Stottmann Lab
The long-term goals of the Stottmann Lab are to understand the genes and molecular mechanisms guiding normal development of both the brain and face. Dr. Stottmann and his team seek to understand the genetic basis of human birth defects involving these tissues. They use a combination of human genetics and animal models to identify genes required for normal development and then study the molecular consequences of disrupting their function in the developing embryo.
Current Projects
The Stottmann Lab is currently collaborating with clinical partners to directly study patients with congenital malformations of the brain and face and actively enrolling in research protocols in each of these areas. The team is using whole genome sequencing to identify potentially causal genetic variants in these patients. The lab then employs CRISPR/Cas9 genome editing technology, molecular embryology, animal models, and induced pluripotent stem cells (IPSCs) to understand how these variants lead to malformations.
As part of this work, the Stottmann Lab is pursuing a number of collaborations across the hospital and with institutions around the world. The complementary tools of genome sequencing, CRISPR genome editing, animal models and stem cell technologies offer almost limitless chances for discovery.
Primary cilia are organelles with a now established role in transducing many canonical developmental signaling pathways. Deficits in ciliary form and/or function lead many human conditions and are collectively called “ciliopathies.” Following the genetics behind a number of our phenotypes has led the Stottmann Lab team into the study of several genes required for normal cilia form and/or function.
The alien mutation was previously identified in a mutagenesis screen (Herron et al., Nat Genetics 2002). Positional cloning revealed this to be a null mutation in the gene Ttc21b, which is required for protein transport within the primary cilium (Tran et al., Nat Genetics 2008). The alien mutant also has a severe brain patterning defect (Stottmann et al., Dev Biol, 2009). The role of Ttc21b in the developing forebrain and craniofacial tissues, and the role of cilia in development more broadly, is a major focus within the laboratory. One direction of this project is a tissue specific ablation of Ttc21b and other primary cilia genes in the in the developing forebrain and craniofacial tissues.
Evidence from human genetics studies suggest Ttc21b is a node in a larger ciliary signaling network. The Stottmann Lab team is studying how these genes interact through studies in the mouse and in vitro. The team is also using a forward genetic approach to identify novel loci interacting with Ttc21b in mammalian development and disease and has used a Quantitative Trait Locus analysis to identify a gene it now believes at least partially explains the effects of genetic background on the alien forebrain mutation.
Tubulin proteins are the building blocks of microtubules, a key element of the cellular cytoskeleton. Research has shown in mice and humans that variants in tubulins lead to drastic malformations of cortical development. The tubulin genes together make up a family of genes with high-sequence similarity and, often, adjacent positions in the genome. The Stottmann Lab uses genome editing techniques to make a series of alleles to test the requirements for these genes as this has never been tested. Its team is also generating new models of human disease variants and constructing a new tool to address expression and regulation of tubulin genes.
The rudolph mutation was recovered in another ENU mutagenesis screen in the Beier Lab (Stottmann et al., Genetics, 2011). Positional cloning identified an intronic mutation creating a hypomorphic allele of the gene hydroxysteroid (17-beta) dehydrogenase 7 (Hsd17b7; Stottmann et al., PLoS Genetics, 2011). Further studies of the rudolph mutation demonstrated for the first time in a genetic, in vivo, animal model a requirement for sterol metabolism in proper Sonic Hedgehog intracellular signal transduction. The rudolph mutants have a striking defect in tissue organization throughout the CNS which is not due to dysregulation of the Shh pathway. Current efforts in the lab are aimed at understanding the molecular mechanisms underlying this defect. This will contribute to a greater understanding of the role of cholesterol metabolism in cortical development.
The lab primarily uses this forward genetic approach to identify genes not previously known to be required in development. They use the chemical mutagen ENU to create random mutations in the genome and breed potential mutations to homozygosity to create recessive developmental phenotypes. A combination of cutting-edge genomics and positional cloning is used to identify the mutated gene leading to the phenotypes. This turns out to be a relatively efficient tool for gene discovery in development (see Stottmann et al., 2011; Stottmann and Beier 2010). The Stottmann Lab continues to use ENU mutagenesis to create novel mutations and will increasingly employ transgenic lines to more specifically query various aspects of neuronal specification and migration. Work on this project is funded by the Cincinnati Children's Research Foundation and the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH).
