Klinge Lab

About

My two areas of current research are breast cancer and metabolic dysfunction-associated steatotic liver disease (MASLD).  We are examining the molecular mechanisms of estrogen action and endocrine therapy resistance in breast cancer and liver responses to diet and environmental pollutants that promote MASLD. We reported cell-and tissue-based studies on estrogen receptor-DNA interaction, transcriptional regulation of mRNA and noncoding RNAs, and their gene targets, protein expression, lipidomics, and mechanisms of endocrine disrupting and metabolism disrupting chemicals. We use Oxford Nanopore long read, direct RNA- seq to identify site-specific m6A in mRNA transcripts; Illumina short read RNA- and miRNA-seq, m6A-RNA-immunoprecipitation (MeRIP)- RT-qPCR, mass-spectrometry-based detection of RNA modifications, proteomics, metabolomics, and quantitative bioinformatic data analyses.  We recently performed single nuclear RNA seq (snRNA-seq, Parse Biosciences) to define the transcriptome changes in human breast cancer patient derived xenograft (PDX) grown by Dr. Brian Clem in the mammary milk ducts of female mice, using the mouse intra-ductal (MIND) model.  In collaboration with Dr. Matthew Cave, we are examining how epitranscriptomic changes in mouse liver following exposure to high or low-fat diets in combination with PCB exposures impact m6A epitranscriptome changes, splicing, transcript and protein abundance in genes in lipid metabolism in MASLD.

Key Research Areas

• Breast cancer
• Endocrine-resistance
• Metabolic-associated steatotic liver disease (MASLD)
• Environmental exposures
• Direct RNA-seq
• Epitranscriptomics: m6A in mRNA
• snRNA-seq
• miRNA

Current Projects

• “m6A epitranscriptome drivers of endocrine-resistant breast cancer” funded by a grant from the Office of the Assistant Secretary of Defense for Health Affairs, in the amount of $1,313,309.00, through the Breast Cancer Research Program under Award No. HT9425-23-1-0017: Klinge, C.M., (PI), Clem, B.C. (MPI)
• NIH 1 R01ES036210-01A1 “RNA modifications in apolipoprotein regulation by environmental exposures” Klinge, C.M., (PI), Cave, M.C. (MPI)

Team

Kellianne M. Piell, B.S., Lab Manager, Research Technician; Email: kellianne.piell@louisville.edu 502-852-1640

Belinda J. Petri, Ph.D., Postdoctoral Fellow. Email: belinda.petri@louisville.edu Phone: 502-852-1503

Ahtesham Hussain, Ph.D., Postdoctoral Fellow. Email: ahtesham.hussain@louisville.edu Phone 502-852-1640

Anjali Kumari, M.D., Ph.D. Postdoctoral Fellow. Email: anjali.kumari@louisville.edu Phone 502-852-1640

Gjhvona Bryant, M.S., Graduate student. Email : gjhvona.bryant@louisville.ed Phone 502-852-1640

Abigail Shaw, B.S., abigail.shaw@louisville.edu Graduate Student. Email Phone 502-852-1640

Recent Publications

• Petri, B.J., Piell, K.M, Wahlang, B., Chariker, J.H., Rouchka, E.C., Cave, M.C., and Klinge, C.M.  Long-read isoform sequencing reveals Aroclor1260-induced isoform usage in mouse liver. Genes 17:126 , 2026. Epub 25 Jan 2026 doi:10.3390/genes17020126
• Petri, B.J., Piell, K.M., Avila-Valdes, B.L., Stanley, C.G., Winkler, LJ., Brown, J.T., Ulett, R., Sanchez, G., Chariker, J.H., Rouchka, E.C., and Klinge, C.M. Integrated Nanopore and short-read RNA sequencing identifies dysregulation of METTL3- m6A modifications in endocrine therapy- sensitive and resistant breast cancer cells. Functional & Integrative Genomics 25: 149, 2025 Epub 2025 July 9, doi:10.1007/s10142-025-01658-2  PMID: 40632306
• Klinge, C.M., (corresponding author); Chariker, J.H., Piell, K.M., Petri, B.J., Rouchka E.C., and Cave, M.C. Polychlorinated biphenyl exposure alters tRNA transcriptome in high fat diet-fed mouse liver. Non-coding RNA 11: 41, 2025.   Epub 2025 May 22 doi: 10.3390/ncrna11030041 PMID 40559619  PMCID: PMC12195632
• Piell, K.M., Poulton, C.C., Stanley, C.G., Schultz, D.J., and Klinge, C.M. Integrated Metabolomics and Transcriptomics Analysis of Anacardic Acid Inhibition of Breast Cancer Cell Viability. Int. J. Mol. Sci. 25:7044, 2024 Epub. 2024 June 27   PMID: 39000156  PMCID: PMC11241071 DOI: 10.3390/ijms25137044
• Petri, B.J., Piell, K.M., Xu, J., Cai, L., Rai, S.N., Li, M., Wilkey, D.W., Merchant, M.L., Cave, M.C., and Klinge C.M. Chronic Aroclor 1260 Exposure Alters the Mouse Liver Proteome, Selenoproteins, and Metals in Steatotic Liver Disease. Environ. Toxicol. Pharmacol. 107: 104430, 2024.  Epub. 2024 Mar 27. PMID: 38552755 PMCID: PMC11044900 doi:https://doi.org/10.1016/j.etap.2024.104430
• Petri, B.J., Piell, K.M., Wahlang, B., Head, K.Z., Rouchka, E.C., Park, J.W., Hwang, J.Y., Banerjee, M., Cave, M.C., and Klinge C.M. Altered splicing factor and alternative splicing events in a mouse model of diet- and polychlorinated biphenyl-induced liver disease. Environ. Toxicol. Pharmacol. 103: 104260, 2023. Epub. 2023 September 6.  PMID: 37683712 PMCID: PMC10591945   DOI: 10.1016/j.etap.2023.104260
• Petri, B.J., Cave, M.C., and Klinge, C.M. Changes in m6A in Steatotic Liver Disease.  Genes 14: 1653, 2023. Epub 2023 August 19; doi: 10.3390/genes14081653; PMID: 37628704 PMCID PMC10454815 
• Petri, B.J., Piell, K.M., Wilt, A., Howser, A.D., Winkler, L., Whitworth, M.R., Valdes, B.L., Lehman, N., Clem, B.F., and Klinge C.M. microRNA Regulation of the Serine Synthesis Pathway in Endocrine-resistant Breast Cancer Cells. Endocrine-Related Cancer 30: e230148, 2023. Epub. 2023 August 1. PMID: 37650685 PMCID: PMC10546957  DOI: 10.1530/ERC-23-0148
• Petri, B.J. and Klinge, C.M. m6A Readers, Writers, Erasers, and the m6A Epitranscriptome in Breast Cancer. J. Mol. Endocrinol. 70: e220110, 2023. Epub 2022 November 11; DOI: 10.1530/JME-22-0110; PMID: 36367225 PMCID: PMC9790079