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Ph.D. in Biomedical Science: Thematic Research Areas Information on this page is excerpted from the University of Connecticut Stem Cell website,
http://stemcell.uconn.edu/index.php.
Stem Cell Research
In 2006, responding to the federal restrictions on the creation of new
stem cell lines for research, the Connecticut General Assembly passed
legislation that was signed into law by Gov. M. Jodi Rell, authorizing
the use of public funds to finance human stem cell research. The law
commits $100 million over a period from 2007 to 2017 to support this
highly promising area of bioscience research.
While five states have passed similar legislation, Connecticut, has set
a new standard by becoming the first state to actually implement a
structured, ongoing research grant program of this type. The law
established a competitive process for awarding research grants. An
impartial Stem Cell Research Advisory Committee, chaired by the
Connecticut Commissioner of Public Health, was appointed to distribute
the funds based on the scientific, legal and ethical integrity of the
research being done.
The first allocation of funds - totaling nearly $20 million - was
disbursed on November 21, 2006. Fifteen of the 21 research proposals
funded were awarded to UConn faculty. Collectively, they amounted to
nearly $12 million, or about 60 percent of the total disbursal for 2007.
The funding supports investigators engaged in a wide range of research
projects designed to unlock the secrets of stem cells and turn them into
effective treatments for a host of diseases and disorders as quickly as
possible.
Below please find a listing of UCHC faculty that received State of
Connecticut Stem Cell Awards along with a brief description of their
research projects.
H. Leonardo Aguila
FACS isolation of progenitors and generation novel cell surfaces
antibodies.
In order for researchers to use stem cells for regenerative therapies,
the design of methods for the correct identification of stem cells is
crucial. One of the best approaches - not only to characterize different
cell types, but also to isolate them - is the generation of antibodies
against cell surface molecules. The Project 2 group has developed unique
tracking systems for musculoskeletal development to visualize progenitor
cells with the ability to develop into cartilage, bone, fat and muscle.
These systems employ genetic techniques that add genetic information to
embryonic stem cells to make them express fluorescent protein at defined
stages of their development.
Gordon G.
Carmichael and Asis Das
DsRNA and Epigenetic Regulation in Embryonic Stem Cells
Embryonic stem cells are endowed with two remarkable features. They have
the capacity for self-renewal and to grow indefinitely, and they also
have pluripotency, the potential to change into virtually any cell in
the human body. The goals of the project are to explore the key
molecular factors that govern “stemness,” and to develop technologies
that will allow manipulation of stem cells and their genes.
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Stephen Clark
Correction of dermal lesions with hES derived progenitor cells
The goal of the project is to develop and test mice models utilizing
human embryonic stem cells in the treatment of skin wounds. The work
done in Project 9 is based on the hypothesis that embryonic stem cells
can participate in and/or improve the skin wound healing process leading
to a better resolution.
A. Jon Goldberg and
Liisa T. Kuhn
Scaffolds to hold and mold progenitor cells at a site of tissue
regeneration.
Most of the projects in the grant focus on particular kinds of tissues
and learning how stem cells progress toward their final tissue types,
including identification of the essential “signaling molecules” that
direct the cells’ development, as well as other necessary environmental
factors. As those questions are answered, the knowledge will be
transferred to the biomaterials scaffolds project, where methods for
practical clinical application will be developed.
Traditional reparative procedures for lost or damaged limbs use
prosthetics, such as the implants used in a hip or knee replacement,
made of metal, ceramic and plastic biomaterials. These prostheses are
meant to replace the damaged tissue or organ, not to repair it.
Cell-based therapies, on the other hand, require reabsorbable
biomaterials. They must carry in the cells and define and shape the area
of regeneration, but they must also degrade or reabsorb so that newly
grown tissues can replace them. These types of biomaterials are called
scaffolds and they are porous, like sponges, so that the cells can be
contained inside the pores. Their purpose is to mimic the natural
environment inside the body in which cells are accustomed to living.
When biomaterials are made this way, they provide a means of triggering
the cell to start regenerating the lost or damaged tissue. For the stem
cell project, the biomaterials group will synthesize novel scaffolds
designed specifically for musculoskeletal system regeneration.
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Brenton R. Graveley
Alternative Splicing in Human Embryonic Stem Cells
In order to fully understand how human embryonic stem cells work and to
develop the ability to differentiate them into specific cell types, it
is essential to determine which genes and proteins are expressed in stem
cells. While many studies have been conducted to clarify which genes are
expressed in stem cells, all of them have overlooked an important aspect
of gene expression - alternative splicing, the process by which a single
gene can give rise to multiple proteins by cutting and pasting the RNA
produced by the gene in different ways. The study will aim to full this
research gap.
