Hamon Center for Regenerative Science and Medicine

Dallas, TX, United States

Hamon Center for Regenerative Science and Medicine

Dallas, TX, United States
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News Article | May 8, 2017
Site: www.rdmag.com

UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray – findings that could one day help identify possible treatments for balding and hair graying. “Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair,” said Dr. Lu Le, Associate Professor of Dermatology with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.” The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation. When they deleted the SCF gene in the hair progenitor cells in mouse models, the animal’s hair turned white. When they deleted the KROX20-producing cells, no hair grew and the mice became bald, according to the study. Dr. Le, who holds the Thomas L. Shields, M.D. Professorship in Dermatology, said he and his researchers serendipitously uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves. Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Dr. Le, a member of the Hamon Center for Regenerative Science and Medicine. What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF – or that cells involved in hair shaft creation make the KROX20 protein, he said. If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs. But without SCF, the hair in mouse models was gray, and then turned white with age, according to the study. Without KROX20-producing cells, no hair grew, the study said. UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people – as well as in male pattern baldness, Dr. Le said. The research also could provide answers about why we age in general as hair graying and hair loss are among the first signs of aging. Other researchers include first author Dr. Chung-Ping Liao, Assistant Instructor; Dr. Sean Morrison, Professor and Director of the Children’s Medical Center Research Institute at UT Southwestern and of Pediatrics, and Howard Hughes Medical Institute Investigator, who holds the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children’s Research Institute at UT Southwestern and the Mary McDermott Cook Chair in Pediatric Genetics; and Reid Booker, a former UT Southwestern researcher. The research was supported by the National Cancer Institute, Specialized Programs of Research Excellence (SPORE) grant, National Institutes of Health, the Dermatology Foundation, the Children’s Tumor Foundation, and the Burroughs Wellcome Fund.


News Article | May 8, 2017
Site: www.chromatographytechniques.com

UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray – findings that could one day help identify possible treatments for balding and hair graying. “Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair,” said Lu Le, associate professor of dermatology with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.” The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation. When they deleted the SCF gene in the hair progenitor cells in mouse models, the animal’s hair turned white. When they deleted the KROX20-producing cells, no hair grew and the mice became bald, according to the study. Le, who holds the Thomas L. Shields, M.D. Professorship in Dermatology, said he and his researchers serendipitously uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves. Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Le, a member of the Hamon Center for Regenerative Science and Medicine. What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF – or that cells involved in hair shaft creation make the KROX20 protein, he said. If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs. But without SCF, the hair in mouse models was gray, and then turned white with age, according to the study. Without KROX20-producing cells, no hair grew, the study said. UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people – as well as in male pattern baldness, Le said. The research also could provide answers about why we age in general as hair graying and hair loss are among the first signs of aging.


News Article | May 8, 2017
Site: www.chromatographytechniques.com

UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray – findings that could one day help identify possible treatments for balding and hair graying. “Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair,” said Lu Le, associate professor of dermatology with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.” The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation. When they deleted the SCF gene in the hair progenitor cells in mouse models, the animal’s hair turned white. When they deleted the KROX20-producing cells, no hair grew and the mice became bald, according to the study. Le, who holds the Thomas L. Shields, M.D. Professorship in Dermatology, said he and his researchers serendipitously uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves. Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Le, a member of the Hamon Center for Regenerative Science and Medicine. What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF – or that cells involved in hair shaft creation make the KROX20 protein, he said. If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs. But without SCF, the hair in mouse models was gray, and then turned white with age, according to the study. Without KROX20-producing cells, no hair grew, the study said. UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people – as well as in male pattern baldness, Le said. The research also could provide answers about why we age in general as hair graying and hair loss are among the first signs of aging.


