Congratulations to our CTSI Research Pilot Award Recipients!
PI: Kristanna Fredenburg, M.D., Ph.D.
Title: Investigating the Functional Role of Differentially Expressed microRNAs from Black compared with White Laryngeal Cancers
Mentor: Tom Schmittgen, PhD- Department of Pharmaceutics.
Abstract: The burden of head and neck cancer is greater for Blacks than Whites and expressly so for laryngeal squamous cell carcinoma (LSCC). For several decades, Blacks have maintained a higher incidence, prevalence, and lower survival rates compared with any other race. Moreover, among all cancers, the death rate for LSCC is one of the highest in Black males compared with White males. Epidemiologic factors certainly play a role; however, after controlling for these factors, the disparity remains. This suggests a heritable contribution but to date it remains undefined. Although microRNAs (miRNAs) have been found to be dysregulated in LSCC, no studies have investigated the differential regulation of miRNAs between Black and Whites. We present, here, our small RNA sequencing and qPCR validation data on two miRNAs, miR-9-5p and miR-191-5p. Our data show that the somatic expression of miR-9-5p and miR-191-5p differs significantly between Black LSCC and White LSCCs. Since miR-9-5p and miR-191-5p have been identified as cancer-related miRNAs, we hypothesize that differential expression of these miRNAs and the functional consequences play a role in racially disparate outcomes seen in LSCC. Discovering the functional impact of these miRNAs in LSCC may provide additional insights into the racial disparity.
PI: Iqbal Mahmud, Ph.D.
Title: Multi-omics approach to elucidate the metabolome alteration in children with malnutrition in the development of clinical intervention
Mentor: Timothy Garrett, Ph.D.
Abstract: Malnutrition is the major global public health problem in the world. It is attributed to a myriad of factors, including poor prenatal nutrition, poverty and food insecurity, nutrient deficiencies, inadequate child feeding practices, poor hygiene, and infectious diseases. Malnutrition causes the death of 3.5 million children per year under five years old. These serious public health issues lead to a higher chance of living in poverty in adulthood and consequently reduced economic productivity and increases the serious national burden. Currently, most of the finding on malnutrition has been from epidemiological studies and approaches based on this data result in exceedingly poor outcomes among supplemented malnourished children. Molecular mechanisms associated with malnutrition are limited. We plan to use Multi-omics approach to elucidate the metabolome alteration in children with malnutrition in the development of precision therapeutics. The project can lead to a better understanding of the underlying pathophysiology of malnutrition (undernutrition and overnutrition).
PI: Naohiro Terada, M.D., Ph.D.
Title: A Drug Discovery Platform for X-Linked Disorders Using Female iPSCs
Co-Is: Christy Pacak, Pediatrics & Jim Resnick, MMG
Abstract: There are many X-linked recessive disorders usually manifesting only in boys, such as red-green color blindness, hemophilia and Duchenne muscular dystrophy. Here we propose a novel drug screening platform by making iPSCs from their carrier mothers, as they may become more useful tools for drug discovery. Having proper controls, here served by isogenic cells expressing the counterpart normal X chromosome, are essential when screening effective chemicals. Similarly, in X-linked dominant disorders, such as fragile X syndrome and Rett syndrome, iPSCs from female patients themselves would provide a perfect set of disease and control cells in an isogenic manner. The drug screening systems we develop here, as proof of concepts for both X-linked recessive and dominant disorders, provide a powerful tool to find a cure on such diseases.