Autoimmune diseases have a complex mode of inheritance, with studies showing that siblings and family members of people with diseases like Crohn’s, ulcerative colitis, and diabetes have a significantly increased risk of being affected, yet the pattern does not fit the simple single-gene model. Rather, these conditions, like most human traits, are influenced by hundreds of small single nucleotide polymorphisms (SNPs) located in the 99% of the genome that does not encode protein.

Presumably, these causal SNPs alter transcription protein binding, resulting in changes in the expression level of protein- and RNA-coding genes in specific contexts and cell types. A powerful approach to identify culprit SNPs is the genome-wide association study (GWAS), which compares millions of SNPs in affected individuals to a control population.

Dr. Cardinale's research focuses on characterizing the protein- and RNA-coding genes whose expression is altered by the disease-causing SNPs and the mechanism by which transcription factors recognize the SNPs to produce changes in gene expression. He recently examined a causal SNP for inflammatory bowel disease (IBD) in the promoter region of the Janus kinase 2 (JAK2) gene. Using CRISPR/Cas9 genome editing, he determined that JAK2 expression is only minimally impacted by the SNP, but this results is large changes in the function of the JAK-STAT signaling pathway in helper T cells. Using mass spectrometry, Dr. Cardinale identified the transcription factors, CUX1 and RBPJ, which bind differentially to the risk and non-risk alleles of the SNP.

Among his accomplishments, Dr. Cardinale:

• Found an enrichment of functionally defective coding variants in Decoy Receptor 3 (TNFRSF6B) in early-onset IBD
• Studied function of hereditary mutation in NOTCH4 receptor in familial systemic sclerosis
• Performed transcriptomic and pathway-based analysis of gene expression and genetic risk in ulcerative colitis
• Studied mechanism and consequence of noncoding polymorphism in JAK2 promoter in Jurkat T cells

BA, Harvard University (Biomedical Sciences), 1999

PhD, New York University (Cellular and Molecular Biology), 2008

MD, New York University, 2010

Fellowship, Children's Hospital of Philadelphia (Molecular Genetics), 2015

Scientist

American Society of Human Genetics, 2015-