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