Bajpai, an assistant professor in the School of Sustainable Chemical, Biological and Materials Engineering, will lead the project, “Epigenetic and Transcriptional Mechanisms Driving Human Pigmentation Diversity.”
Using the gene-editing technology CRISPR, Bajpai led a recent discovery of 135 new melanin genes associated with human pigmentation.
“We discovered new factors (genes) which are present in our DNA that make us unique in terms of color and creates diversity among the human population,” Bajpai said. “But now the bigger questions are which of these genes are most important? How do changes in these genes cause pigmentation diseases, including melanoma, and can we exploit the power of these genes to engineer therapies against diseases? Our lab is utilizing cutting-edge technologies, diverse model systems and engineering principles to propel this project, which has both fundamental and applied directions.”
For this project, Bajpai’s research group will explore what controls the genes that make up pigment melanin in the skin – currently an open question in the field. He is trying to understand how these genes relate to one another and other genes in the body to determine if there are “critical nodes” that may be important for driving major shifts in the process of melanin synthesis that results in pigmentation.
“We found a class of genes called transcription factors,” he said. “These are the proteins which bind to the DNA, then they affect the production of many other proteins in the cells. In terms of gene functioning, some of the genes could be in a hierarchy and regulating a bunch of other genes, and we are further investigating this.”
Another aspect is the clinical and translational application of his project. Some market estimates cite the global market of pigmentation disorders treatments is $7 billion annually and is projected to reach $9.2 billion by 2028.
“Clearly, there is an unmet need,” Bajpai said. He envisions manipulating these genes’ actions in patients’ skin to obtain the desired pigmentation levels in patients who are suffering from hyper or hypopigmentation diseases.
This award will also allow his research group to investigate the link between lighter skin color and melanoma susceptibility. According to the Centers for Disease Control and Prevention, about 6 million people each year in the United States are treated for skin cancer of any kind, but of those, melanoma causes the most deaths among all types of skin cancer, and incidence rates have increased over time. Findings from a 2016 National Institutes of Health report showed overall melanoma mortality was higher in white non-Hispanics in Oklahoma than the national average.
Many of the 135 melanin genes Bajpai discovered are present at different levels in light- and dark-skinned humans. He believes their variable levels in skin cells contribute toward melanoma initiation. “By having a finer understanding of how these genes work in melanoma and manipulating their levels, we intend to engineer therapeutic strategies,” he said.