My research focuses on the identification and characterization of genes and their genetic mechanisms involved in the causation and pathology of neurodevelopmental disorders including autism spectrum disorder. To study the disease specific mechanisms and test potential therapeutic approaches, I use cutting-edge technologies such as patient-derived induced pluripotent stem cell (iPSC) lines and CRISPR/Cas9-based gene editing followed by differentiating to 3-dimensional culture that resembles human brain tissue.
Individuals with ASD have increased risks of developing several other health complications, including various cardiovascular problems. Recent studies highlighted that genes already implicated in autism were also associated with congenital heart diseases, which suggests that some genes may have dual roles in regulating the development of the brain and the heart. Therefore, I also focus on the expression and function of candidate gene(s) with a role in converging pathways in brain and heart development by using the patient derived iPS cells and subsequently differentiating them to brain organoids and cardiomyocytes.
- Made significant contributions to the understanding of genetic mechanism of autism; was a co-author of the first report on exome sequencing and copy number variation analysis in ASD cases and their phenotypically discordant
- Cloned the first gene demonstrating dominant Mendelian inheritance of a Tourette syndrome phenotype. This work, published in the New England Journal of Medicine, pointed for the first time to the involvement of histaminergic neurotransmission in the generation or modulation of tics.
- Identified a novel DIAPH1 gene, expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division, responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature in a multiply-affected consanguineous family.
Adife Gulhan Ercan-Sencicek
Instructor, Masonic Medical Research Institute
Email – , Phone – 315-624-7479
After earning my Ph.D. degree in Akdeniz University in 2000 where I studied the genetic diversity in Turkish sesame (Sesamum indicum L.) populations, I completed a second Master’s degree in Cellular and Molecular Biology at University of New Haven 2004 working on finding the early markers in breast cancer. I started my postdoctoral training in the Yale University, Department of Genetics and Child Study Center in Dr. Matthew State’s laboratory where I worked on the identification and characterization of genes and genetic mechanisms involved in neurodevelopmental disorders, including autism, intellectual disability, and Tourette syndrome. During my postdoctoral fellowship, I have learned a great deal about how researchers approach the genetics of complex disorders. I have initiated and participated in several projects, including the study of consanguineous and/or multiply affected families ascertained for autism spectrum disorder (ASD), Tourette syndrome, intellectual disability (ID). After completing the postdoctoral training, I stayed in Dr. State’s lab as an Associate Research Scientist. Later, I was offered a great opportunity to work with Dr. Murat Gunel in the Neurosurgery at Yale school of Medicine where I led the project on whole exome sequencing of consanguineous families from Egypt and Turkey to identify genetic variant conferring autism risk and evaluate the overlap in risk loci for inbred versus outbred autism spectrum disorder populations. I also established the zebrafish animal modeling in the Gunel lab for functional evaluation of strong candidate genes involved in the pathophysiology of intracranial aneurysm. Since September 2018, I have been working as an instructor in Dr. Maria Kontaridis’s lab in the Masonic Medical Research Institute. I plan to use my skills in human genetics to continue gene discovery efforts and analyze the functional consequences of the mutations I discover. My long term plan is to master the skills that will help me to understand the expression and function of candidate gene(s) with a role in converging pathways in brain and heart development by using the patient derived induced pluripotent stem cells which will help us to develop therapeutics. Then, I aim to fully characterize patient mutations through in vivo studies. Despite being primarily in research, I value communicating with the students, sharing my knowledge and experience, and learning from the fresh perspectives that newcomers bring. Therefore, I have also been teaching in Utica College's Biology Department as an adjunct since September, 2018.
Honors and Prizes:
Top ten scientific breakthroughs of the year
SLITRK1 first reported gene that is associated with Tourette syndrome
Key Accomplishments and breakthroughs: 20 key discoveries, advances and developments in Tourette and Tic Disorders
Tourette Association in America
HDC is the first gene that identified a link between histaminergic neurotransmission and tics in humans
Completed Research Support
Identifying the genes responsible for ASD and/or ID using multiplex families
NCATS NIH UL1 TR000142 & KL2 TR000140
Yale Center for Clinical Investigation (YCCI) Junior Faculty Scholar (PI: Robert Sherwin)
The goal of this study is to find susceptibility genes in individuals with autism spectrum disorder (ASD) and intellectual disability (ID) by studying families in which the disorder is transmitted in a Mendelian fashion
Molecular Genetic Pathogenesis of Intracranial Aneurysms
The Goal of this study was identification and functional verification of variants associated with Intracranial aneurysm to demonstrate their biological effects.
Disease Gene Discovery in Structural Brain disorders
The major goal is to identify the molecular and genetic basis of structural brain malformations
Integrating the genomics of Autism Spectrum Disorders (ASD) in consanguineous and "idiopathic" families
Key Personal (PI: Murat Gunel)
The goal of the study is to identify novel, rare genetic variants in ASD by employing homozygosity mapping and whole exome sequencing and further evaluate the overlap risk loci for inbred versus outbred ASD populations.