Seed Grants

Alexander Lichtler
$200,000 Quantitative Analysis of Molecular Transport and Population Kinetics of
Stem Cell Cultivation in a Microfluidic System, Tai-Hsi Fan, principal investigator,
Department of Mechanical Engineering.

Embryonic stem cells are especially sensitive to their growth environment. Maintaining them in a man-made culture medium is difficult, because the physiological conditions that can mimic the natural growth environment are not yet well developed. The project combines engineering principals with biology and analytical chemistry methods to quantify how stem cells grow and respond to environments that are physically and chemically altered. Ultimately, the team hopes to identify the ideal physiochemical conditions for the self-renewal of these cells.

 

 

Alexander Lichtler
$200,000 Lineage Mapping of Early Human Embryonic Stem Cell Differentiation,
Craig Nelson, principal investigator, Department of Molecular and Cell Biology.

In order to use stem cells to their full potential, researchers need to be able to use them to generate medical useful cell types. However, the capacity to do this is limited by the fact that scientists actually know very little about early human embryonic development. Much of the existing knowledge has been inferred from observing the development of embryos in laboratory animals. Thus, in order to understand the behavior of stem cells in embryonic development, it is important to study that development directly. The primary objective of this project is to create a clear picture of human embryonic stem cell differentiation, a “roadmap” that will serve as a guide in the generation of the cells needed for regenerative medicine and cell replacement therapy. 

 

 

$200,000 Embryonic Stem Cell as a Universal Cancer Vaccine,
Bei Liu and Zihai Li, principal investigators, UConn Health Center.

Long before embryonic stem cells were used for genetic and developmental studies, researchers understood that the ways in which they can alter their form and replicate are similar to the ways in which cancer cells grow and proliferate. This study is grounded in the fact that immune systems can recognize antigens, such as proteins, on the surface of tumor cells that have the capacity to stimulate the production of antibodies. Most of the current research on cancer vaccines target these antigens. The researchers aim to explore the potential for using stem cells to provide a universal cell-based vaccine against cancer.

 

$200,000 Generation of Insulin Producing Cells from Human Embryonic Stem Cells,
Gang Xu, principal investigator, Center for Regenerative Biology.

The purpose of this study is to compare mouse and human embryonic stem cells in order to better understand how stem cells can be differentiated into insulin producing beta cells. Studies in laboratory mice have demonstrated that it is possible to differentiate stem cells into insulin producing cells and restore normal insulin production once they are transplanted. The long-term goal of the study is to develop patient-specific nuclear transfer embryonic stem cells that effectively treat diabetes without immunosuppression.

 

$200,000 Development of Efficient Methods for Reproducible and Inducible Transgene Expression
in Human Embryonic Stem Cells, James Li, principal investigator, UConn Health Center.

Human embryonic stem cells (hESCs) are an unlimited source of precursor cells that can be directed to differentiate into any types of cells, which can then be used for regenerative medicine and studies of toxicology and pharmacology, the studies of poisons and drugs. How quickly and how efficiently researchers will be able to use hESCs depends upon their capacity to conveniently modify the development of hESCs into various cell types as desired. Current techniques are inefficient and may produce unpredictable results that limit their utility. The purpose of this project is to use an enzyme called DNA recombinase to recognize specific DNA sequences in a specific position in the human genome and then efficiently replicate them to compel stem cells to develop according to specific requirements.

 

$200,000 Pragmatic Assessment of Epigenetic Drift in Human ES Cell Lines,
Theodore Rasmussen, principal investigator, Department of Animal Science.

While they hold enormous promise for the future of healthcare, human embryonic stem cell lines can be very challenging to culture. They can undergo unexpected and irreversible changes that can render them useless for either therapies or further research. Reliable stem cell lines can lose their ability to form a variety of cell types or they can undergo undesirable differentiation in the course of cell culture. This study is exploring epigenetics, influences on gene expression that do not involve changes in the underlying sequence of DNA. One current theory holds that human stem cells undergo “epigenetic drift,” a poorly understood phenomenon that alters gene expression in the cells without the accumulation of DNA-based mutations. Since there is no reliable or simple method to monitor the epigenetic quality of stem cell lines, drift is usually detected only after the cells fail to perform as expected. The aim of the study is to test a new technology developed for assessing the epigenetic status of cells and, further, to try to understand why epigenetic drift occurs. If successful, the research will make the culture and maintenance of human embryonic stem cells a much more reliable process and decrease the time required to bring stem cell-based therapies to the clinic. 

 

$200,000 Cell Cycle and Nuclear Reprogramming by Somatic Cell Fusion,
Winfried Krueger, principal investigator, UConn Health Center.

Somatic cells, any of the cells in a plant or animal except the reproductive cells, can be reprogrammed to acquire stem cell properties by fusing them with embryonic stem cells.

Nuclear reprogramming is the restoration or recreation of the correct pattern of genes in a nucleus derived from a somatic cell. However, a number of factors related to cell cycle, may impact nuclear reprogramming and significantly impact the rate of conversion of cells, depending upon what procedure is used. The project aims to examine these processes.