Status: Filled – Intern: Ruth Mokua
Intern: Ruth Mokua
Faculty Name: bin-ren-2
UAB Department: Surgery
UAB School: Medicine
Campus Address: WTI630
Telephone Number: (205) 996-2582
Email: bren@uabmc.edu or Click to Send E-Mail
For how many summers have you served as a preceptor: 1
CCC Research Area: Cancer Biology
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. Ana Karen Gutierrez
2. Gloria Yuan
Title of Project: 48BR – Role of Arteriolar Differentiation in Breast Cancer Metastasis
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 4, 2020
Proposed End Date: August 28, 2020
Expected work schedule for intern: Not very flexible, intern MUST be at work on certain days of the week and at certain times of the day (as may be necessary to interview patients, attend lab meetings, process samples, etc.) and should contribute full-time effort.
Category of Project: Laboratory Research
Cancer topic: Breast
Does this project involve human subjects: Yes
Does this project involve animal subjects: Yes
Duty:
1.
Perform breast cancer cell and endothelial cell culture and study the molecular mechanisms
2.
Learn how to design experiments and interpret data, and prepare presentation
3.
Present the research results in the lab meeting and present a poster in UAB meeting or national meeting if possible.
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:
Animal Research, Biochemistry, Cell Biology, Molecular Biology, Pathology, Pharmacology
