RESEARCH UPDATE
TRANSLATIONAL RADIOBIOLOGY MINUTE WITH DR. SUSAN NOZELL
IN WILLEY
LAB To
A TALE OF MEN AND MARCKS
Dr. Chris Willey’ s laboratory studies the role of MARCKS protein in glioblastoma multiforme( GBM), the most common and neurologically destructive tumor within the central nervous system. MARCKS interacts with the cell and the cytoskeleton to regulate processes such as cell shape, movement, and development.
Dr. Willey’ s lab has determined that in GBM, MARCKS levels inversely correlate with tumor growth, and positively correlate with patient survival rate. Unfortunately, some GBM display reduced levels of MARCKS are these tumors are more resistant to radiation therapy. These findings suggest MARCKS may be useful as a new biomarker in GBM and perhaps more importantly, that MARCKS may be useful as a therapy.
“ For an anticancer poison to become a useful drug … it needs [ ed ] to be a fantastically nimble knife: sharp enough to kill cancer yet selective enough to spare the patient.”-Siddhartha Mukherjee, The Emperor of All Maladies: A Biography of Cancer
“ Cancer cells have this‘ quirk’’ we’ re going to use that to kill them.”- Nicholas Eustace
tackle the next hurdle, they collaborated with Dr. Eugenia Kharlempieva, who encapsulated MARCKSp within a nano-bubble. This would allow MARCKS-p to be delivered through the blood and ensure its delivery to the brain; moreover, it would keep MARCKS-p“ hidden” until its release could be triggered using ultrasound, which is inaudible to the human ear. For the purposes of releasing MARCKS-p, ultrasound would be applied to a minimal area for a very short duration.
While still in very early pre-clinical stages, preliminary results are promising, and Investigators are hopeful that these results will translate into meaningful, translational changes for patients with GBM.
Dr. Susan Nozell is an Associate Professor of Pre-Clinical Research.
So how do you“ re-introduce AND program” MARCKS to target and kill GBM? That’ s up to Nick Eustace, a UAB Medical Scientist Training Program( MSTP) student in Dr. Willey’ s lab. Dr. Willey and Nick have identified a“ quirk” within MARCKS … the peptide sequence( MARCKS-p) that can rapidly(< 30 minutes) kill GBM cells, but not normal human astrocytes( Fig. 1).
Fig. 1. MARCKS-p kills GBM cells, but not normal human astrocytes.( Left) Astrocytes are the most abundant cell within the human brain. When grown in culture, they adhere to the plate and form long stellate that give them a“ star-like” appearance. Astrocytes are not harmed upon treatment with MARCKS-p.( Right) Conversely, MARCKS-p rapidly kills GBM cells. This is evident as these cells lose their“ star-like” appearance, round up and become detached from the plate.
So, will MARCKS-p be effective against an entire tumor? To determine this, Dr. Willey and engineered MARCKS-p to fluoresce, or“ glow” under certain wavelengths of light; this would allow them to track MARCKS-p movements both outside and inside the cell( Fig. 2). These findings were important to establish that MARCKS-p could bind to and / or get inside a living cell.
Fig. 2. MARCKS-p can enter into cells. Shown above are normal human astrocytes; their nuclei have been stained blue and their cytoskeleton stained green. MARCKS-p is observed as purple, and can be seen inside the cell above, adjacent to and around the nucleus.
15 | RAYS OF HOPE