Hollings Cancer Center 12th Annual Research Retreat
Thursday, November 15, 2012
5:15 pm – 8:30 pm, Room 110 Bioengineering Building
and
Friday, November 16, 2012
8:30 am – 4:00 pm, Daniel Island Club
The Hollings Cancer Center announces its annual call for pre-doctoral students, postdoctoral
fellows, residents, fellows and new junior faculty (recruited from outside MUSC within the last
two years) to submit cancer research abstracts to be disseminated at the 12th Annual Research
Retreat. Up to fifteen individuals who submit abstracts will also be invited for an oral
presentation.
Abstract Submission:
E-mail abstract as an MS Word document file to boehrigp@musc.edu by 5:00 pm Monday,
October 15th. Please use the format of the attached sample. Abstracts will be reviewed by HCC
Leadership on the basis of their scientific content, including: cancer significance of research,
novel research aims and methods. Up to 15 abstracts will be selected for oral presentation on
either Thursday or Friday. Authors whose abstracts are selected for oral will be notified by
Monday, October 29th. All submitted abstracts will be printed in the retreat booklet. Abstracts
not selected for oral presentation will be part of the poster presentation on Thursday or Friday.
From the selected oral presentations, two will be chosen to receive a professional travel stipend
from the Cato Fellowship.
ABSTRACT COVERSHEET
Submitter Name:
__Pre-Doctoral
_____________________________________
__ Post-Doctoral __Clinical Resident/Fellow
__ Junior Faculty (less than 2 years)
PI/Sr. Investigator:
Other Collaborators:
Project Title:
Department:
Funding Source Name/Number (e.g., NCI R01CA123456):
Abstract Narrative: Summary description of research project in 300 words or less (single-spaced, 12
point Times New Roman). Sample attached.
Please check all HCC Supported Shared Resources used in project:
__Cancer Biostatistics __ Cell/Molecular Imaging
__Cellular Therapy
__ Gene Targeting/Knockout
__Clinical Trials
__ Drug Discovery
__ Drug Metabolism/Pharm
__ Flow Cytometry/Cell Sorting
__Lipidomics
__ Biorepository
__Translational Laboratory
__ Small Animal Imaging
Please check all the descriptors that apply for your submitted abstract:
__Breast Cancer
__ GU Cancer
__Sarcoma
__Melanoma
__GI Cancer
__Hem Malignancy __Neuro
__Other___________________________________
__Laboratory/Basic Science
__Population Studies
__Clinical/Translational Science
__Pediatric Cancer
__Thoracic Cancer
__ Head/Neck
(Single-spaced, 300 words or less 12 point Times New Roman)
Different roles of Sphingosine kinase isoenzyme in cancer cells and characterization of
SphK isoenzyme selective inhibitors
Peng Gao, Yan Zhuang and Charles D. Smith
Department of Pharmaceutical and Biomedical Sciences
Funding Source Name/Number: NIH R01CA123456
Two Sphingosine kinases (SphKs) isoenzymes, SphK1 and SphK2, play only partially
overlapping roles in tumor epithelial cells proliferation and migration although both of them
catalyze the formation of sphingosine-1-phosphate. Our genetic approach (siRNA) in multiple
cancer cell lines revealed that SphK2 knockdown had more inhibitive effects on cancer cell
proliferation and migration than SphK1 knockdown. Both qPCR and a novel florescence-based
HPLC method measuring SphK activities confirmed the increased SphK1 induced by SphK2
knockdown could not rescue the cells from apoptosis. Western results showed SphK2 ablation
has different effects on several key cell survival pathways including p21, p53, FAK, VCAM1.
Most surprisingly, knocking down SphK2 decreases not only expression but also activation of
ERK2 compared to less effects caused by SphK1 ablation. However, as the dominant isoenzyme,
SphK1 ablation did increase the total amount of ceramide species. In order to confirm the results
from the genetic approach, we developed pharmacological approaches that used SphK
isoenzymes selective inhibitors to dissect the functions of SphK isoenzymes. After the structure
optimization of the lead compounds identified by high throughput screening, two compounds
were identified as SphK inhibitors: 3-(4-Chlorophenyl) adamantane-1-carboxylic acid (pyridin4-ylmethyl) amide hydrochloride salt - termed ABC294640 and 3-(4-Chlorophenyl) adamantane1-carboxylic acid [2-(3, 4-dihydroxyphenyl) ethyl] amide – termed ABC294735. The inhibition
specificities of these compounds were characterized. ABC294640 is a SphK2 selective inhibitor
(Ki 10μM), while ABC294735 (Ki SphK1 2.5μM, Ki SphK2 3.5μM) is a dual inhibitor. LineweaverBurk plots using the data from recombinant SphK1/2 active enzymes and kinase assay kit
revealed ABC294640 and ABC294735 were SphK competitive inhibitors. A possibly SphK1
selective inhibitor had also been identified, but kinase profiling data revealed it as a paninhibitors for several important kinases.
HCC Shared Resources used: Drug Discovery, Flow Cytometry/Cell Sorting, Lipidomics