Seminar - Brain Tumor Stem Cells – Do They Exist and Are They Therapeutically Relevant?
Date: October 30, 2009
Time: 4:00 PM
Location: Matheson Hall, Room: 109
Speaker(s):
Justin Durla Lathia, Ph.D.
Department of Stem Cell Biology and Regenerative Medicine
Cleveland Clinic, Cleveland, OH
Details:
Tumors can be considered aberrant organ systems in that they contain a complex interplay between the neoplastic compartment and recruited vascular, inflammatory, and stromal elements. Many cancers display a hierarchy of differentiation states within the tumor cells. In addition, molecular signals that drive tumor formation and maintenance commonly overlap with those involved in normal developmental processes and wound responses. It is therefore not surprising that cancers invoke and utilize stem cell programs that promote tumor malignancy. Stem cell-like cancer cells (or cancer stem cells) need not be derived from normal stem cells but may be subjected to evolutionary pressures that select for the capacity to self renew extensively or differentiate depending on conditions. Cancer stem cells have been derived from several brain tumors, including Glioblastoma Multiforme (GBM) the most common primary brain tumor, which has a 5 year survival rate of less than 3% and appears to be resistant to conventional therapies As cancer stem cells are defined in functional assays of tumor initiation, significant efforts will be needed to elucidate the models that best replicate the cellular demands for these cells to be maintained and grow. Like somatic stem cells, cancer stem cells reside in specific niches (perivascular and hypoxic) and non-stem cells may be reprogrammed towards a stem cell state through microenvironmental conditions. We and others have demonstrated that brain tumor stem cells are resistant to conventional therapy but may be sensitized through molecularly targeted therapeutics. GBMs are highly vascular cancers for which anti-angiogenics have shown clinical activity. We previously demonstrated that brain tumor stem cells promote tumor angiogenesis and we are now dissecting the specific molecular drivers for these effects. In addition, we are identifying signaling pathways and molecules that may have promise in disrupting brain tumor stem cell self renewal and survival, including Akt, L1CAM, c-myc, interleukin-6, and hypoxia inducible factor-2α. Application of the cancer stem cell hypothesis may translate into improved diagnostic, prognostic, and therapeutic approaches for brain tumors.
WATCH WEBCAST
Biosketch:
Justin D. Lathia, Ph.D., is postdoctoral researcher in the Department of Stem Cell Biology and Regenerative Medicine at the Lerner Research Institute, Cleveland Clinic, Cleveland, OH. He earned his bachelor’s and master’s degree at Drexel University (magna cum laude) in 2003, majoring in Biomedical Engineering. Justin received in Ph.D. in 2008 from Cambridge University through the NIH-Cambridge Graduate Partnership Program where he studied Neurology and Stem Cell Biology.
While at Drexel University, Justin completed his master’s thesis with Dr. Margaret A. Wheatley. He designed ultrasound contrast agents for targeted breast cancer imaging via integrins, extracellular matrix cell surface receptors. Justin continued his work on integrins during his Ph.D. which he completed with Prof. Charles ffrench-Constant, Dr. Maeve A. Caldwell, Dr. Mahendra S. Rao, and Dr. Mark P. Mattson. While working on his Ph.D. thesis, Justin showed a novel role for integrins in regulating neural stem cell behavior in the embryonic and adult CNS, disruption of which alter brain formation which as recently been published in PLoS Biology.
In June of 2008, Justin joined the lab of Dr. Jeremy Rich (first at Duke University in Durham, NC and then moved with Dr. Rich to the Cleveland Clinic in January of 2009) and has been working on brain tumor stem cells. His work involves the role of the tumor microenvironment on brain tumor stem cell regulation. In addition, he has designed and implemented a single cell analysis platform for the analysis of cell fate choice by brain tumor stem cells. He has recently received fellowships from the American Brain Tumor Association and the National Cancer Institute and was named the 2009 Top Basic Science Jr. Investigator at the Cleveland Clinic.
Directions:
Matheson Hall is located at 32nd and Market Streets.
|
