UNIVERSITY PARK, Pa. — Xiaojun “Lance” Lian, assistant professor of biomedical engineering at Penn State, has received a $500,000, five-year Early Career Development Program (CAREER) grant from the National Science Foundation (NSF).
Lian will use the grant to potentially solve an issue with large-scale application of stem cell therapy, which uses cells generated from stem cells. Stem cells are undifferentiated cells that can be differentiated into specialized cells such as heart, liver, lung, etc.
These differentiated cells can be used to repair and replace tissues damaged by disease, such as stroke, heart attack and diabetes. However, this approach requires significant numbers of therapeutic cells with known activity, something that is currently difficult to produce.
Lian will use the grant to develop a method of generating large quantities of therapeutic endothelial cells and pancreatic beta cells from stem cells. The pancreatic beta cells could be used for various medical treatments such as stem cell therapy for type 1 diabetes.
“After one single transplantation of these functional beta cells, type 1 diabetes patients may be cured by this cell therapy approach,” Lian said.
The therapeutic endothelial cells could be used for engineering new blood vessels, transplanting endothelial cells into the heart for myocardial regeneration and inducing the body to generate new blood vessels to treat regional ischemia, a restriction of blood supply that can cause tissue damage.
The method Lian is creating to generate therapeutic cells is based on the Synergistic Activation Mediator (SAM). A SAM system consists of a CRISPR dCas9 activator, and its corresponding guide RNA. CRISPR dCas9 is a gene editing tool, using the dCas9 protein which binds itself to a targeted segment of DNA in stem cells. The guide RNA will tell the dCas9 activator where to bind across the human genome in order to achieve targeted gene activation near the binding site.
Currently, there are two main methods of inducing differentiation. One is using growth factors, naturally occurring substances that promote differentiation. The other is using small molecules, which induce differentiation by activating or inhibiting key cell signaling pathways, an important step in changing stem cells into other cells.
“The SAM system would introduce a novel technology, the SAM dCas9 activators, to the stem cell differentiation toolkit in addition to growth factor and small molecule methods,” Lian said.
The NSF CAREER Program supports early-career faculty who have the potential to serve as academic role models in research and education. Activities pursued by early-career faculty should build a firm foundation for a lifetime of leadership in integrating education and research, according to the NSF website.
The educational component of Lian’s CAREER Award will include activities and lab tours designed to engage undergraduate and graduate students. A “Stem Cell and Art” showcase will highlight artistic, technical and ethical aspects of stem cell research. It will be developed for K-12 students, their families and the general public.
“After more than 10 years of stem cell research, I have acquired many beautiful images of different human cells differentiated from stem cells, such as neurons, endothelial cells, cardiomyocytes and pancreatic beta cells,” Lian said. “I will collaborate with the Palmer Museum of Art at Penn State to develop the ‘Stem Cell and Art’ showcase and display it at the museum.”
Lian believes the showcase could be helpful in both educating the public about stem cell research and recruiting students.
“Through this art show, the general public will learn the importance of these cells for curing a variety of diseases,” Lian said. “This will help recruit K-12 students in the science and engineering area and win the general public’s support for continuing national funding in the stem cell research field and more broadly in other science and engineering fields.”