Large regions of DNA in the human genome that don’t code for proteins were once called “junk” DNA because they were thought to serve no purpose. But with improvements in genome sequencing technologies, scientists are learning that these non-coding regions actually do serve crucial roles in biology.
Now a molecular biologist at Texas Tech University Health Sciences Center at El Paso is studying the role of non-coding regions in the onset, progression, and metastasis of many different types of cancer.
Shrikanth Gadad was recruited to TTUHSC El Paso with the help of a First-Time Tenure-Track Award from CPRIT in 2017 from The University of Texas Southwestern Medical Center, where he was a postdoctoral researcher. He joined the Department of Molecular and Translational Medicine at the Paul L. Foster School of Medicine.
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Large regions of DNA in the human genome that don’t code for proteins were once called “junk” DNA because they were thought to serve no purpose. But with improvements in genome sequencing technologies, scientists are learning that these non-coding regions actually do serve crucial roles in biology.
Now a molecular biologist at Texas Tech University Health Sciences Center at El Paso is studying the role of non-coding regions in the onset, progression, and metastasis of many different types of cancer.
Shrikanth Gadad was recruited to TTUHSC El Paso with the help of a First-Time Tenure-Track Award from CPRIT in 2017 from The University of Texas Southwestern Medical Center, where he was a postdoctoral researcher. He joined the Department of Molecular and Translational Medicine at the Paul L. Foster School of Medicine.
DNA is transcribed into much shorter lengths of genetic material, called RNAs, that contain the code for making proteins. Gadad’s work is based on the fact that not all RNAs code for proteins, as was previously thought, but themselves serve important regulatory functions inside cells. Gadad is studying a particular type called long non-coding RNAs.
Most of these long non-coding RNAs are very specific to a particular tissue type — ones found in skin cells won’t be found in lung cells, for example. Others are specific to the developmental stage of the organism, for example, present in infancy but not in adulthood. It turns out that long non-coding RNAs in cancer are also very specific to the type and stage of cancer, and can be used as biomarkers for detecting and staging cancer.
Gadad also found RNAs that, although previously thought to be non-coding, actually make small pieces of proteins called peptides. For patients who have breast biopsies, these novel peptides serve as biomarkers to reveal the presence of cancer as well as determine molecular subtypes. The peptides appear to play a role in regulating signaling pathways inside cancer cells.
In cultured breast cancer cells and in mice, Gadad has found that shutting down long non-coding RNA prevents the cancer cells from reproducing. To accomplish this, Gadad introduces a "small interfering RNA" that binds to the RNA in the cancer cells and degrades it, disrupting the cancer cells’ metabolism. His next step is to try this same approach to keep patient-derived tumors from growing in mice.
These long non-coding RNAs are also found in ovarian cancer as well as a type of brain tumor called glioblastoma. Some of these long non-coding RNAs are also expressed in prostate cancer as well.
“If we can develop therapies that specifically target these RNAs and peptides that are only found in cancer cells, there won’t be have any side effects, since they are not found in normal tissues,” Gadad says. “It will help us to combat ever-evolving cancers with minimal side effects.”
Gadad appreciates the support from CPRIT, which has enabled him to hire talented researchers for his laboratory and employ cutting-edge technologies to conduct innovative research to understand and combat cancer.
Gadad received his undergraduate and master’s degrees from the University of Agricultural Sciences in Dharwad, India, and his Ph.D. in molecular biology and genetics from Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India. He came to the U.S. in 2010 as a postdoctoral fellow at Cornell University, studying gene expression in the laboratory of W. Lee Kraus. He followed his advisor to UTSW.
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