Taniguchi Laboratory

Our lab studies the biology of hypoxia (or low oxygen levels in tissues) and how it affects the growth and function of tumor and our normal tissues. Although you might think that low oxygen levels are not a normal stimulus for our cells, it is actually quite routine for most tissue to experience periods of low oxygen. In periods when oxygen levels drop, our cells need to be able to activate a powerful adaptive response in order to survive. For instance, when you get a paper cut (ouch!), you get a small wound that bleeds. Since you have cut through some blood vessels, and blood delivers oxygen, the edges of the wound are often in a state of low oxygen, called hypoxia. This hypoxic state stimulates a powerful healing response that helps you seal the wound. In fact, other researchers have found that activating this hypoxic response prior to ischemia (sudden loss of oxygen in any tissue, such as with heart attacks or stroke) actually protects cells from death.

The mechanisms controlling hypoxic-stimulation of healing in tissues is complex. It drastically alters the growth and metabolism of cells and primes the them to depend less on oxygen.

Unfortunately, this same biology may also help tumors to thrive. When a tumor gets large enough, it can alter the blood flow to a region of the body and render it hypoxic. This low oxygen environment is interpreted by other nearby normal cells to form a cellular complex called stroma, which may help to form a favorable microenvironment that promotes tumor growth. The complex interplay of the hypoxia pathway within the tumor, stroma and normal tissues is crucial in determining the various aspects of clinical outcomes of a tumor, such as metastasis, drug resistance and response to chemotherapy and radiation therapy. There is probably no cancer with a more substantive stroma than pancreatic cancer (Erkan et.al., 2012).

We're trying to exploit these techniques to reduce toxicity from cancer treatments. In addition, we can further enhance tumor killing using a technique called Stereotactic Body Radiotherapy (SBRT), which uses advanced image guidance to precisely deliver high doses of radiation to the tumor, but not nearby normal tissues. By combining these two approaches we believe that we can deliver a therapeutic, and potentially curative, dose of radiation to tumors of the pancreas and liver.

Our lab has several translational projects that aim to understand and harness hypoxia biology to our advantage in treating pancreatic cancer. We use model pancreatic cancer both with genetically engineered preclinical models and tumor organoids obtained directly from patients at MD Anderson.