44CW – Investigation of mechanisms of radiation resistance in advanced patient derived models of glioblastoma

Status: Available
Intern:
Faculty Name: christopher-d-willey-md-phd
Primary Faculty Appointment: UAB
UAB/HA Department: Radiation Oncology
Campus Address: 2232C HSROC (Building 176F)
Telephone Number: (205) 996-4417
Email: cwilley@uabmc.edu or Click to Send E-Mail
For how many summers have you served as a preceptor: 3 or more
CCC Research Area: Neuro-Oncology
Number of hours per week that the preceptor will personally supervise or work with the intern: 3
Other faculty, staff, or graduate students who may help to supervise the intern:
1. Patricia Hicks
2. Joshua Anderson
Title of Project: 44CW – Investigation of mechanisms of radiation resistance in advanced patient derived models of glioblastoma
Project Description:

Glioblastoma (GBM) is the most common and deadly primary brain malignancy. Despite standard of care therapy of maximal safe surgical resection, fractionated radiation treatment and temozolomide chemotherapy, the median overall survival of GBM is only 15 months after diagnosis. These tumors cannot be fully resected and they display both intrinsic and acquired resistance to radiation and temozolomide. For several decades, preclinical radiation research relied on immortalized cancer cell lines grown in high growth conditions (e.g., serum-containing media) which is much different than the tumor microenvironment in GBM patients where tumors develop in relatively harsh growth conditions. Unfortunately, these established cancer cell lines tend to be poor predictors of patient tumors. As such, my lab utilizes a variety of advanced patient-derived models of cancer including patient-derived xenografts (PDX) in mice, spheroid culture, and 3D bioprinted tumor models which better recapitulate the in vivo condition. Moreover, we have characterized a panel of GBM PDX which represent the spectrum of patient tumor biology including groups of tumors that are inherently sensitive to radiation and temozolomide with others displaying inherent resistance. We have also developed acquired resistance models through in vivo selection with either radiation or temozolomide treatment in mouse models. We have performed next generation sequencing and kinomic profiling of these tumors and now have potential targets for overcoming therapy resistance. A summer CARES project will involve either 1) a virtual experience involving in silico examination of molecular and phenotype data for identifying signatures of sensitivity or resistance; or 2) Wet lab experience involving therapeutic testing of spheroid and 3D bioprinted models if in person training is allowed this summer. Ideal candidate would have some experience with either basic cell biology techniques including cell culture or some experience with coding, particularly R or Python.

Project Status: Already up and running
Location of Project: Birmingham, AL (UAB)
Proposed Start Date: May 3, 2021
Proposed End Date: August 6, 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: Brain
Does this project involve human subjects: No
Does this project involve animal subjects: Yes
Duty:
1.

Maintain an up to date electronic lab notebook on LabArchives including log files to highlight activities, notes, protocols, and data

2.

Become familiar with model systems and lab practices. This will occur through training by Dr. Willey, Dr. Anderson, graduate students and lab manager, Patricia Hicks

3.

Prepare data summary/writeup related to work performed

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, Cell Biology, Computer Programming, Laboratory Skills, basic knowledge, Laboratory Skills, advanced knowledge, Molecular Biology, Neurosciences, Scientific Writing Skills, Statistics and Data Management, basic knowledge