 billion peptides before finding one that was specific for mouse and human adipose stem cells.
“This marker, called delta-decorin, is specifically expressed on the surface of adipose stem cells, which are responsible for the production of white adipose tissue,” said Dr. Mikhail Kolonin, the study’s senior author and assistant professor of molecular medicine. “This is the first prospective marker to be discovered for this particular type of adult stem cell.”
Dr. Alexes Daquinag, the study’s first author and postdoctoral fellow, said, “In obesity, you have an overgrowth of white adipose tissue. It is made of adipocytes (fat cells), and one way to stop obesity is to target the progenitor cells—adipose stem cells.”
Kolonin added, “The existing approaches to identify adipose stem cells are based on combinations of semi-specific markers and are unreliable. Now we are able to target these cells with a new peptide probe for the purpose of tracing them in the body or controlled elimination.”
The researchers report that delta-decorin, a modification of a previously defined protein, interacts with another clinically important protein called resistin on the surface of adipose stem cells. “The decorin-resistin connection is particularly interesting because both decorin and resistin have been previously implicated in Type-2 diabetes and other inflammation-related disease,” Kolonin said.
“The next step will involve preclinical tests to see if we can develop the identified peptide into compounds that target these adipose stem cells,” Kolonin said. “By depleting the adipose tissue progenitors, we may be able to provide long-term control of white fat.”
Kolonin said he believes this approach could complement an anti-obesity compound he developed at The University of Texas MD Anderson Cancer Center before joining the UTHealth faculty. The compound called “Adipotide” works by targeting the blood vessels in fat and is licensed to Ablaris Therapeutics, Inc.
“Helping people lose weight might also reduce their risk of cardiovascular diseases, certain types of cancer, Type 2 diabetes, and other obesity-related diseases,” Kolonin said. Previous studies in Kolonin’s laboratory have demonstrated the role of adipose stem cells in cancer progression.
Other collaborators from the Medical School include Dr. Paul Simmons, C. Harold and Lorine G. Wallace Distinguished University Chair and director of the Centre for Stem Cell Research; Dr. Yan Zhang, research scientist; and Felipe Amaya-Manzanares, research associate.
The study is titled “An Isoform of Decorin is a Resistin Receptor on the Surface of Adipose Progenitor Cells.” The work was supported by Komen for the Cure, the American Heart Association, and the Cancer Prevention & Research Institute of Texas.
Kolonin’s laboratory is in the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. He is also on the faculty of the Graduate School of Biomedical Sciences at Houston and is a John S. Dunn Research Scholar.
— Robert Cahill, Office of Advancement, Media Relations
Researchers link chromosome region
to thoracic aortic disease
Patients with thoracic aortic aneurysms that lead to acute aortic dissections are 12 times more likely to have duplications in the DNA in a region of chromosome 16 (16p13.1) than those without the disease, according to a study led by genetic researchers at the Medical School.
The results of the innovative study, which included researchers at Baylor College of Medicine, are published in the June 16 issue of the open-access journal PLoS Genetics.
In human DNA, there are regions of the DNA that are deleted or duplicated, and these are referred to as copy number variants, or CNVs. These CNVs can cause a loss of the number of copies of a gene from two to one (deletion), or cause more copies of a gene from two to three (duplications). Researchers are just beginning to identify a subset of these CNVs that can increase a person’s risk of getting a particular disorder.
“We're just starting to understand copy number variants and their link to disease,” said Dr. Dianna Milewicz, senior author, holder of the President George H.W. Bush Chair in Cardiovascular Research, and director of the Division of Medical Genetics. “This is the first recurrent CNV discovered to be associated with thoracic aortic aneurysms and dissections. In addition, it is the first recurrent copy number variant to cause a predisposition to more than one disorder, neuropsychiatric conditions and thoracic aortic disease.”
This region of chromosome 16 (16p13.1) contains nine genes, and the additional copy of any of these nine genes can potentially cause predisposition to different problems. Duplications of 16p13.1, which are present in approximately one in 1,000 people, have been associated with a variety of neuropsychiatric disorders, such as schizophrenia and attention-deficit hyperactivity disorder (ADHD).
Those nine genes include MYH11, whose dysfunction is known to affect the smooth muscle cell tissue in major arteries in the body, including the thoracic aorta. A weakness in the lining of the thoracic aorta, which carries blood from the heart to the rest of the body, can lead to an aneurysm and/or dissection, which can cause sudden death. An estimated 8,000 people die annually from thoracic aortic aneurysms and dissections.
