Picture by Victor Anosike
Originally published in The Campus on February 2019
As principal investigators across the country continue to perform research to understand diseases of the cardiovascular system, Dr. Jun Yoshioka, an Associate Professor at the CUNY School of Medicine, is at the forefront of understanding the link between certain genes, their effect on heart function, and their effect on diabetes.
Dr. Yoshioka’s focus is the TXNIP gene and its effects on patients who have diabetes. His research embodies the intersection between research and clinical care, an intersection that is necessary for the advancement of the medical field.
The TXNIP gene, which stands for Thioredoxin-Interacting Protein, is a gene that encodes for an important protein in cells and helps inhibit thioredoxin, an important antioxidant in the body. Although TXNIP and its role in regulating antioxidants was identified in the 1990s, few research teams were actively interested in investigating its potential effects on other mechanisms in the body. This changed around the early 2000s with the introduction of microarrays, tiny devices that allow researchers to quickly determine the expression level of multiple genes at once for different types of cells.
“[Before microarrays], you had to determine gene expression levels one by one. Microarrays were used to see what kind of genes were upregulated, and what kind of genes were downregulated. Eventually, a lot of researchers found TXNIP [as one of the genes they wanted to study].”
During this increased interest for TXNIP research amongst the medical community, Dr. Yoshioka was one of the first to characterize the role of TXNIP and how it affects the function of cardiomyocytes, or muscle cells found in the heart. To do this, Dr. Yoshioka exposed the cardiomyocyte cells to the mechanical stress that was similar to the force heart cells normally experience as they pump blood.
“We generated mechanical stress on the dish, extracted the genetic material, ran the microarray chip, and found that TXNIP was upregulated. We realized that if mechanical force can trigger TXNIP, then it should play an important role in cardiac function.”
But TXNIP wasn’t just upregulated as a result of mechanical force. A substance that is being studied in vast amount of research labs was found to also increase TXNIP expressions, finally causing the gene to graduate from its status of relative obscurity in the 1990s to prime importance in the medical research community in the current era - sugar.
Glucose, a sugar that serves as a major source of energy for the body, is a key component of metabolism, the biochemical processes that allow organisms to live and function.
“Our group was one of the first to find that adding glucose upregulates TXNIP really high…Glucose [is related to] metabolism, and everyone is interested in metabolism. Oncologists are interested in metabolism because cancer cells have a different metabolism from normal cells. Neurologists are interested in metabolism because glucose metabolism is the major energy source in the brain; All different types of researchers jumped into the TXNIP world. That is why the publication number about TXNIP exponentially increased in the last decade. I believe the gene is very important in many different human diseases.”
Currently, two of the diseases that Dr. Yoshioka believes are connected to TXNIP are diabetes and cancer. TXNIP acts as a tumor suppressor gene, which means that it participates in the destruction of cells that are considered to be cancerous. Although having high TXNIP levels are ideal for patients with cancer, low levels of the gene would be more suitable for people without cancer, since the high levels of the gene can kill normal cells as well. However, patients with diabetes (and thus large amounts of glucose in their blood stream) would express large amounts of TXNIP, since glucose has been proven to increase TXNIP levels. This can cause diabetic patients to have damaged cells in multiple organs in their body, including the kidney, pancreas, and liver. The key dilemma involves finding a way to use high TXNIP in cancer patients and low TXNIP in diabetic patients. “Eventually I hope that TXNIP is a target for diabetic and cancer therapy.”
Although Dr. Yoshioka began his career as a medical doctor, he has chosen to devote most of his time to medical research. Oftentimes, medical professionals with interests in both the clinical and research aspects of medicine have to choose between managing their time dealing with the hands on demands of clinical work and dealing with the competitiveness and oversight required to conduct funded medical research. Dr. Yoshioka believes that every physician will eventually find their own balance.
“Since I was a medical student, I always wanted to do three things. One is clinical work, the other is research, and the third one is teaching. I was happy to start working with people in the clinical portion. At the same time, you have to deal with the fact that your patients still die. I also noticed that a lot of clinicians around myself- and I mean no offense- did not understand pathophysiology in depth. They just followed the guidelines for a specific condition, such as a heart attack. Of course I cannot cure a heart attack, but I wanted to understand more of the disease and find something new. That is what I was always thinking when I was a resident. That is why I went to grad school.”
Based on the amount of success Dr. Yoshioka has had in terms of clearing the path for TXNIP research in the scientific world, leaning towards one aspect of the medical field has its advantages for those who have the passion and drive.
“As one of the initial researchers who studied TXNIP biology, I generated the antibodies and the animal models.” Antibodies, specialized proteins found in your immune system that are designed to attach to specific proteins or compounds, are a key component of medical research. “I generated the antibodies, and the [antibody’s initials] are JY, my initials. If you type in ‘TXNIP antibody JY,’ you will see that the antibodies I created are the standard for TXNIP studying. More than half the papers out there use my antibodies, so indirectly I contribute to cancer research, but I do not have a direct collaborator for cancer.”
Aside from conducting research, Dr. Yoshioka also teaches at Sophie Davis. His biggest advice for those looking to do medicine (research or clinical) is to expose yourself by offering to work in a lab. “Try to expose yourself in a basic research environment when you are still young, even if your goal is to become a clinical physician…if you experience the real world in a lab, it is easier to see the lab results as a physician.”
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