Bio


Ph.D., AFPE Pre-doctoral Fellow, Pharmaceutical Sciences, The University of Texas at Austin
Fulbright U.S. Postdoctoral Scholar, Biomedical Research Institute of Malaga, Spain

Academic Appointments


All Publications


  • Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots. Nature communications Kompella, P., Wang, G., Durrett, R. E., Lai, Y., Marin, C., Liu, Y., Habib, S. L., DiGiovanni, J., Vasquez, K. M. 2024; 15 (1): 6213

    Abstract

    Obesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.

    View details for DOI 10.1038/s41467-024-50006-8

    View details for PubMedID 39043652

    View details for PubMedCentralID 4859313

  • 8-Oxoguanine DNA Glycosylase 1 Upregulation as a Risk Factor for Obesity and Colorectal Cancer. International journal of molecular sciences Pilo, J., García-Flores, L. A., Clemente-Postigo, M., Arranz-Salas, I., Alcaide, J., Ramos-Fernandez, M., Lozano, J., Boughanem, H., Kompella, P., Macías-González, M. 2023; 24 (6)

    Abstract

    DNA damage has been extensively studied as a potentially helpful tool in assessing and preventing cancer, having been widely associated with the deregulation of DNA damage repair (DDR) genes and with an increased risk of cancer. Adipose tissue and tumoral cells engage in a reciprocal interaction to establish an inflammatory microenvironment that enhances cancer growth by modifying epigenetic and gene expression patterns. Here, we hypothesize that 8-oxoguanine DNA glycosylase 1 (OGG1)-a DNA repair enzyme-may represent an attractive target that connects colorectal cancer (CRC) and obesity. In order to understand the mechanisms underlying the development of CRC and obesity, the expression and methylation of DDR genes were analyzed in visceral adipose tissue from CRC and healthy participants. Gene expression analysis revealed an upregulation of OGG1 expression in CRC participants (p < 0.005) and a downregulation of OGG1 in normal-weight healthy patients (p < 0.05). Interestingly, the methylation analysis showed the hypermethylation of OGG1 in CRC patients (p < 0.05). Moreover, expression patterns of OGG1 were found to be regulated by vitamin D and inflammatory genes. In general, our results showed evidence that OGG1 can regulate CRC risk through obesity and may act as a biomarker for CRC.

    View details for DOI 10.3390/ijms24065488

    View details for PubMedID 36982562

    View details for PubMedCentralID PMC10052644

  • An overview of vitamins as epidrugs for colorectal cancer prevention. Nutrition reviews Boughanem, H., Kompella, P., Tinahones, F. J., Macias-Gonzalez, M. 2023; 81 (4): 455-479

    Abstract

    Gene expression altering epigenomic modifications such as DNA methylation, histone modification, and chromosome remodeling is crucial to regulating many biological processes. Several lifestyle factors, such as diet and natural, bioactive food compounds, such as vitamins, modify epigenetic patterns. However, epigenetic dysregulation can increase the risk of many diseases, including cancer. Various studies have provided supporting and contrasting evidence on the relationship between vitamins and cancer risk. Though there is a gap in knowledge about whether dietary vitamins can induce epigenetic modifications in the context of colorectal cancer (CRC), the possibility of using them as epidrugs for CRC treatment is being explored. This is promising because such studies might be informative about the most effective way to use vitamins in combination with DNA methyltransferase inhibitors and other approved therapies to prevent and treat CRC. This review summarizes the available epidemiological and observational studies involving dietary, circulating levels, and supplementation of vitamins and their relationship with CRC risk. Additionally, using available in vitro, in vivo, and human observational studies, the role of vitamins as potential epigenetic modifiers in CRC is discussed. This review is focused on the action of vitamins as modifiers of DNA methylation because aberrant DNA methylation, together with genetic alterations, can induce the initiation and progression of CRC. Although this review presents some studies with promising results, studies with better study designs are necessary. A thorough understanding of the underlying molecular mechanisms of vitamin-mediated epigenetic regulation of CRC genes can help identify effective therapeutic targets for CRC prevention and treatment.

    View details for DOI 10.1093/nutrit/nuac065

    View details for PubMedID 36018754

  • Interactive youth science workshops benefit student participants and graduate student mentors. PLoS biology Kompella, P., Gracia, B., LeBlanc, L., Engelman, S., Kulkarni, C., Desai, N., June, V., March, S., Pattengale, S., Rodriguez-Rivera, G., Ryu, S. W., Strohkendl, I., Mandke, P., Clark, G. 2020; 18 (3): e3000668

    Abstract

    Science communication and outreach are essential for training the next generation of scientists and raising public awareness for science. Providing effective science, technology, engineering, and mathematics (STEM) educational outreach to students in classrooms is challenging because of the need to form partnerships with teachers, the time commitment required for the presenting scientist, and the limited class time allotted for presentations. In our Present Your Ph.D. Thesis to a 12-Year Old outreach project, our novel solution to this problem is hosting a youth science workshop (YSW) on our university campus. The YSW is an interpersonal science communication and outreach experience in which graduate students from diverse scientific disciplines introduce middle and high school students to their cutting-edge research and mentor them to develop a white-board presentation to communicate the research to the workshop audience. Our assessment of the YSW indicated that participating young students expressed significantly more positive attitudes toward science and increased motivation to work in a STEM career after attending the workshop. Qualitative follow-up interviews with participating graduate students' show that even with minimal time commitment, an impactful science communication training experience can be achieved. The YSW is a low-cost, high-reward educational outreach event amenable to all disciplines of science. It enhances interest and support of basic science research while providing opportunities for graduate students to engage with the public, improve their science communication skills, and enhance public understanding of science. This YSW model can be easily implemented at other higher education institutions to globally enhance science outreach initiatives.

    View details for DOI 10.1371/journal.pbio.3000668

    View details for PubMedID 32226010

    View details for PubMedCentralID PMC7145268

  • Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability. Molecular carcinogenesis Kompella, P., Vasquez, K. M. 2019; 58 (9): 1531-1550

    Abstract

    Obesity, defined as a state of positive energy balance with a body mass index exceeding 30 kg/m2 in adults and 95th percentile in children, is an increasing global concern. Approximately one-third of the world's population is overweight or obese, and in the United States alone, obesity affects one in six children. Meta-analysis studies suggest that obesity increases the likelihood of developing several types of cancer, and with poorer outcomes, especially in children. The contribution of obesity to cancer risk requires a better understanding of the association between obesity-induced metabolic changes and its impact on genomic instability, which is a major driving force of tumorigenesis. In this review, we discuss how molecular changes during adipose tissue dysregulation can result in oxidative stress and subsequent DNA damage. This represents one of the many critical steps connecting obesity and cancer since oxidative DNA lesions can result in cancer-associated genetic instability. In addition, the by-products of the oxidative degradation of lipids (e.g., malondialdehyde, 4-hydroxynonenal, and acrolein), and gut microbiota-mediated secondary bile acid metabolites (e.g., deoxycholic acid and lithocholic acid), can function as genotoxic agents and tumor promoters. We also discuss how obesity can impact DNA repair efficiency, potentially contributing to cancer initiation and progression. Finally, we outline obesity-related epigenetic changes and identify the gaps in knowledge to be addressed for the development of better therapeutic strategies for the prevention and treatment of obesity-related cancers.

    View details for DOI 10.1002/mc.23048

    View details for PubMedID 31168912

    View details for PubMedCentralID PMC6692207