Holly A. Stessman, PhD
School of Medicine
- Human genetics, genomics, molecular biology, autism spectrum disorder, tissue culture systems
- Assistant Professor
Dr. Stessman received her Bachelor of Science degree from Clarke University in Dubuque, IA with a double major in Biology and Biochemistry. She received her graduate degree under the mentorship of Dr. Brian Van Ness at the University of Minnesota-Twin Cities and continued on to do a post doc in Dr. Evan Eichler's group at the University of Washington in Seattle, WA in Genome Sciences. Dr. Stessman joined the faculty at Creighton University in 2016 where she leads a research group identifying and functionally characterizing genetic variation that contributes to complex disease biology with the goal of finding new drug targets that may stop disease progression and improve patient quality of life.
- Clarke University, B.S. Biology and Biochemistry (summa cum laude), 2004-2008
- University of Minnesota (Twin Citites), Ph.D. Molecular Cellular Developmental Biology and Genetics, 2008-2013
- University of Washington, Postdoctoral Fellowship in Genome Sciences, 2013-2016
- Targeted sequencing identifies 91 neurodevelopmental disorder risk genes with autism and developmental disability biases.
Abstract: Gene-disruptive mutations contribute to the biology of neurodevelopmental disorders (NDDs), but most pathogenic genes are not known. We sequenced 208 candidate genes from >11,730 patients and >2,867 controls. We report 91 genes with an excess of de novo mutations or private disruptive mutations in 5.7% of patients, including 38 novel NDD genes. Drosophila functional assays of a subset bolster their involvement in NDDs. We identify 25 genes that show a bias for autism versus intellectual disability and highlight a network associated with high-functioning autism (FSIQ>100). Clinical follow-up for NAA15, KMT5B, and ASH1L reveals novel syndromic and non-syndromic forms of disease., Nature Genetics
Research and Scholarship Interests
- The focus of the Stessman laboratory is to identify and functionally characterize genetic “drivers” of complex human diseases to find new drug targets that may stop disease progression and improve patient quality of life. Specifically we focus on genetic diversity in two disease systems, autism spectrum disorder and cancer. As a functional genomics laboratory, we utilize a diverse array of tools, including next-generation sequencing technologies, mouse modeling, human cell line modeling, CRISPR genome-engineering, high-throughput small-molecule screening, and classical molecular and cell biology approaches. Computational resources also play a central role in multiple aspects of our research.
Current Research Projects
- The major objective of our current work is to determine the functional relevance of disease-associated mutations that we have identified in autistic patients moving beyond genetic subtypes to understand the biology of the disease. Using CRISPR/Cas9 genome engineering technology, we are modeling two classes of mutations in human cell lines: (1) early truncating mutations (a model of haploinsufficiency) and (2) specific mutations that have been observed in patients. By modeling these types of mutations in human induced pluripotent stem cells (iPSCs), we can observe what effects these variants have on neural precursors and during neuronal differentiation which can be studied in the cell culture dish.