News Article | May 8, 2017
Site: www.eurekalert.org

May 5, 2017 - UT Southwestern Medical Center researchers have identified the cells that directly give rise to hair as well as the mechanism that causes hair to turn gray - findings that could one day help identify possible treatments for balding and hair graying. "Although this project was started in an effort to understand how certain kinds of tumors form, we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair," said Dr. Lu Le, Associate Professor of Dermatology with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. "With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems." The researchers found that a protein called KROX20, more commonly associated with nerve development, in this case turns on in skin cells that become the hair shaft. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF) that the researchers showed is essential for hair pigmentation. When they deleted the SCF gene in the hair progenitor cells in mouse models, the animal's hair turned white. When they deleted the KROX20-producing cells, no hair grew and the mice became bald, according to the study. The findings are published online in Genes & Development. Dr. Le, who holds the Thomas L. Shields, M.D. Professorship in Dermatology, said he and his researchers serendipitously uncovered this explanation for balding and hair graying while studying a disorder called Neurofibromatosis Type 1, a rare genetic disease that causes tumors to grow on nerves. Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Dr. Le, a member of the Hamon Center for Regenerative Science and Medicine. What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF - or that cells involved in hair shaft creation make the KROX20 protein, he said. If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs. But without SCF, the hair in mouse models was gray, and then turned white with age, according to the study. Without KROX20-producing cells, no hair grew, the study said. UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people - as well as in male pattern baldness, Dr. Le said. The research also could provide answers about why we age in general as hair graying and hair loss are among the first signs of aging. Other researchers include first author Dr. Chung-Ping Liao, Assistant Instructor; Dr. Sean Morrison, Professor and Director of the Children's Medical Center Research Institute at UT Southwestern and of Pediatrics, and Howard Hughes Medical Institute Investigator, who holds the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children's Research Institute at UT Southwestern and the Mary McDermott Cook Chair in Pediatric Genetics; and Reid Booker, a former UT Southwestern researcher. The research was supported by the National Cancer Institute, Specialized Programs of Research Excellence (SPORE) grant, National Institutes of Health, the Dermatology Foundation, the Children's Tumor Foundation, and the Burroughs Wellcome Fund. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.


News Article | October 31, 2016
Site: www.eurekalert.org

DALLAS - October 31, 2016 - Normal, healthy heart muscle is well-supplied with oxygen-rich blood. But UT Southwestern Medical Center cardiologists have been able to regenerate heart muscle by placing mice in an extremely low-oxygen environment. Researchers with the Hamon Center for Regenerative Science and Medicine gradually lowered the oxygen in the air breathed by mice until it was at 7 percent - about the concentration of oxygen at the top of Mt. Everest. After two weeks in the low-oxygen environment, the heart muscle cells - called cardiomyocytes - were dividing and growing. Under normal circumstances cardiomyocytes do not divide in adult mammals. The findings, published in Nature, build upon years of work that began with the discovery that the hearts of newborn mammals have the ability to regenerate, similar to the way skin has the ability to repair itself after a cut. But this ability of heart muscle to regenerate is quickly lost in the following weeks as the animal ages and cardiomyocytes are bathed in the oxygen-rich environment of the beating heart, causing damage to the cells. "The adult human heart is not capable of any meaningful repair following a heart attack, which is why heart attacks have such a devastating impact," said Dr. Hesham Sadek, Associate Professor of Internal Medicine and with the Hamon Center. "Though counterintuitive, we've shown that severely lowering oxygen exposure can sidestep damage to cells caused by oxygen and turn cell division back on, leading to heart regrowth." In the current study, researchers lowered the oxygen level from the normal 21 percent to 7 percent over a period of weeks, then monitored the mass and function of the heart. They demonstrated that reduction in oxygen leads to both an increase in cardiomyocytes and improved heart function. The researchers had tried a 10 percent oxygen environment, but there was no heart regrowth in the 10 percent oxygen environment. To avoid oxygen damage to cells, oxygen levels needed to be very low, a situation referred to as hypoxia. "This work shows that hypoxia equivalent to the summit of Mt. Everest can actually reverse heart disease, and that is extraordinary," said Dr. Benjamin Levine, Professor of Internal Medicine who holds the Distinguished Professorship in Exercise Sciences, and who directs the Institute of Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas, a joint program of UT Southwestern and Texas Health Resources. "In theory, creating a low-oxygen environment could lead to repair not only of heart muscle, but of other organs as well," said Dr. Sadek, who holds the J. Fred Schoellkopf, Jr. Chair in Cardiology. "Although exposure to this level of hypoxia can result in complications, it is tolerated in humans when performed in a controlled setting." The latest findings build upon previous research by UT Southwestern scientists that includes: This work was supported by the National Institutes of Health, in addition to support from the Hamon Center for Regenerative Science and Medicine, whose goal is to understand the basic mechanisms for tissue and organ formation, and then to use that knowledge to regenerate, repair and replace tissues damaged by aging and injury. UT Southwestern established the Hamon Center for Regenerative Science and Medicine in 2014 with a $10 million endowment gift from the Hamon Charitable Foundation to further research into the relatively new field of regenerative medicine. Other UT Southwestern researchers who contributed to the study are Dr. Yuji Nakada, Assistant Instructor of Internal Medicine; Dr. Diana Canseco, Instructor of Internal Medicine; SuWanee Thet, Research Associate; Dr. Salim Abdisalaam, postdoctoral researcher; and Dr. Wataru Kimura, Visiting Assistant Professor of Internal Medicine. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year.