Researchers found 16p13.1 duplications in eight of 765 patients with non-familial, non-syndrome-related thoracic aortic aneurysms and dissections compared to four patients in 4,569 controls. The 12-fold increased risk for aortic disease associated with this duplication of this region of chromosome 16 is greater than the three-fold increase for schizophrenia and the five-fold increase for ADHD.
“The results of this study could affect clinical care because it appears patients with 16p13.1 duplications have an aggressive form of the thoracic aortic disease that causes aneurysms to dissect at smaller diameters,” Milewicz said. “Also, once doctors are able to use the entire genome, people with duplications in 16p13.1 would need to have their aortas monitored.”
Some of the patient samples used for this study were obtained from GenTAC, a National Institutes of Health (NIH)-funded registry of patients with thoracic aortic disease.
UTHealth co-authors of the article, “Recurrent Chromosome 16p13.1 Duplications are a Risk Factor of Aortic Dissections,” include Dr. Shao-Qing Kuang, assistant professor of internal medicine; Dr. Dong-chaun Guo, assistant professor of internal medicine; Dr. Siddharth Prakash, assistant professor of internal medicine; Callie Kwartler, research assistant, Graduate School of Biomedical Sciences; Ellen Regalado, genetic counselor; Dr. Jiumei Cao, post-doctoral fellow; Dr. Ralph Johnson, assistant professor of internal medicine; Dr. Hazim Safi, professor and chair of the Department of Cardiothoracic and Vascular Surgery; and Dr. Anthony Estrera, associate professor of cardiothoracic and vascular surgery.
Other co-authors include Dr. John Belmont, Dr. Scott LeMaire, and Dr. Joseph Coselli, all of Baylor College of Medicine.
Other collaborative authors are from the Department of Molecular and Human Genetics and Division of Cardiothoracic Surgery, Baylor College of Medicine; and GenTAC participating centers including Johns Hopkins University, Weill Medical College of Cornell University, and the National Heart, Lung and Blood Institute.
Funding for the study came from the NIH, the Vivian L. Smith Foundation, the Tex-Gen Foundation, and the Doris Duke Charitable Trust Grant.
— Deborah Mann Lake, Office of Advancement, Media Relations
Scleroderma study identifies roadblocks
Systemic scleroderma has slowed Tracy Zinn, but it has not stopped her from her working. Thanks in part to determination and an accommodating employer, Zinn is now in her 13th year as an account executive for a firm that produces educational software. But, many with the incapacitating disease are not as fortunate.
In the United States, the work disability rate for people with systemic scleroderma, also known as systemic sclerosis, is two to three times that of people with some other rheumatic conditions, according to research data from Medical School investigators.
Systemic scleroderma is a chronic autoimmune disease affecting about 100,000 people in the United States. It is associated with hardening of the skin and also can lead to thickening of blood vessels, lungs, and other organs. Depending on which organ is affected, the disease can be fatal.
To help people with systemic scleroderma obtain or retain jobs, researchers investigated determinants of work disability in one of the largest longitudinal cohorts of systemic scleroderma patients in the country—the Genetics versus Environment in Scleroderma Outcome Study (GENISOS).
Researchers found that demographic, clinical, and psychosocial factors contribute to systemic scleroderma-related work disability. Findings are online and are scheduled to appear in the August print issue of Seminars in Arthritis and Rheumatism.
Lower educational level, more severe fatigue, and lung involvement (thickening in the lung tissue and vessels), as well as less social support, were associated with work disability in the early stages of the disease. In patients who were working when they entered the GENISOS study, non-Caucasians in addition to those with more severe fatigue and lung involvement were at higher risk of developing a work disability due to their health.
The silver lining of the study is that progress is being made in addressing at least one of the medical factors, and actions can be taken to address two of the non-medical factors in some circumstances.
“Severity of lung involvement is the most prominent clinical factor that predicts work disability among patients with scleroderma,” said Dr. Shervin Assassi, the study’s senior author and assistant professor of medicine. “We are presently investigating clinical, genetic, and other biological markers that can predict the course of scleroderma lung disease.”
Dr. Maureen Mayes, a study co-author, professor and Elizabeth Bidgood Chair in Rheumatology, said the study suggests that retraining may be an option for people no longer able to perform their current duties.
Further, additional support may help people keep or get a job, said Dr. Roozbeh Sharif, lead author and a postdoctoral fellow. “Patients who had a better interpersonal support system from their family members and friends had a lower chance of developing work disability,” he said. “These findings further emphasize the important impact of psychosocial factors on the scleroderma patient and underscore the beneficial role of strong social support from family, friends, and patient support groups.”
