Our Research
We love the smell of Trizol in the morning
LncRNAs and Radiation in Lung Cancers
Worldwide, lung cancer is the leading cause of death by cancer in both men and women. Even though the average overall 5-year survival rate is about 17.8%, women have an overall survival rate two times greater than men. Dysregulation of long non-coding RNAs (lncRNAs) has been shown to contribute to cancer formation and resistance to chemotherapy and radiation therapy.
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Our lab discovered a lncRNAs highly expressed in Non-Small Cell Lung Cancer (NSCLC) cells after radiation treatment. Interestingly, this lncRNA is only present in male cells because it is expressed from the long arm of the Y chromosome. We named this lncRNA: Radiation Induced Y-chromosome linked long non-coding RNA (lnc-RAINY). This lncRNA (previously known as linc-SPRY3 RNAs) gives radiation sensitivity to NSCLC cells by inducing senescence. In addition, the administration of Lnc-RAINY encapsulated in FDA-approved nanoparticles into a lung cancer patient-derived xenograft (PDX) animal model, dramatically reduces tumor progression demonstrating therapeutic potential.
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We are currently investigating the molecular mechanisms that lnc-RAINY uses to regulate several genes involved in radiation resistance as well as developing better gene therapy strategies to improve patient outcomes suffering from lung cancer.
Non-coding RNAs in HPV-Related Cancers
Human Papillomaviruses (HPVs) are small, circular double-stranded DNA viruses, some of which are sexually transmitted. There are more than 200 HPV types divided into low-risk HPVs (associated with the development of genital and oral warts), and high-risk HPVs (involved in the development of anogenital cancers, such as cervical cancer and oral cancers).
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MicroRNAs (miRNAs) are small non-coding RNAs that regulate around 60% of protein coding genes. MiRNAs act as negative regulators of gene expression and changes in miRNA expression have been shown to be associated with most human cancers (The 2024 Nobel Prize in Medicine was given to Dr. Victor Ambros and Dr. Gary Ruvkun for the discovery of miRNAs!). Dr. Martinez has been one of the pioneers studying non-coding RNAs in HPV-related cancers. He published the first study showing that a specific miRNA known as miR-218 is repressed by high-risk HPV type 16 (HPV-16) oncogenic protein E6 in cervical cancer cells. Repression of miR-218 by HPV increases the expression of laminin subunit beta 3 (LAMB3) gene, a subunit of an important receptor that HPV uses to infect epithelial cells (Martinez I, et al. 2008 Oncogene).
Long noncoding RNAs (lncRNA) are a class of ncRNAs that are longer than 200 nucleotides that are not translated into proteins. They regulate a wide variety of cellular processes through diverse mechanisms, including interacting with DNA, RNA, and proteins. The Martinez lab published how a lncRNA known as FAM83H-AS1 is upregulated by HPV-16 E6 viral protein inducing cell migration in cervical and head and neck squamous cell carcinomas (HNSCC) and reducing overall survival in patients with cervical cancer (Barr JA, et al. 2019 Scientific Reports).​
Our current research involves a different type of non-coding RNA known as circular RNAs (circRNAs). CircRNAs are single-stranded, closed loop, non-coding RNAs with specific cellular functions. Most circRNAs originate from back splicing of pre-messenger RNAs (mRNAs) known as canonical circRNAs, and also can be formed from lariat-derived introns, sub-exonic circRNAs, intron circles, etc. (non-canonical circRNAs). Our group is studying the importance of circRNAs in HPV-related cancers.​ We are also studying the newly discovered glycoRNAs and their importance in HPV-related cancers.
MicroRNAs Biogenesis in SARS-CoV-2 Infections
The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has impacted millions of individuals worldwide and is directly responsible for more than one million deaths in the United States alone. In addition, five of the seven known human coronaviruses have been discovered in the last two decades, suggesting that a better understanding of the pathogenic mechanisms of coronaviruses at the molecular level is needed not only for the SARS-CoV-2 pandemic, but for future viral pandemics. MicroRNAs play a major role in the regulation of host and viral genes, including antiviral pathways. We discovered that the microRNA-processing enzyme Drosha, also known as a non-canonical interferon-independent antiviral protein, is cleaved to a smaller isoform after SARS-CoV-2 infection. This shift modified Drosha’s cellular localization. Together, these observations not only elucidate a novel aspect of Drosha’s antiviral role but also advance our understanding of SARS-CoV-2 host–pathogen interactions.
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