(1) Cancer Prevention and Treatment have been the main focus of Dr. Gudas’ and her colleagues research and she and her lab continue to make major strides. They have developed mouse models of various cancers—head and neck and kidney cancer—testing new therapies, including a new immunotherapy for clear cell renal cell carcinoma. Some of the chemicals that they are testing to treat these cancers are various forms of the vitamin Vitamin A (retinol), which is actively being used clinically to successfully treat acute promyelocytic leukemia. Vitamin A enables some undeniably essential functions in the human body: the workings of the immune system, vision, and epithelial cell differentiation, for example. In the 1980s, researchers discovered that vitamin A and one of its metabolites, retinoic acid, could be used to treat certain cancers.
Dr. Gudas and her research team use state of the art molecular pharmacology technologies in their research; research projects in the Gudas lab focus on: (a) understanding the functions of the three retinoic acid receptors (a,b,& g), which are transcription factors, in mediating the actions of vitamin A to prevent/treat head and neck cancer, (b) delineating the functions of another transcription factor, ATF4, which is elevated in clear cell renal cell carcinoma,& (c) testing a new dendritic cell immunotherapy for kidney cancer.
(2) Liver and Kidney Diseases Related to Type 2 Diabetes and Alcohol Use. Recently, to Gudas’ surprise and delight, she and her team made breakthroughs in understanding retinoids’ seemingly critical role in diabetes and related liver and kidney dysfunction. Gudas’ newer area of research began when her lab used retinoic acid to induce the differentiation of embryonic stem cells into pancreatic endocrine cells. These are cells in the pancreas that produce insulin,the cells that often die in patients with diabetes.
If the body needs retinoic acid to make insulin-producing cells, what happens if the body doesn’t have enough retinoic acid? Is diabetes associated with vitamin A deficiency? To test this idea Gudas and her lab put mice on a vitamin A deficient diet. Within 10 weeks, the mice manifested a type of advanced diabetes. “We showed that vitamin A deficiency essentially led to the loss of cells that make insulin in the pancreas,” Gudas says. “No one had ever shown this before. We also then showed that obese, diabetic mice, despite having normal vitamin A levels in their diet and their blood, had very little vitamin A in their tissues, including the liver, lungs, kidneys, and pancreas.” The findings constitute a breakthrough. In addition, Gudas notes, “Fatty liver disease, also known as MAFLD, is on the rise in America and is associated with obesity, so this disease could be associated with vitamin A deficiency in the liver as well.”
Current research projects include: (a) delineating the mechanism(s) by which a drug that binds and activates retinoic acid receptor b can reduce liver and kidney damage and dysfunction associated with either obesity or excessive alcohol use, and (b) developing new treatments for fibrosis associated with obesity and alcohol intake.
Selected Publications: https://pubmed.ncbi.nlm.nih.gov/?term=Gudas+LJ
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