2009 State Stem Cell Funding
$1.9 Million – Human ES Cell Core at University of Connecticut and Wesleyan University.
Ren-He Xu, Principal Investigator, UConn Health.
The funds will be used to extend and enhance the work of the UConn Stem Cell Core Laboratory, which is critical to the success of all the projects funded. The funds will make it possible for the laboratory to continue current services supporting research on human embryonic stem cells; support research on induced pluripotent stem (iPS) cells by providing training or direct services for iPS derivation and characterization, and continuing to derive, bank and distribute normal and diseased iPS cells; and enhancing current services by providing state-of-the-art deep sequencing technologies for detailed analysis of both human ES and iPS cell lines derived in the Core.
$500,000 – Williams Syndrome Associated TFII-I Factor and Epigenetic Marking-out in Human ES Cells and Induced Pluripotent Stem (iPS) Cells.
Dashzeveg Bayarsaihan, Principal Investigator, Reconstructive Sciences, UConn Health.
Williams syndrome (WS) is a complex disorder with distinctive features that include craniofacial defects, mental retardation, microcephaly and short stature. Recent findings have pointed to the gene GTF21 as the prime candidate gene responsible for WS. The TFII-I factor is a product of GTF21. It regulates a set of enzymes and it is thought that TFII-I deficiency might disturb embryonic development. The researchers hypothesize that TFII-I is required for maintaining the correct special and temporal expression of a specific subgroup of epigenetic marker genes. The purpose of the project is to investigate epigenetic – that is, changes in gene expression – marking-out in the WS-derived iPS cells.
$500,000 – Mechanisms of Stem Cell Homing to the Injured Heart.
Linda Shapiro, Center for Vascular Biology, UConn Health.
Stem cells have the amazing capacity to contribute to the growth and healing of many different types of tissues. This ability is critically dependent on the cells successfully finding the damaged tissue and effectively incorporating into the site. Currently, stem cells are generally injected into the site of an injury to increase the chances of correct cell delivery, but injection into the heart is quite invasive and carries a certain degree of risk. Stem cell therapy would be greatly simplified if the cells could be injected into the bloodstream and allowed to “home,” or find their way to the damaged tissue. It is known that both the blood vessels of injured tissues and the traveling stem cells display a number of unique molecules on their surfaces that allow them to recognize and attach to each other to begin the process of integrating the stem cells into the damaged tissue. Interestingly, stem cells will bypass healthy blood vessels that lack these special molecules as they search for vessels with the correct “address.” This prevents incorrect positioning. A few of these special molecules have been identified, but stem cell homing is so complex that more of them must exist in order to regulate this intricate process. The researchers have identified a molecule – CD13 – that is found in damaged heart vessels following myocardial infarction (a heart attack) as well as on stem cells of many lineages. CD13 could serve as a recognition molecule and, indeed, the researchers have observed that it participates in the attachment of other types of circulating cells to blood vessels. The researchers have devised a method to improve CD13’s ability to influence circulating cells to recognize and attach to injured blood vessel walls. Using that method, the researchers will investigate the role CD13 plays in stem cell homing to the injured heart and their capacity to enhance homing.
$500,000 – Therapeutic Differentiation of Regulatory T Cells from iPS for Immune Tolerance.
Zihai Li, Department of Immunology, UConn Health.
One of the main challenges of the body’s immune system is to maintain a fine balance between the simultaneous tasks of fighting against germs, but not damaging healthy tissues. Scientists have found that this balance is managed, in part, by a key regulatory T cells called Tregs. Bearing a unique gene, Foxp3, Tregs can suppress self-reactive immune responses and they have emerged as a promising therapeutic tool for autoimmune diseases such as diabetes, lupus, arthritis and inflammatory bowel diseases. The purpose of this research is to generate regulatory T cells from stem cells for treatment of autoimmune diseases. The researchers will derive Tregs from both human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPS cells). To date, no study has specifically addressed the issue of Treg development from stem cells. Moreover, this is the first in-depth study to compare Tregs generated from different sources of stem cells.
$500,000 – Prevention of Spontaneous Differentiation and Epigenetic Compromise in Human ES Cells and iPS Cells.
Theodore Rasmussen, Center for Regenerative Biology, UConn.
