Justin Lathia, PhD
Vice Chair and Staff
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-7475
Our two main areas of interest involve using in vivo imaging models to interrogate the tumor microenvironment and examining communication mechanisms used by cancer stem cell to promote their maintenance. Currently our work is focused on malignant brain tumors but our technology and interests are applicable to many other tumor types.
In vivo imaging
To achieve this goal, we rely mainly on in vivo two photon laser scanning microscopy. We have models in which we transplant labeled human brain tumor cells and can watch tumor development in real time. We can also evaluate tumor cell behavior in slice cultures, which allows us to evaluate the molecular contribution of the microenvironment and more appropriately model the human tumor microenvironment. We are in the process of adapting a currently used brain tumor model to be more amendable to in vivo imaging. We also have active collaborations imaging neuroinflammatory processes.
Cells are driven by two main cues an intrinsic and extrinsic program. Within the extrinsic programs, we are interested in how tumor cells interact with one another and the specialized extracellular matrix present in the tumor microenvironment. These interactions drive stem cell maintenance and may represent a new therapeutic angle for tumors.
Cancer is a disease defined by complexity and it has recently been appreciated that many lethal tumors contain a high degree of cellular heterogeneity. Moreover, tumor cells are organized in a cellular hierarchy, with a cancer stem cell at the apex. Cancer stem cells have been characterized in a variety of cancers, including malignant brain tumors, and have been shown to be responsible for tumor formation and therapeutic resistance. Our main interest is how cancer stem cells from malignant brain tumors interact with their surrounding microenvironment, which provides signals to preserve the malignancy of these cells. Specifically, we are interested in cell to cell communication mechanisms as these will help better define the biology of this population and may serve as potent therapies. To fully appreciate cancer stem cell interactions in the appropriate microenvironment, we are developing imaging models to study the communication in real time.
1. Lathia JD, Gallagher J, Myers JT, Vasanji A, McLendon RE, Hjelmeland AB, Huang AY, Rich JN, Direct in vivo evidence for tumor propagation by cancer stem cells, PLoS One 2011, Sept 22
2. Lathia JD, Heddleston JM, Venere M, Rich JN, Deadly teamwork: neural cancer stem cells and the tumor microenvironment, Cell Stem Cell 2011, 8(5):482-85
3. Lathia JD, Gallagher J, Heddleston JM, Wang J, Eyler CE, MacSwords J, Wu Q, Vasanji A, McLendon RE, Hjelmeland AB, Rich JN, Integrin alpha 6 regulates brain tumor stem cells, Cell Stem Cell 2010, 6(5):421-32
Drs. Lathia, Silver and Hine report that a high-fat diet causes hydrogen sulfide dysfunction and leads to more severe disease with poorer outcomes among preclinical glioblastoma models.
This new award will fund a research consortium led by Lerner Research Institute and Case Western Reserve University to study differences in glioblastoma between males and females.
Non-Cancer Cells and Sex Differences in Glioblastoma: The Latest on the Tumor Microenvironment’s Role in Disease
Dr. Lathia found that in female disease models, a protein commonly expressed in glioblastoma tumor cells, called JAM-A, suppresses microglial activity and drives disease metastasis differently than in males.
Dr. Lathia found that the subpopulations of myeloid-derived suppressor cells differ significantly between males and females with the aggressive brain cancer, and that they each contribute to disease pathology differently.
From Bench to Bedside: Low-Dose Chemotherapy Reduces Myeloid-Derived Suppressor Cells in Glioblastoma
In a great story of research translation at Cleveland Clinic, basic research findings from Dr. Lathia’s lab—which elucidated the mechanistic role elevated levels of a certain type of immune cell plays in glioblastoma development—have reached early-stage clinical trial.