Status: Available
Intern:
Faculty Name: bin-ren-4
Primary Faculty Appointment: UAB
UAB/HA Department: Surgery
Campus Address: WTI630
Telephone Number: (205) 996-2582
Email: bren98@uab.edu or Click to Send E-Mail
For how many summers have you served as a preceptor: 2
CCC Research Area: Cancer Biology & Immunology
Number of hours per week that the preceptor will personally supervise or work with the intern: 2
Other faculty, staff, or graduate students who may help to supervise the intern:
1. Dr Abdellah Akil. Dr Ana Karen
2. Rong Yuan
Title of Project: 24BR – Cancer Stem Cells and Tumor Vascular Microenvironment
Project Description:
Arteriolar endothelial cells (ECs) promote self-renewal of CSCs by direct cell-cell contact via Notch activation or indirect cytokine production. LPA/PKD-1 signaling-mediated arteriolar differentiation of ECs via inducing arterial markers, ephrin B2 and delta-like ligand 4 (DLL4, also a ligand for Notch) and regulation of CD36 (an angiogenesis regulator in ECs) may create the arteriolar niche to enhance BCSC self-renewal capacity. Lysophosphatidic acid (LPA), a lipid signaling mediator, switches microvascular EC (MVEC) to an “arteriolar phenotype” via LPA/PKD-1 signaling and chromatin remodeling-mediated CD36 downregulation, likely contributing to the progression of estrogen positive (ER+) BC. Seminal studies showed that CD36 drives stemness of CSCs and increases their metastatic potential. We have also identified CD36+- and PKD-1+-CSCs in human ER+BC specimens. Notably, we have observed the enrichment of the CSCs in the arteriolar niche. Moreover, LPA antagonist or PKD inhibitor inhibits ER+BCSC self-renewal. We propose that LPA antagonist or PKD inhibitor may maintain or stimulate CD36 expression in tumor-associated ECs (TAECs), and inhibits arteriolar remodeling in the TME and stemness of BCSCs. Our central hypothesis is that LPA/PKD-1 signaling promotes arteriolar differentiation and remodeling and CSC self-renewal in ER+BC and that the use of an LPA antagonist or PKD inhibitor in combination with a CD36 inhibitor can effectively disrupt arteriolar niche and eliminate BCSCs to control tumor metastasis.
Project Status: Already up and running
Location of Project: Birmingham, AL (UAB)
Proposed Start Date: May 3, 2021
Proposed End Date: August 27, 2021
Expected work schedule for intern: Flexible, intern can largely set his or her own schedule (as for students who are instructed how to proceed and are permitted to work independently with weekly guidance) and should contribute full-time effort.
Number of days that the student will be expected to come physically to UAB:
More than 1 day per week (prior to start of the internship, gain appropriate waivers and approvals for the student to be on site)
Category of Project: Laboratory Research
Cancer topic: Breast, Pancreas
Does this project involve human subjects: No
Does this project involve animal subjects: Yes
Duty:
1.
Learn relevant knowledge and techniques
2.
Presentation in the lab meetings
3.
Write and contribute abstracts to academic meetings.
Preceptor will provide intern with access to the following: Office or desk space, Computer and printer, Laboratory work bench space, Supplies needed to complete project, Equipment needed to complete project
Likelihood that intern will be included as an author on one or more publications related to this summer research project: Very likely
Areas in which the ideal candidates will have experience: Biochemistry, Cell Biology, Grant Proposal Preparation, Laboratory Skills, basic knowledge, Pathology, Pharmacology, NONE OF THE ABOVE (just the willingness to learn)
