Mary Gates Endowment For Students

Targeting von Willebrand factor to model disease in human pluripotent stem cells

Faculty PI:

Hongxia Fu, Ph.D.

Immediate Mentor/Supervisor:

Manasee Kelkar

Project or Start-Up Company Name:

Targeting von Willebrand factor to model disease in human pluripotent stem cells

Lab/Project Website:

www.thefulab.com 

Work Location:

South Lake Union Campus, Room N5420, University of Washington

850 Republican Street, Seattle WA 98109

Work Hours (include recurring team meetings, special events, etc.):

  • 9 AM – 5 PM, all weekdays
  • Lab meeting: 9 AM – 10 AM, every Wednesday
  • Small group meeting for undergraduate research: 1 PM – 2 PM, every Friday

Overall Program Goal:

Overall goals: Utilize human pluripotent stem cells (hPSC) and target von Willebrand factor (VWF) to develop therapeutics to treat blood diseases. 

Von Willebrand factor (VWF), an essential blood protein in hemostasis and thrombosis, is synthesized in endothelial cells (EC) or megakaryocytes and secreted as multimers into blood circulation system. Deficient or defective VWF can cause bleeding disorders, such as von Willebrand disease (VWD), whereas gain of function can cause thrombosis. Human pluripotent stem cell-derived endothelial cells (hPSC-EC) have great potential to study VWF, EC and vascular function, in order to develop novel methods to treat bleeding disorders and thrombosis. We have developed hPSC-EC models and found new reagents/compounds to regulate VWF expression level. In this proposed project, we would like to further characterize (1) the molecular mechanisms and (2) the effects on treating blood diseases of these reagents/compounds.

Intern Project Description and Responsibilities:

The intern will further characterize (1) the molecular mechanisms and (2) the effects on treating blood diseases of the candidate reagents/compounds using hPSC-EC. The intern will work with the PI and the research scientist, Manasee Kelkar, to perform experiment and analyze data in this project, which include cell culture, fluorescence microscopy, cell functional studies, and reagents/compounds efficacy in treating diseases. At the conclusion of the project the intern will compile findings into a powerpoint presentation and present it to the laboratory.

Pre-requisites:

Pre-requisites: cell biology and basic cell culture. The position is open to all academic backgrounds, but previous lab experience and particularly the ability to pipette and conduct cell culture would be helpful. Familiarity with vascular disease is not required but might be helpful as well.

Level of Independence:

The student will work under the direct supervision of the PI and the research scientist, Manasee Kelkar to learn the ropes of the culture system and conduct the work described above, and to design experiments on a weekly basis. The student will be expected to participate in lab meetings on a regular basis and will liaison with others in the lab working to translate these technologies from bench to bedside.

Learning Opportunities:

Cell signaling pathways in drug development, fluorescence microscopy, and microfluidics will be topic areas for enrichment.