The laboratory utilizes novel skin fold window chambers in rats and mice to study tumor blood flow and oxygen transport (see Figure 1). Disorganized vascular supply, poor oxygenation and lowered pH are pathophysiological hallmarks of tumors. These features of tumor physiology contribute directly to resistance to treatment. Altered gene expression also contributes to treatment resistance as well as selection for more malignant phenotypes. Genes that are involved include many cytokines involved in regulation of angiogenesis, protection from oxidative stress and cell cycle control.

Studies of oxygen transport emphasize determination of causes for poor oxygen and other nutrient delivery to tumors. It is known that there are two relatively independent causes for hypoxia in tumors. These features of discordant transport are commonly referred to as chronic and acute hypoxia. Chronic hypoxia develops as a consequence of abnormally low vascular density, combined with relatively few sources of arterial supply and oxygen consumption rates that are out of balance with supply. Recently, we have discovered that the limited arterial supply to tumors contributes to steep gradients in pO2, such that the vessels supplying tumor at the most distant site from the feeding arterioles are also hypoxic (see Figure 2). We refer to these sites as "hypoxic corners", which we believe will present the greatest challenge for strategies to improve oxygenation. Two important recent discoveries relate to blood flow and oxygenation instability and investigates methods to improve oxygenation, since this Abnormal microvasculature and elevated oxygen consumption rates undoubtedly contribute to varying levels of hypoxia and nutrient deprivation in most, if not all solid cancers. The resultant sub-optimal microenvironment contributes directly to resistance to radiation and chemotherapy. In addition, altered gene function, resulting from the abnormal microenvironment could indirectly contribute to altered biologic behavior, such as enhanced rates of metastasis and increased invasiveness. A new area of emphasis for the laboratory is to identify new genes whose function is altered in this type of environment.