Robert A. Kosher and
Caroline Dealy
Generation of cartilage from hES derived progenitor cells.
Degenerative diseases of cartilage are among the most prevalent and
debilitating chronic health problems in the United States, and one of
the main causes of decreased quality of life in adults. While more than
90 percent of the population over age 40 have some form of cartilage
degeneration, treatment is particularly challenging because of the
limited capacity of cartilage for self-repair and renewal. Human
embryonic stem cells are a potentially powerful tool for repair of
cartilage defects and one of the major goals of the Project 7 team is to
develop culture systems and conditions that will allow stem cells to
uniformly differentiate into chrondrocytes, cells that form cartilage.
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Marc Lalande
The role of epigenetics in disease and development
The Lalande lab is currently studying Angelman syndrome (AS), one of
the better-known causes of mental retardation. AS is a neurogenetic
disorder passed exclusively through the maternal germline because of the
epigenetic process called genetic imprinting. Individuals with AS fail
to inherit a normal active maternal copy of the gene encoding ubiquitin
protein ligase E3A (UBE3A). Only the maternal copy of UBE3A is active in
brain with the paternal copy being silenced due to imprinting.
The loss of UBE3A in the brain of AS patients causes the accumulation
of proteins in the brain that result in the clinical problems in AS. The
accumulating proteins have not yet been discovered, and the Lalande lab
is attempting to identify the targets of UBE3A. For these studies, the
Lalande lab has developed techniques to knockout UBE3A in stem cells and
then produce neurons from the UBE3A-negative stem cells. The researchers
are also investigating the molecular process that silences the paternal
UBE3A allele in the brain using a mouse model of the disease. This work
is supported by the Physicians Health Services endowment.
James Li
Development of Efficient Methods for Reproducible and Inducible
Transgene Expression in Human Embryonic Stem Cells
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.
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Zihai (Zack) Li
and Bei Liu
Embryonic Stem Cell as a Universal Cancer Vaccine
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.
Alexander Lichtler
Directing ES Cells to a common progenitor cell for musculoskeletal
tissue generation
The researchers are striving to develop a method that will use
well-defined culture conditions to promote differentiation of human
embryonic stem cells into a pure population of mesoderm cells, cells
from the embryonic layer that ultimately develops into all connective
tissue, muscle, bone and the urogenital and circulatory systems. Those
cells would then be used by other members of the grant team to
differentiate into the type of cells they are studying. Additionally,
the Project 1 group will be aiding Dr. Mina (Project 6), producing
embryonic stem cells equipped with fluorescent protein markers that come
on when the cells have reached a certain differentiation stage.
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Mina Mina
Generation of bone via the neural crest development pathway
The cells that contribute to the facial skeleton, including the bones
and teeth, are formed from cells of the cranial neural crest, the part
of the embryonic ectoderm that develops into the skull, spine and
associated nerves. There is a significant body of scientific evidence
suggesting that differences in embryonic origin and mode of
ossification, the natural formation of bones, in the bones of the face,
skull and spine have significant influences on various properties of the
skeletal tissues at those different sites. Consequently, effective
cell-based therapies for skeletal tissues in the skull and face depend
upon the capacity to identify and isolate stem cells capable of
appropriately regenerating skeletal tissues. Project 6 aims to develop
ways to generate and identify those cells.
David Rowe
Optimizing mesoderm derived bone cell differentiation from hES cells
The project will give researchers who have experience working with mice
stem cells directed to bone cell differentiation the opportunity to
apply their knowledge to human embryonic stem cells. The research aims
to provide objective criteria for evaluating the potential of cells to
develop in bone tissue types with the goal of maximizing the potential
to efficiently differentiate cells to produce bone tissue.
Ren-He Xu
ChIP-chip Analysis to Screen Target Genes of BMP and TGF
Signaling in Human ES Cells
The project extends earlier research through which two essential
signaling pathways have been identified that governs the early fates of
human embryonic stem cells. One of these pathways promotes the cells to
differentiate, while the other sustains their self-renewal. The research
will seek to identify genes that regulate both pathways.
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Additional faculty conducting research in the area of
Stem Cells include:
Stephen J. Crocker, Assistant
Professor of Neuroscience, Ph.D., University of Ottowa.
Stem cells; glia; metalloproteinases; cytokines; development; pathology;
tissue culture.
Xuejun (June) Li,
Assistant Professor of Neuroscience, Ph.D. Fudan University.
Stem cells; neural development and degeneration.
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Read the UCONN Health Center magazine
feature article
on UCHC stem cell research:
"Unlocking
the Secrets of Embryonic Stem Cells"
(PDF, 2MB)
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