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Dr. Jon Huibregtse has been an associate professor of Molecular Genetics and Microbiology at UT since the fall of 2000. He teaches tumor biology and his research focuses on the study of Human Papillomaviruses (HPVs) and their association with uterine cancer, the second leading cause of cancer-related deaths among women worldwide, as well as the biochemistry of the ubiquitin proteolysis system. “Since it is one of the few human cancers where a clear causative link between a virus and cancer has been established, it has allowed us to identify important pathways in the control of cancer by determining the functions of the viral proteins,” he said. Huibregtse’s tumor biology class deals with everything from the pathology of cancer and cancer treatment to the specific molecular defects in cancer cells, and also delves into the historical context of important discoveries to give students a better idea of how we have gotten to the current point of our understanding of cancer. “We discuss how our ideas about mechanisms and causes of cancer have changed over the years,” he said. “For seniors, I think it is a good summation of their undergraduate education in biology, given all the topics we cover.” Huibregtse also makes sure to educate students about being aware of how their behavior influences their risk for cancer. A vaccine for HPV was recently approved and “it’s a very important advance that will impact cancer rates not only in this country, where cervical cancer are already preventable due to relatively good access to heath care, but particularly in developing countries where the majority of deaths due to cervical cancer occur.” The discovery of the mechanism of the HPV E6 protein, a viral protein that targets the p53 tumor suppressor protein, a central player in cancer biology, led to insights into the ubiquitin proteolysis system. This is a pathway for degradation of proteins in eukaryotic cells. E6 essentially hijacks one specific component of this system, called E6AP, which is critical for p53 destruction. “By figuring out how this happens and what enzymes are responsible for this, we discovered a new class of enzymes that play a broad role in determining which proteins in the cell should be degraded,” he said. This new class of enzymes is a group of ubiquitin ligases, know known as HECT E3s. Current lab projects focus on understanding the biochemical mechanism and regulation of HECT E3s, in both mammalian and yeast cells, as well as the continued study of the HPV E6 oncoprotein in carcinogenesis. Another area of study is work that started as a collaboration with Dr. Robert Krug’s lab. Huibregtse and Krug are investigating the ISG15 protein, which is a protein related to ubiquitin that plays a role in the innate immune response to bacterial and viral infections, including influenza viruses. Huibregtse and coworkers discovered that a specific HECT E3 is critical for conjugating ISG15 to cellular proteins. Huibregtse recently spoke about this work at a meeting in Vermont on the biological functions of ubiquitin proteins. He had been the graduate advisor for the Microbiology graduate program for two years and will be one of two graduate advisors for the Cell and Molecular Biology graduate program beginning in the fall. |
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