News Article | October 26, 2016
Site: www.eurekalert.org

DALLAS - Oct.26, 2016 - Researchers at UT Southwestern Medical Center's Hamon Center for Regenerative Science and Medicine have identified a pathway essential to heart formation and, in the process, unveiled a mechanism that may explain how some previously puzzling segments of the genome work. The DNA sequence they studied - which they named Upperhand (Uph) - is located just before a gene called Hand2, which controls the development of the heart as it grows in the womb. "These findings uncover a new and unexpected step in the control of heart formation whereby one gene, Upperhand, regulates the expression of the neighboring gene, Hand2, by an unusual mechanism," said Dr. Eric Olson, Director of the Hamon Center for Regenerative Science and Medicine, and Chairman of Molecular Biology. Upperhand works something like a safe, which holds the controls for Hand2 locked inside it. Upperhand has to be opened up first for the Hand2 controls to be exposed. That ultimately allows Hand2 to set in motion a whole sequence of events that are crucial to formation of the heart. Upperhand also may help explain the mystery behind why some DNA sequences don't serve as templates for synthesizing proteins like other DNA sequences. Those that don't are called non-coding DNA and scientists have been pondering what they do and how they work. "These non-coding sequences are the mysterious "dark matter" of the genome," said Dr. Olson, who holds the Robert A. Welch Distinguished Chair in Science, the Pogue Distinguished Chair in Research on Cardiac Birth Defects, and the Annie and Willie Nelson Professorship in Stem Cell Research. Upperhand is one such "non-coding" DNA that doesn't serve as the template for a protein. "Why would it be located before Hand2, we wondered? What we learned is that the [controls] for Hand2 just happen to be trapped inside Upperhand," Dr. Olson said. "This is probably a general mechanism for the control of many genes that are important in development, because so many cardiac control genes are adjacent to non-coding RNAs and nobody ever understood why that is." The research, which appears online in Nature, was supported by grants from the National Institutes of Health, Foundation Leducq Networks of Excellence, Cancer Prevention and Research Institute of Texas, and the Robert A. Welch Foundation, as well as a pre-doctoral fellowship from the American Heart Association and a Muscular Dystrophy Association Development Grant. Other UT Southwestern scientists who contributed to this research are Dr. Kelly M. Anderson, former graduate student; Dr. Douglas M. Anderson, former postdoctoral fellow; John McAnally, research scientist in Medicine; and Dr. Rhonda Bassel-Duby, Associate Director of the Hamon Center for Regenerative Science and Medicine and Professor of Molecular Biology. UT Southwestern's Hamon Center for Regenerative Science and Medicine was made possible by a $10 million endowment gift from the Hamon Charitable Foundation, and was generously supported by the State of Texas in the 84th Legislative Session. The Center's goal is to understand the basic mechanisms for tissue and organ formation, and then to use that knowledge to regenerate, repair, and replace tissues damaged by aging and injury. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year. This news release is available on our website at http://www.utsouthwestern.edu/news. To automatically receive news releases from UT Southwestern via email, subscribe at http://www.