Research Funding
- NIH/NIGMS R35GM131875: Molecular analysis of primary cilia protein in human development and disease, Principal Investigator
- NIH/NIDCR R01DE027091: Forward genetic analysis of congenital craniofacial malformations, Principal Investigator
- NIH/NICHD R03HD094882: Role of Cholesterol Biosynthesis in Development, Principal Investigator
Meet Our Team
Rolf Stottmann, PhD
Principal Investigator
Rolf.Stottmann@NationwideChildrens.org
Rolf Stottmann, PhD, is a professor in the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital and The Ohio State University College of Medicine. Dr. Stottmann has an enduring interest in the genetics of structural birth defects. He is especially focused on structural brain malformations and disrupted craniofacial skeletal development: congenital malformations of craniofacial development. He originally trained using mouse genetics to study these issues but has recently added human sequencing projects to his lab portfolio. The lab now uses a combination of human and mouse genetics to identify and study rare genetic variants which cause these congenital malformations. Genome editing tools allow the group to directly model patient variants to assess pathogenicity, study animal models in depth and potentially design therapeutic intervention strategies.
Dr. Stottmann received his bachelor’s degrees in Physiology and Neurobiology and his master’s degree in Developmental Neurobiology from the University of Maryland. Dr. Stottmann pursued dissertation work in the Department of Cell Biology at the Duke University School of Medicine followed by postdoctoral training at the Brigham & Women’s Hospital Division of Genetics and Harvard Medical School. In 2011, Dr. Stottmann set up his first laboratory research program at Cincinnati Children’s Hospital in the Division of Human Genetics with a joint appointment in the Division of Developmental Biology.
Kurt Reynolds, PhD
Postdoctoral Scientist
Kurt.Reynolds@NationwideChildrens.org
Kurt recently completed his doctorate at The University of California, Davis, where he investigated Wnt signaling in craniofacial development and its roles in the etiology of oral clefts. He joins the Stottmann Lab as a postdoctoral scientist where he will use mouse models to characterize the developmental contributions of two genes whose homologs are implicated in rare human craniofacial disorders.
Jennifer Watts, PhD
Postdoctoral Scientist
Jennifer.Watts@NationwideChildrens.org
Jennifer Watts, PhD, is a postdoctoral scientist in the the Stottmann Lab. Her current research focuses on the genetic and molecular origins of craniofacial abnormalities.
Dr. Watts received her bachelor’s degree in Biology from the University of Texas at San Antonio in 2016, completing her undergraduate thesis in cancer biology, and her doctorate degree in Molecular, Cellular and Integrative Physiology from Michigan State University in 2021. Her dissertation focused on the effects of Zika virus infection on embryo development utilizing mouse and stem cell models. Dr. Watts completed additional developmental biology training at Cold Spring Harbor Laboratories and the Reproductive and Developmental Sciences Training Program at Michigan State University with three years of funding through the National Institutes of Health (NIH).
Thamara Dayarathna
Research Scientist
Thamara.Dayarathna@NationwideChildrens.org
Thamara earned her bachelor’s degree in Chemistry from University of Kelaniya, Sri Lanka and her doctoral degree in Plant Chemistry from University of Greenwich, UK. Then she moved to Canada and gathered post doctoral experience in Biochemistry and Molecular Biology from University of Western Ontario. During her postdoctoral experience, Thamara won an industrial scholarship to join with a biotech company to develop DNA aptamer-based biomarkers for cancer diagnosis and mycotoxin detection in various food types. Her translational research work conducted at St Joseph’s Hospital in Ontario was intriguing. This work led her to discover nutraceutical drug candidate for kidney stone disease and to develop non-invasive biomarkers to detect various cancer types and Alzheimer’s disease. Throughout her research journey she is qualified for high throughput drug discovery animal model development, personalized drug discovery using various cancer xenografting models, biomarker development for early diagnosis of both cancer and neurodegenerative diseases. In the Stottmann Laboratory, Dr. Dayarathna is researching mechanisms involved in structural birth defects at genotypic, transcriptional, posttranscriptional, translational, and post-translational levels using animal models as well as patient derived human iPSC research models.
Paul Iyyanar
Research Scientist
Paul.Iyyanar@NationwideChildrens.org
Paul joined the lab as a research scientist in August 2023 and has a longstanding interest in craniofacial development. During his doctoral program at the University of Saskatchewan, Canada, Paul investigated the mechanism of cleft palate pathogenesis due to mutations in the Hoxa2 gene. During his postdoctoral work at Cincinnati Children's Hospital, he characterized several transgenic mouse lines of Alx transcription factors and identified the developmental and patterning basis of frontonasal dysplasia (median cleft syndrome). In the Stottmann Lab, Paul will be using a combination of human genetics and mouse transgenic approaches to delineate genetic, cell and developmental mechanisms of craniofacial malformations.
