About Our Research

Nearly a century ago, Otto Warburg first observed that tumors are metabolically distinct from normal tissues. Research on cancer metabolism has dramatically expanded in recent years, and as a result our understanding of the unique metabolic properties of tumors has grown. This research has also resulted in the clinical approval of several new metabolic therapies, with many more currently in development. But as is often the case in science, the new discoveries in the cancer metabolism field have raised just as many questions as they have answered, and have revealed how much we still have to learn about the complex metabolic activity of tumor cells.

In the Coloff Lab, we focus on understanding the unique metabolic properties of breast tumors. Breast cancer is one of the two most common types of cancer in the world, and women in the United States have a 1 in 8 lifetime chance of developing breast cancer. The good news is that our investment in cancer research is paying off, as the incidence and fatality rates for breast cancer are declining. Our goal is to continue and accelerate this trend by identifying new treatments for the many patients who have run out of effective therapeutic options.

One of our major current projects is identifying metabolic differences between different subtypes of breast cancer. Building on previous work by our lab and others, we have identified significant differences in serine metabolism between luminal/ER+ and basal/ER- breast tumors. Serine is considered a non-essential amino acid at the organismal level, but it is critically important for many functions in cancer cells. We have found that unlike basal breast cancer cells, luminal/ER+ breast cancer cells are unable to make their own serine and are therefore entirely dependent on acquiring serine from the circulation. Interestingly, this dependency on exogenous serine sensitizes luminal tumors to dietary serine starvation, which is currently being investigated as a potential cancer treatment. Importantly, the inability to synthesize serine seems to be a unique property of luminal breast cancer cells, suggesting that this tumor type may be uniquely sensitive to therapies aimed at reducing serine availability. Currently, we are further investigating serine auxotrophy as a potential therapeutic vulnerability of luminal/ER+ breast tumors by working to better understand how cells respond to serine starvation and by exploring additional approaches of starving cancer cells of serine in vivo.

Our laboratory is also interested in improving the methods by which we study the metabolism of cancer cells. One area that we have contributed to this effort is by developing methods of studying cellular metabolism in three-dimensional tissue culture models. More recently, we have become very interested in efforts to improve the tissue culture medium that is used to grow cancer cells in vitro. These studies have revealed the importance of nutrient availability in controlling the response of breast cancer cells to certain chemotherapies, and we are now investigating potential opportunities to manipulate systemic metabolism to improve the efficacy of a variety of cancer therapies. These studies have the opportunity to improve existing breast cancer therapies, which could lead to rapid benefits for breast cancer patients.

As an offshoot of this work, we have become interested in understanding how cancer cells balance lipid uptake and lipid synthesis. Our work with physiological media led to the realization that traditional culture media is likely a lipid-starved environment that may dramatically skew the balance of lipid synthesis and uptake in cancer cells. To rectify these issues, we are currently studying what lipids are available to cancer cells in tumors. We are then using this knowledge to better recreate in vivo conditions in culture, which we believe will significantly improve our ability to study tumor lipid metabolism in vitro. Given the importance of lipids in many aspects of cell biology, we believe that these studies could have a significant impact on our knowledge of lipid metabolism in cancer.