News Article | February 4, 2017
Site: www.techtimes.com

Researchers have discovered that a developmental anticancer agent has the ability to support regeneration in damaged heart tissues, opening up a possible new treatment option for heart disease. In a study published in the journal Proceedings of the National Academy of Sciences, Lawrence Lum and colleagues detailed their discovery, outlining their work on a cancer drug targeting Wnt signaling molecules. These molecules are necessary for regenerating tissues but also have a role in cancer development, and essential to Wnt protein production in people is the porcupine (Porcn) enzyme. It was while they were trying to inhibit the Porcn enzyme that the researchers discovered their cancer drug's surprising effect. "We saw many predictable adverse effects ... but one surprise was that the number of dividing cardiomyocytes was slightly increased," said Lum, the study's senior author. For the study, the researchers induced heart attacks in mice, administered a Porcn inhibitor as treatment, and observed that the mice hearts' blood-pumping ability had improved by almost twofold compared to subjects that were left untreated. Rhonda Bassel-Duby, Hamon Center for Regenerative Science and Medicine's associate director and one of the study's authors, said it was striking to see that administering a Wnt inhibitor could significantly improve heart function after a heart attack. Aside from improved blood-pumping ability, the hearts of treated mice also showed reduced fibrosis, or scarring. When an abundance of collagen is present, heart scarring can cause the organ to dramatically increase in size, leading to heart failure. Lum explained that fibriotic responses can have immediate benefits but they can also overwhelm the heart's regeneration ability in the long run. With the drug agent they are developing, he and the rest of the research team believe that they can regulate fibriotic response, which will improve the heart's wound-healing abilities. The Porcn inhibitor will also only require a short usage duration so it may be possible as well to avoid the unpleasant side effects usually attributed to cancer drugs. The researchers are hopeful that they'll be able to conduct clinical trials next year on the Porcn inhibitor to confirm its potential as a regenerative aid for heart disease. Lum and Bassel-Duby were joined by Jesung Moon, Eric N. Olson, Huanyu Zhou, James F. Amatruda, Li-shu Zhang, Noelle S. Williams, Wei Tan, Jian Q. Feng, Ying Liu, Sean P. Palecek, Shanrong Zhang, Xiaoping Bao, and Lorraine K. Morlock in the research. According to the American Heart Association's Heart Disease and Stroke Statistics Update for 2017, cardiovascular disease remains the leading cause of death in the United States, with about 6.5 million American adults suffering from heart failure from 2011 to 2014. The AHA's report also projects this figure will increase by 2030 by 46 percent. Heart failure is defined as a condition where the heart is too weak to normally pump blood through the body. According to the U.S. Centers for Disease Control and Prevention, some 735,000 Americans experience heart attacks each year. Out of all the heart disease types, coronary heart disease is the most common, claiming more than 370,000 people annually. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | November 1, 2016
Site: www.biosciencetechnology.com

Normal, healthy heart muscle is well-supplied with oxygen-rich blood. But UT Southwestern Medical Center cardiologists have been able to regenerate heart muscle by placing mice in an extremely low-oxygen environment. Researchers with the Hamon Center for Regenerative Science and Medicine gradually lowered the oxygen in the air breathed by mice until it was at 7 percent - about the concentration of oxygen at the top of Mt. Everest. After two weeks in the low-oxygen environment, the heart muscle cells - called cardiomyocytes - were dividing and growing. Under normal circumstances cardiomyocytes do not divide in adult mammals. The findings, published in Nature, build upon years of work that began with the discovery that the hearts of newborn mammals have the ability to regenerate, similar to the way skin has the ability to repair itself after a cut. But this ability of heart muscle to regenerate is quickly lost in the following weeks as the animal ages and cardiomyocytes are bathed in the oxygen-rich environment of the beating heart, causing damage to the cells. "The adult human heart is not capable of any meaningful repair following a heart attack, which is why heart attacks have such a devastating impact," said Dr. Hesham Sadek, Associate Professor of Internal Medicine and with the Hamon Center. "Though counterintuitive, we've shown that severely lowering oxygen exposure can sidestep damage to cells caused by oxygen and turn cell division back on, leading to heart regrowth." In the current study, researchers lowered the oxygen level from the normal 21 percent to 7 percent over a period of weeks, then monitored the mass and function of the heart. They demonstrated that reduction in oxygen leads to both an increase in cardiomyocytes and improved heart function. The researchers had tried a 10 percent oxygen environment, but there was no heart regrowth in the 10 percent oxygen environment. To avoid oxygen damage to cells, oxygen levels needed to be very low, a situation referred to as hypoxia. "This work shows that hypoxia equivalent to the summit of Mt. Everest can actually reverse heart disease, and that is extraordinary," said Dr. Benjamin Levine, Professor of Internal Medicine who holds the Distinguished Professorship in Exercise Sciences, and who directs the Institute of Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas, a joint program of UT Southwestern and Texas Health Resources. "In theory, creating a low-oxygen environment could lead to repair not only of heart muscle, but of other organs as well," said Dr. Sadek, who holds the J. Fred Schoellkopf, Jr. Chair in Cardiology. "Although exposure to this level of hypoxia can result in complications, it is tolerated in humans when performed in a controlled setting." The latest findings build upon previous research by UT Southwestern scientists that includes:


News Article | November 1, 2016
Site: www.sciencedaily.com

Normal, healthy heart muscle is well-supplied with oxygen-rich blood. But UT Southwestern Medical Center cardiologists have been able to regenerate heart muscle by placing mice in an extremely low-oxygen environment. Researchers with the Hamon Center for Regenerative Science and Medicine gradually lowered the oxygen in the air breathed by mice until it was at 7 percent -- about the concentration of oxygen at the top of Mt. Everest. After two weeks in the low-oxygen environment, the heart muscle cells -- called cardiomyocytes -- were dividing and growing. Under normal circumstances cardiomyocytes do not divide in adult mammals. The findings, published in Nature, build upon years of work that began with the discovery that the hearts of newborn mammals have the ability to regenerate, similar to the way skin has the ability to repair itself after a cut. But this ability of heart muscle to regenerate is quickly lost in the following weeks as the animal ages and cardiomyocytes are bathed in the oxygen-rich environment of the beating heart, causing damage to the cells. "The adult human heart is not capable of any meaningful repair following a heart attack, which is why heart attacks have such a devastating impact," said Dr. Hesham Sadek, Associate Professor of Internal Medicine and with the Hamon Center. "Though counterintuitive, we've shown that severely lowering oxygen exposure can sidestep damage to cells caused by oxygen and turn cell division back on, leading to heart regrowth." In the current study, researchers lowered the oxygen level from the normal 21 percent to 7 percent over a period of weeks, then monitored the mass and function of the heart. They demonstrated that reduction in oxygen leads to both an increase in cardiomyocytes and improved heart function. The researchers had tried a 10 percent oxygen environment, but there was no heart regrowth in the 10 percent oxygen environment. To avoid oxygen damage to cells, oxygen levels needed to be very low, a situation referred to as hypoxia. "This work shows that hypoxia equivalent to the summit of Mt. Everest can actually reverse heart disease, and that is extraordinary," said Dr. Benjamin Levine, Professor of Internal Medicine who holds the Distinguished Professorship in Exercise Sciences, and who directs the Institute of Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas, a joint program of UT Southwestern and Texas Health Resources. "In theory, creating a low-oxygen environment could lead to repair not only of heart muscle, but of other organs as well," said Dr. Sadek, who holds the J. Fred Schoellkopf, Jr. Chair in Cardiology. "Although exposure to this level of hypoxia can result in complications, it is tolerated in humans when performed in a controlled setting." The latest findings build upon previous research by UT Southwestern scientists that includes:


"These data should promote a re-evaluation of those diseases to see if this new function that we've identified contributes to those defects," said senior study author Dr. Michael Buszczak, Associate Professor of Molecular Biology and with the Hamon Center for Regenerative Science and Medicine at UT Southwestern. The study, published recently in Developmental Cell, indicates that RNA-binding fox (Rbfox) proteins oversee translation of messenger RNA, or mRNA, into proteins. Using the fruit fly Drosophila as a model, researchers showed that the Rbfox1 protein, in particular, has this regulatory role. Rbfox1 proteins were known to play a key role in splicing together coding portions of genes called exons to form mRNA, which is subsequently translated to form proteins. Splicing largely takes place within the nucleus of cells, where many Rbfox1 proteins are found. But there are also variants of Rbfox1 proteins found in the cytoplasm - the portion of the cell outside the nucleus - and the function of those cytoplasmic proteins had not been understood. "We found that cytoplasmic Rbfox1 represses the production of specific proteins," Dr. Buszczak said. The lead author of the study, UT Southwestern Molecular Biology graduate student Arnaldo Carreira-Rosario, found that Rbfox1 binds to specific elements at the ends of mRNA molecules, preventing these mRNAs from being translated into proteins. If Rbfox1 proteins are lost and mRNA is no longer repressed, that could lead to aberrant growth of cells, or cancers. The researchers found that cytoplasmic forms of Rbfox1 were required for germ cell development in Drosophila. "Without this protein, the germ cells are blocked in a very specific stage of differentiation and just linger there. They can't differentiate into mature eggs," said Dr. Buszczak, an E.E. and Greer Garson Fogelson Scholar in Medical Research. This block leads to sterility in female Drosophila and, in other contexts, can result in an inappropriate proliferation of cells, which underlies cancer. Work by co-author Dr. Mani Ramaswami of Trinity College Dublin in Ireland points to a link between the newly identified function of Rbfox1 proteins and neuronal development and function, which could have important implications for a number of the neuronal disorders linked to disruption of Rbfox1. "The idea is that loss of Rbfox1 causes disease by disrupting protein expression, not RNA splicing," Dr. Buszczak said. "If this interpretation is correct, then it has implications for how one would develop therapeutics to treat the disease in question."

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