CLAS scientists get stem cell grants

Four biologists in CLAS and a researcher with a joint appointment in the College are among the 70 scientists awarded the first grants from the State of Connecticut’s Stem Cell Research Fund.

In all, 23 researchers from UConn received 15 grants totaling more than $12 million of the nearly $20 million allocated from the state fund, which was established in 2005. Scientists from Yale and Wesleyan also received grants.

Another CLAS faculty member, Anne L. Hiskes, associate professor of philosophy, chairs a new committee that will provide ethical oversight of all of the UConn grants.

Akiko Nishiyama, associate professor of physiology and neurobiology (PNB), is the principal investigator on a four-year, $530,000 project to investigate the ability of different types of glial cells generated from human embryonic stem cells to promote regeneration in the brain.

Glial cells, which Nishiyama has studied extensively, differ from neurons, the signaling cells of the brain. They are thought to support the function of neurons, and some types of glial cells can promote the development of axons, which are extensions of neurons.

When there is damage to the brain or spinal cord, axons are severed and are difficult to re-grow. The researchers want to see whether glial cells developed from human embryonic stem cells could be used to support axon regeneration.

Nishiyama said that initial work has been done on mouse glial cells by Christopher Brunquell, an undergraduate with a double major in chemical engineering and structural biology/biophysics who works in her laboratory. Polylactic acid scaffolds that are used to hold the glial cells have been developed with the help of Richard Parnas, associate professor and director of the chemical engineering program.

Joseph LoTurco, professor of PNB, was awarded a four-year, $562,000 grant from the stem cell fund to study the genes that control the migration of stem cell-derived neurons in the brain.

In order to be useful in treating degenerative and traumatic brain disorders, embryonic stem cells that develop into neurons must be able to locate themselves in the correct area of the brain, he noted. They can’t be injected directly to every location where they are needed in this complex, solid tissue, and “it’s going to be a challenge to get them to disburse to the right places,” LoTurco said.

LoTurco’s research group has studied the genes that direct neurons to migrate in normal development. He will now use the same technology to study how stem cell replacement neurons may be coaxed to travel and integrate into the appropriate places.

David Goldhamer, associate professor of molecular and cell biology, is a member of the research team on one of two multi-investigator grants funded by the state. The $3.5 million, three-year project, headed by Dr. David W. Rowe of the UConn Health Center, will study how embryonic stem cells might help rebuild bone, cartilage, skin, and muscle tissue.

Goldhamer, who is a muscle developmental biologist, said little is known about the ability of embryonic stem cells to regenerate musculoskeletal tissues. The goal of the research will be to understand how to get embryonic stem cells to differentiate into cartilage, skin, bone, and muscle cells.

He is interested in the potential application of the research in treating muscular dystrophy and injuries.

Goldhamer and Rowe learned they had similar interests when they both worked on the provost’s stem cell working group, established at UConn last year. The goals of the group are to work with senior administrators to assess infrastructure needs for stem cell research, to establish policies for grant submissions to the state, and to keep faculty informed of state policies and procedures as they develop.

The group also is working to foster collaborative, cross-campus research and to develop a future organizational structure for the UConn Stem Cell Institute. It helped to recruit Dr. Ren-He Xu from Wisconsin to serve as director of the UConn stem cell core facility, which was established last year.

Two-year seed grants were awarded from the state stem cell fund to two biologists in CLAS. Theodore Rasmussen, assistant professor of Animal Science who has a joint appointment in the Department of Molecular and Cell Biology in CLAS, will study the maintenance of pluripotency, a property of embryonic stem cells that allows them to develop into any type of cell.

Over time, stem cell cultures can spontaneously lose their pluripotency, Rasmussen said. He will study at the molecular level how this happens and analyze it quantitatively so that human embryonic stem cell cultures can be maintained without the loss of pluripotency.

Rasmussen also has a previously awarded $1.4 million federal grant to study mouse embryonic stem cells.

A $200,000 seed grant was also awarded to Craig E. Nelson, assistant professor of molecular and cell biology, to map the events leading to the production of different, therapeutically relevant cell types from human embryonic stem cells.

This “roadmap” will serve as a key guide in generating the cells needed for regenerative medicine and cell replacement therapy. Stem cell cultures are complex mixtures of many different cell types, presenting obstacles to systematically studying the development of individual cells. Nelson’s lab uses single-cell analysis methods to track the identity of individual human embryonic stem cells as they develop and differentiate in a cell culture.

Anne L. Hiskes, associate professor or philosophy, is chair of UConn’s Embryonic Stem Cell Oversight Committee (ESCRO), which has ethical oversight of the University’s human stem cell research. She is also on the bioethics subcommittee of the state Stem Cell Research Advisory Committee, which awarded the grants, and she is a member of UConn’s stem cell working group.

ESCRO will review all of the UConn research to make sure it is justified and appropriate. The state subcommittee is trying to create broad policies for the state and coordinated ethical oversight across institutions, Hiskes said.