- Elucidating pathological mechanisms
- Understanding the diversity of cells derived from a single tumor clone
- Establishing new methods to observe pathological specimens
- Developing objective pathological diagnosis
Observation, analysis and control of tumors exhibiting diverse morphology and function
Pathological diagnosis is important for determining an appropriate treatment strategy for diseases such as cancer. However, accurate diagnosis requires a highly skilled pathologist, and even then opinions can vary. Thus, the lab is interested in the development of accurate biomarkers, which are particularly important for objective pathological diagnosis.
During pathological diagnosis, tissues and cells collected from the affected area are observed to determine the disease, but tumor morphology and function are diverse. A mixture of round and elongated cells occurs frequently, and the expression of cell markers in similarly shaped tumor cells often has completely different characteristics. For example, when examining aldehyde dehydrogenase expression in cells resistant to cancer drugs by immunostaining, morphologically similar tumor cells can be clearly divided into aldehyde dehydrogenase positive and negative populations. In addition the expression of amino acid metabolizing enzymes, even in the same tumor, is drastically reduced in the most invasive region (Figure 1). The lab revealed that this is because the expression of DEPTOR protein, which negatively regulates the signal via mTORC1, is controlled by amino acid metabolizing enzymes.
It is unclear whether a tumor is a single clone. Using bone marrow transplantation models, the lab has developed a method to analyze the origins of tumors in combination with in situ hybridization and immunostaining (Figure 2). Furthermore, in contrast to observing pathological specimens by conventional staining of sections and examining them in two dimensions, the lab is experimenting with new methods for observation. By using these methods to directly observe the lesion for tumor cell diversity, pathophysiological mechanisms may be elucidated.