Food for Cells
Dermatologist and physician-scientist Stefan Schieke, MD, is “fascinated by how our everyday choices, like what we eat and drink, affect cancer development and growth, and even how we treat it.”
Dr. Schieke’s current research examines the role of the mitochondria—the powerhouses of the cell—in determining the behavior of other parts of the cell. How do different nutrients consumed by the mitochondria affect other aspects of the cell, and are certain nutrients fueling more aggressive lymphocytic cancer cells in patients?
Your Mitochondria’s Menu
Research on metabolism has been done for decades in isolated cells growing in culture, laying the foundation for our current understanding of the complicated network of metabolic pathways inside cells. More recent work, however, in both animals and humans, has shown that nutrient choices and the metabolic activity of cells in living organisms can be vastly different from those observed in the same cells in culture conditions.
Cells in a petri dish have access to a virtually limitless supply and variety of nutrients, but cells in the human body have a much more limited menu of nutrients to choose from, based on whatever we’ve eaten lately and which nutrients have made it from our plates into the tissue microenvironment surrounding the cell.
That is, the choices we make when eating, along with other factors (such as how our digestive tract functions), dictate which nutrients are available for mitochondria to metabolize and pass along to other parts of the cell. Therefore, to understand how a cancer cell’s metabolism and fuel choices fit into the metabolic activity of the whole organism, Dr. Schieke studies this question in patients rather than relying exclusively on isolated cells in culture.
This question of which nutrients are available to cells in a living being, and which ones the mitochondria choose to metabolize, is what Schieke is currently studying in patients with leukemia. “While we have known for a very long time that your diet affects your body and health, we are only beginning to appreciate that the same is true for the cells and their choice of fuel within our body.”
Parts of this work will be supported by the UW2020 grant “Metabolic profiling of leukemic cells through isotope tracing in patients with chronic lymphocytic leukemia” recently awarded to the Schieke lab together with Drs. Jing Fan and Christopher Fletcher.
Putting Cancer On a Diet
This line of inquiry has practical implications. In groundbreaking research published last December, Schieke discovered how the well-known diabetes drug Metformin, and the related compound Phenformin, can be used to treat incurable lymphoid cancers like leukemia, acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Dr. Schieke studied the effect of the drugs on cancer cells’ mitochondria.
Schieke discovered that cancer cells treated with Metformin adapt by switching to a strict diet of glucose, and also identified the cellular process that allows this adaptation. Another known class of drugs, called HIF-1α inhibitors, can prevent the dietary adaptation to glucose. Schieke proposed that by treating cells with Metformin and a HIF-1α inhibitor, the cancerous cells would be unable to eat, and die. What’s more, this combination of drugs targets only cancer cells, leaving healthy cells untouched!
Laboratory studies by Schieke and his team confirmed the hypothesis. The study and Schieke’s proposed treatment are already being developed for clinical research at the UW Carbone Cancer Center.
Active Clinical Trials
Dr. Schieke on…
Being a physician-scientist
In science we are used to asking questions we do not know the answer to. If we knew the answer, we wouldn’t study it. But in medicine, the assumption is that if someone asks a question—about their health, their body, their cancer—we should be able to come up with an answer.
This can sometimes make us afraid as doctors to ask the unanswerable questions. Why does a drug work? Why do things happen the way they happen? A lot of the scientific questions we ask in the lab are informed by seeing these things in clinic that we cannot explain. Being in both positions provides a unique perspective on the conditions and their complexity.
His Favorite Medical School Memory
It’s a completely nerdy answer–my biochemistry class! Also the parties after our exams ended were really fun! It was over 20 years ago!
His Favorite place in Wisconsin
Wisconsin is such a beautiful state with 4 distinct seasons! I always look forward to having ice cream at the terrace during the summertime and family hikes to Devil’s Lake. I am also an avid cyclist, so anytime I get to spend outdoors I cherish.
UW Health West Clinic (451 Junction Rd.)
Middleton VA Hospital