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPS cells) are of great promise for medicine because they can be coaxed to differentiate into all cell types in the human body. However, both hESCs and iPS cells frequently undergo spontaneous and irreversible alterations during their culture in vitro. Those alterations are often epigenetic in nature, meaning that though the DNA sequence may remain unaltered, gene expression becomes mis-regulated. This compromises the quality of the cells and their usefulness for clinical applications. The object of this research is to identify methods and chemical compounds that can prevent the spontaneous loss of quality of hESCs and iPS cells.
$500,000 – Development of iPS Cells to Study Craniometaphysical Dysplasia in Humans.
Alexander Lichtler, Department of Reconstructive Sciences, UConn Health.
Craniometaphyseal dysplasia (CMD) is a rare and debilitating bone disorder with sometimes fatal overgrowth of skull bones. There is currently no treatment for this disorder. It affects children and progresses throughout life. Research using rodent models has been promising, but it is currently impossible to translate the findings to the human system because bone cells from craniometaphyseal dysplasia patients only rarely become available. Thus, the purpose of the project is to develop and investigate inducible pluripotent stem cells from patients with CMD. The research aims to generate a thorough understanding of how to stimulate stem cells to become osteoblasts, cells that produce bone tissue; how to do quality assessments of differentiating human embryonic stem cells and inducible pluripotent stem cells; and what the differences are between patient and control osteoblasts.
$200,000 – Hybrid Peptide/RNA Molecules for Safe and Efficient Gene Silencing in Human Embryonic Stem (ES) Cells.
Yong Wang, Principal Investigator, School of Engineering, UConn.
Small interfering RNA (siRNA), which is also known as “short interfering RNA” or “silencing RNA,” is a class of RNA molecules that interfere with the expression of specific genes. They are of critical importance in human embryonic stem cell (hESC) research, but current methods used for their delivery into hESCs have many limitations. The purpose of the research is to develop novel hybrid molecules that address those limitations, facilitating efficient siRNA delivery.
$200,000 – Can Natural Neuromodulators Improve the Generation of Nerve Cells from Human Embryonic Stem Cells?
Srdjan Antic, Department of Neuroscience, UConn Health.
Parkinson’s disease is caused by the degeneration and death of a small group of neurons called dopaminergic neurons that release an important substance dopamine. It is a neurotransmitter that plays an important role in behavior, cognition, motor skills and many other brain functions. Human embryonic stem (hESC) cells may serve as a renewable source of neurons. Indeed, several research groups have been able to grow dopamine-releasing neurons in laboratories and then transplant them into an animal model of Parkinson’s disease. Several obstacles, however, must be surmounted before this can become a treatment for Parkinson’s. The research will explore a novel method for improving the procedures for nerve cell generation from hESC using natural neuromodulators, whose positive effects on neuron proliferation, migration, differtiation and maturation are well known.
$200,000 – A Human Cell Culture Model of Angelman Syndrome for Drug Screening.
Stormy Chamberlain, Department of Genetics and Genome Sciences, UConn Health.
Angelman syndrome (AS) is a human neurodevelopmental disorder that causes mental retardation, lack of speech, ataxia (the inability to coordinate muscle movements) and seizures. The purpose of the research is to develop a human neuronal cell culture model to study and develop therapies for this devastating disorder. Researchers will use two different pluripotent stem cell lines generated to model AS. The cells will be differentiated into neurons in order to determine how the AS gene is regulated during human neuronal development. With a cell culture to study, researchers will screen for drugs that may be useful in treating Angelman syndrome.
$200,000 – Novel Aspects of RNA Editing in Human ES Cells.
Ling-Ling Chen, Department of Genetics and Genome Sciences, UConn Health.
RNA editing is the process through which the genetic information in molecule of RNA is chemically changed. It is known that RNA editing plays a role in inhibiting gene expression in some instances. The purpose of this project is to understand how this complex cellular process impacts human embryonic stem cells and to clarify the role of RNA editing in the maintenance of self-renewal and pluripotency, stem cells’ capacity to become many different kinds of tissue.
$200,000 – Evaluation of Homologous Recombination in Human Embryonic Stem Cells and Stimulation Using Viral Proteins.
April Schumacher, Department of Molecular, Microbial and Structural Biology, UConn Health.
Gene targeting is a process that alters genes through recombination, the introduction of replacement genetic material. A number of targeting methods have been developed, but knowledge of cellular pathways – the chemical sequences that change cell behavior, and can result in disease – is still quite limited. In order to use stem cells therapeutically, researchers will have to target specific genes to generate the modified cells that will be required. The purpose of this project is to improve gene targeting in human embryonic stem cells in order to capitalize on the potential of embryonic stem cells to treat human injury and disease.