The work disability study was based on an analysis of 284 people in the GENISOS cohort. About 44 percent had a work disability when they enrolled. After approximately 4.5 years of follow-up, the work disability rate rose to 62 percent. The ongoing study is conducted at UTHealth, The University of Texas Health Science Center San Antonio, and The University of Texas Medical Branch at Galveston.
Medical School contributors include: Dr. John Reveille, professor, George S. Bruce, Jr. Professorship in Arthritis and Other Rheumatic Diseases and Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders; Dr. Rosa Estrada-Y-Martin, associate professor of medicine; Dr. Frank Arnett, former professor of medicine; and Deepthi Nair, scientific programmer. Alison Brown is the coordinator of GENISOS at UTHealth.
Other collaborators include: Dr. Perry Nicassio, University of California, Los Angeles; Dr. Emilio Gonzalez and Dr. Terry McNearney, both at UTMB; and Dr. Hilda Draeger, UT Health Science Center San Antonio.
The study titled “Determinants of Work Disability in Patients with Systemic Sclerosis: A Longitudinal Study of the GENISOS Cohort” received support from the National Institutes of Health Center of Research Translation, University Clinic Research Center, the Center for Clinical and Translational Sciences, and the National Center for Research Resources.
— Robert Cahill, Office of Advancement, Media Relations
Entering first-year student wins TMA minority scholarship
The Texas Medical Association (TMA) presented Natalie Diaz, of Carrollton, one of nine $5,000 scholarships for minority students entering Texas medical schools. Diaz will enter the Medical School as a first-year student this fall.
Diaz was chosen from a highly competitive field of promising future physicians entering medical school this fall due to her high academic achievement, commitment to community service, and outstanding health care experience.
She graduated from Texas Christian University and wants to care for patients in rural Texas as a pediatrician or family physician and foster a caring patient-doctor relationship, especially with Spanish-speaking patients.
TMA awarded the scholarships during its annual TexMed conference in Houston. TMA created the Minority Scholarship Program to help diversify the physician workforce to fulfill the needs of Texas' increasingly diverse population. The scholarship encourages exceptional minority students to enter medicine by lightening the financial burden of medical school. Since the program's inception, TMA has awarded 65 scholarships totaling $325,000 to minority medical students.
This year’s nine scholarships were made possible by a grant from the association's philanthropic arm, the TMA Foundation, thanks to generous gifts from physicians, their families, and corporate supporters. Diaz’s scholarship is provided by a gift from H-E-B.
Located in Austin, TMA is the largest state medical society in the nation, representing more than 45,000 physician and medical student members.
Events to know
Blood Drive at UT Physicians at Sienna Village.
9:30 a.m.–12:30 p.m., 8810 Hwy. 6, Suite 100, Missouri City.
Research Coordinator Forum: Cynthia Edmonds, director, Office of Research Support Committees, and Vicky Woodruff, research coordinator, Neurosurgery, will talk about “Humanitarian Use Devices,” medical devices intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in fewer than 4,000 individuals in the United States per year.
11:30 a.m.–1 p.m., MSB 2.135.
Lunch will be available for the first 50 attendees.
Department of Integrative Biology and Pharmacology Seminar Series: Dr. Melanie Cobb (UT Southwestern) presents, “Nutrient sensing, insulin synthesis and neuroendocrine cancer: contour lines on the same MAPK.”
2–3 p.m., MSB 2.135.
Family & Community Medicine Grand Rounds: Dr. Andrew DuPont, assistant professor of internal medicine, presents, “Approach to Diarrhea.”
1–2 p.m., MSB 2.135.
Digital Storytelling in Medical Education: Hands-on session to learn digital storytelling methodology and an easy-to-use software to create digital stories.
Noon–1 p.m., MSB B.140.
Register here. Walk-ins also welcome! Direct questions to Anne Rudnicki, Ed.D., 713.500.5909.
Independence Day holiday
Neurosurgery Grand Rounds: Dr. Baruch Brody, (Baylor College of Medicine) presents, “Ethical Issues in the Conduct of Surgical Trials and in the Diffusion of Surgical Innovations.”
8–9 a.m., MSB G.100.
CME/CNE Credit provided.
Drs. Johnnie Frazier, Julia Shelburne, Mark Hormann, and Allison Ownby recently presented “An Inpatient Hospital Team Based Learning Curriculum” at the AAMC Southern Group of Educational Affairs meeting.
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