Iftekhar Showpnil
Bioinformatics Analyst I
Iftekhar.Showpnil@NationwideChildrens.org
Iftekhar is a bioinformatics analyst in the Stottmann Lab performing variant analysis for the craniofacial malformations human genetics research protocol launched by Dr. Rolf Stottmann at the Institute for Genomic Medicine (IGM), Nationwide Children's Hospital. He completed his doctorate with Dr. Stephen Lessnick at the Center for Childhood Cancer, Nationwide Children's Hospital. As part of his graduate studies, Iftekhar worked with several genomic and epigenetic datasets including Hi-C, 4C, CUT&TAG, ChIP-seq, ATAC-seq, and RNA-seq to understand the effects of the EWS::FLI oncogenic transcription factor on chromatin organization and gene expression in Ewing sarcoma. Iftekhar is highly interested in studying disease mechanisms using genomics and bioinformatics tools and is currently integrated with the research genomics group at IGM (led by Daniel Koboldt) where he routinely works with genomic datasets (WES, WGS, and RNA-seq) to identify disease causing variant(s) in patient families enrolled in various human genetics research protocol at IGM.
Nicole Costantino
Research Assistant
Nicole.Costantino@NationwideChildrens.org
Nicole Costantino joined the Stottmann Lab as a research assistant in August 2021. Nicole recently graduated from The Ohio State University with a bachelor’s degree in Biology and a minor in Business. During college, Nicole enjoyed studying Genetics and Microbiology, and she is looking to further her education.
JES-Rite Michaels
Research Assistant
JES-Rite.Michaels@NationwideChildrens.org
JES-Rite Michaels joined the Stottmann Lab as a research assistant in August 2021. She recently graduated from Howard University with a bachelor’s degree in Biological Sciences with minors in Chemistry and Health Education. JES-Rite has always been interested in disease etiology and pediatrics. She is excited to explore her interests researching the genetics and molecular mechanisms behind structural birth defects of the brain and face.
Andrew Vontell
Research Assistant
Andrew.Vontell@NationwideChildrens.org
Andrew Vontell joined the Stottmann Lab in 2022 and studies congenital craniofacial malformations and development. Andrew graduated from The Ohio State University with a bachelor’s degree in Biochemistry and has previous research experience in Plant Pathology.
Logan Willeke
Research Assistant
Logan.Willeke@NationwideChildrens.org
Logan Willeke joined the Stottmann Lab as a research assistant in September 2023. Logan graduated from The Ohio State University with a bachelor’s degree in Molecular Genetics. He is excited to gain more experience with research before pursuing a master’s degree in Genetic Counseling.
Jesus Leal
Research Assistant
Jesus.Leal@NationwideChildrens.org
Jesus M. Leal joined the Stottmann Lab as a research assistant in July 2023. Jesus recently graduated from Loyola University Chicago with a bachelor’s degree in Biology and a minor in History. As an undergraduate, Jesus conducted research in Ecology and Evolution. He is excited to pursue his other research interests as he studies the development of congenital brain defects.
Rebekah Rushforth
Graduate Student
Rebekah.Rushforth@NationwideChildrens.org
Rebekah Rushforth is a student in the Biomedical Sciences Graduate Program at The Ohio State University completing her graduate work in the Stottmann Lab.
Bekah graduated from Brigham Young University with a bachelor's degree in Genetics, Genomics, and Biotechnology. She became interested in pursuing rare pediatric neurological disorders while working as a lab tech at the University of Utah. Her research focus is on the genetic mechanisms of craniofacial disorders and basal ganglia development.
Ramon Macias
Research Student
Ramon.Macias@NationwideChildrens.org
Ramon is a graduate student in The Ohio State’s Molecular, Cellular and Developmental Biology doctorate program. Ramon graduated from the University of Illinois Urbana-Champaign with a bachelor’s degree in Bioengineering and had been working at a diagnostic laboratory, Alverno Laboratories, for two years prior to joining the Stottmann Lab. His research in the lab is primarily focused on elucidating the role of α/β-tubulin isotypes in embryonic development, with a particular interest in cortical development.
Bryan Crase
Undergraduate Student
Bryan.Crase@NationwideChildrens.org
Bryan Crase is a third-year molecular and cellular neuroscience undergraduate at The Ohio State University who joined the lab in January 2022. He has since worked on projects that focus on genetic influences of the neocortex and the cerebellum during development. He is currently studying the epigenetic effect of a specific bromodomain on neocortical development. Is a current Choose Development! fellow through the Society of Developmental Biology. He plans to pursue a medical degree and doctorate after graduation.
Join Our Team
The Stottmann Lab is committed to mentoring the next generation of scientists and welcomes motivated undergraduate, graduate and postdoctoral researchers seeking research training opportunities. If you're interested in our work, please complete the contact form below to connect with us.