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A photo of Leah Kottyan.

Assistant Professor, UC Department of Pediatrics

513-636-1316

My Biography & Research

Biography

I am a researcher in the Department of Eosinophilic Disorders and the Center for Autoimmune Genomics and Etiology, where my laboratory studies the genetic etiology of diseases that have an immunological component. I came to Cincinnati Children’s in 2005.

I’m particularly interested in the way genetic variants increase the risk for eosinophilic esophagitis, systemic lupus erythematosus, atopic dermatitis and multiple sclerosis. Because many of the genetic risk variants do not change the protein amino acid code, a lot of our research is focused on genotype-dependent transcriptional regulation in disease-relevant cells and tissues.

I became interested in these areas after leading many genetic studies aimed at identifying polymorphisms in the genome that increase disease risk. As an immunologist and molecular biologist, I want to understand what molecular mechanisms mediate a change in DNA sequence that leads to genotype-dependent cell biology in a way that increases disease risk.

One of the joys of my career is being a part of multidisciplinary teams in which my colleagues and I use our individual strengths and expertise to perform research together that none of us could do alone. In this way, we have had the privilege to make numerous notable discoveries.

For example, I’ve been part of teams that identified the genetic variations near the esophageal-specific gene CAPN14 that increase the risk for eosinophilic esophagitis. I was also part of a team that identified the interaction of transcriptional regulators of the Epstein Barr virus with autoimmune disease risk variants. On another team, we identified estrogen receptor's genotype-dependent interaction with genetic variants that increase risk for pre-term birth.

I share a wet lab with Dr. Matthew Weirauch at Cincinnati Children’s. The Weirauch lab develops new computational tools to understand transcriptional regulation. A major strength of this arrangement is the mixing of experimental and computational backgrounds among topics, and therefore trainees.

The multidisciplinary structure among the principle investigators and their teams provides the conceptual synergy driving many collaborative projects. Dynamic interactions between people performing functional genomic experiments and the people developing the analytical pipelines in this lab enables high-quality, robust scientific discovery. We have made incredible progress over the past few years toward identifying the transcriptional mechanisms that drive genotype-dependent gene expression and disease risk.

During my career, I’m proud to have received the Cincinnati Children’s 2020 Mentoring Achievement Award, the 2018 Recognition of Excellence Award, and the 2016 Darrell Goll Award. The Darrell Goll Award recognizes the most outstanding new investigator publishing in the calpain field over the past three years. I am also pleased to serve as a coordinator for the Schmidlapp Young Women Scholars Program, which provides career support to women undergraduate scholars at Cincinnati Children’s.

Research Interests

Genetic basis of lupus; genetic basis of eosinophilic esophagitis; immunological mechanisms mediating genetic association with disease

Visit the Kottyan Lab.

Academic Affiliation

Assistant Professor, UC Department of Pediatrics

Departments

Allergy and Immunology, Allergy and Immunology

Science Blog

My Education

BA: Chemistry and Cell Biology, Huntingdon College, Montgomery, AL, 2005.

PhD: Immunobiology, University of Cincinnati, Cincinnati, OH, 2010.

My Publications

Selected Publication

Genetic variants at the 16p13 locus confer risk for eosinophilic esophagitis. Kottyan, LC; Maddox, A; Braxton, JR; Stucke, EM; Mukkada, V; Putnam, PE; Abonia, JP; Chehade, M; Wood, RA; Pesek, RD; et al. Genes and Immunity. 2019; 20:281-292.

Genetic, Inflammatory, and Epithelial Cell Differentiation Factors Control Expression of Human Calpain-14. Miller, DE; Forney, C; Rochman, M; Cranert, S; Habel, J; Rymer, J; Lynch, A; Schroeder, C; Lee, J; Sauder, A; et al. G3-Genes Genomes Genetics. 2019; 9:g3.200901.2018-g3.200901.2018.

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus. Patel, ZH; Lu, X; Miller, D; Forney, CR; Lee, J; Lynch, A; Schroeder, C; Parks, L; Magnusen, AF; Chen, X; et al. Human Molecular Genetics. 2018; 27:2392-2404.

Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Harley, JB; Chen, X; Pujato, M; Miller, D; Maddox, A; Forney, C; Magnusen, AF; Lynch, A; Chetal, K; Yukawa, M; et al. Nature Genetics. 2018; 50:699-707.

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. Zhang, G; Feenstra, B; Bacelis, J; Liu, X; Muglia, LM; Juodakis, J; Miller, DE; Litterman, N; Jiang, P; Russell, L; et al. The New England journal of medicine. 2017; 377:1156-1167.

Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay (EMSA) and DNA-affinity Precipitation Assay (DAPA). Miller, DE; Patel, ZH; Lu, X; Lynch, AT; Weirauch, MT; Kottyan, LC. Jove-Journal of Visualized Experiments. 2016; 2016.

Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. Lu, X; Zoller, EE; Weirauch, MT; Wu, Z; Namjou, B; Williams, AH; Ziegler, JT; Comeau, ME; Marion, MC; Glenn, SB; et al. The American Journal of Human Genetics. 2015; 96:731-739.

The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. Kottyan, LC; Zoller, EE; Bene, J; Lu, X; Kelly, JA; Rupert, AM; Lessard, CJ; Vaughn, SE; Marion, M; Weirauch, MT; et al. Human Molecular Genetics. 2015; 24:582-596.

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Kottyan, LC; Davis, BP; Sherrill, JD; Liu, K; Rochman, M; Kaufman, K; Weirauch, MT; Vaughn, S; Lazaro, S; Rupert, AM; et al. Nature Genetics. 2014; 46:895-900.

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration. Liu, X; Helenius, D; Skotte, L; Beaumont, RN; Wielscher, M; Geller, F; Juodakis, J; Mahajan, A; Bradfield, JP; Lin, FT; et al. Nature Communications. 2019; 10.