Molecular Genetics of Neurodevelopment in Health and Disease
We are fascinated by the interplay between autism, neuronal activity, and circadian rhythm!
Research Interests
Chromatin regulators and transcription factors orchestrate neuronal gene expression that gives rise to complex human behaviors. These processes often go awry in neurodevelopmental conditions such as Autism Spectrum Disorders (ASDs). The goal of our lab is to gain fundamental insights into brain development and ASD pathogenesis to develop new therapeutic strategies. We will use a multi-disciplinary approach to dissect a group of molecularly related ASD disease models, drawing on our expertise in chromatin biology, biochemistry, chronobiology, mouse and human genetics, and neural engineering. We are particularly interested in the following questions:
- What is the molecular basis of phenotypic convergence and divergence in heterogenetic ASDs?
- How does neural activity respond and contribute to behaviors in health and disease? Can we modulate neural activity to treat syndromic ASDs?
- Is there a genetic basis for sleep problems in ASDs and can other ASD symptoms be ameliorated by correcting circadian and sleep rhythm?
Molecular Basis of Autism Spectrum Disorders (ASDs)
Autism Spectrum Disorders (ASDs) affect communication, learning, and behavior, with a diagnosis rate of one in 36 children in the United States. Despite knowing the genetic basis, the molecular mechanism of these disorders remains elusive. We have identified a novel chromatin complex, the TCF20/PHF14 complex, which plays a crucial role in brain development and ASD pathogenesis. In collaboration with Robert Tjian's group at UC Berkeley, we are employing mouse models, iPSC-derived neurons, and single-molecule imaging to investigate the convergent and divergent roles of the TCF20/PHF14 complex in brain development and function.
Neuronal Activity and Brain Development
Many ASD features manifest early in life when activity-dependent signaling promotes neuron maturation and function in response to sensory and learning experiences. We found many disease-related chromatin factors promote activity-dependent gene induction during neural activity, dysregulation of this process could be rooted in the pathogenesis of ASDs. These findings provided us with an excellent opportunity to examine how activity-dependent signaling regulates brain function under healthy and ASD disease conditions.
Genetic Basis of Sleep Problems in ASDs
Up to 80% of individuals with ASDs experience sleep disturbances. Growing evidence suggests that sleep disturbances, beyond being a consequence of ASDs, can also impair brain development and increase ASD risk. While the mechanisms underlying this bidirectional regulation are poorly understood, we established new mouse models and will combine neurogenetics and chronobiology to tease apart the molecular interplay between the circadian clock and ASDs and reveal new therapeutic options.
Lab members
Jian Zhou, Ph.D. Principal Investigator
Assistant Professor of Human Genetics and Pediatrics
Email: jzhou51@emory.edu
Jian Zhou received his Ph.D. in biology from Texas A&M University in the lab of Dr. Paul Hardin. He then performed his postdoctoral studies in the lab of Dr. Huda Zoghbi at Baylor College of Medicine.
Jian Zhou is a Duncan NRI Zoghbi Scholar and an NIH/NINDS K99/R00 Pathway to Independence Award recipient.
Outside the lab, Jian enjoys reading, hiking, and classical music.
Weilan Lin, M.S.
Research specialist
Email: weilan.lin@emory.edu
Weilan is the lab manager and research specialist in Dr. Zhou's lab. Before joining Zhou Lab, Weilan worked in Dr. Jinhu Wang's lab at Emory as a technician. She combines her engineering background with a passion for molecular biology. Pleasure to explore the miraculous and beautiful molecular genetics.
Outside of work, she enjoys running and spending time with her two lovely daughters.
Yongji Wu, Ph.D.
Postdoctoral fellow
Email: yongji.wu@emory.edu
Yongji Wu received her Ph.D. in Basic Veterinary Medicine from Northwest A&F University in the lab of Dr. Shanting Zhao. She then continued her postdoc training on autism research in the lab of Dr. Liping Wang at Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences.
Yongji is interested in the relationship between genes and background in ASD and the convergence and divergence pathways that are critical during brain development and disease pathogenesis.
Outside the lab, Yongji enjoys reading, listening to music, and exercising.
Gaea Dominguez
Graduate student (Woodruff Fellow and T32 awardee)
Email: gaea.charlize.dominguez@emory.edu
Gaea Dominguez is a PhD student in the GMB Program at Emory University. She received her B.S. in Biology from the University of Massachusetts Boston in 2023. During her undergraduate studies, she discovered her passion for developmental biology through her time in Dr. Kellee Siegfried’s lab. Gaea’s research interests include investigating the dynamic genetic and epigenetic landscapes during organismal development, especially in the context of neurodevelopmental disorders such as autism.
Outside the lab, Gaea enjoys spending time with her cats (Momo and Coco), experimenting with various arts and crafts, playing video games, fishing, and hiking.
Kevin Fuentes
Rotating graduate student
Kevin Fuentes is a PhD student in the NS Program at Emory University. He received his B.S. in Behavioral Neuroscience from Lehigh University in 2022. During his undergraduate studies, he discovered his passion for neurological disorders through his time in Dr. Neal Simon’s lab. Following graduation, Kevin completed a post-bac at NIH, working alongside Dr. Diana Bianchi and Dr. Laura Baxter on establishing an in vitro model system using Neural Progenitor Cells (NPC) to identify safe and effective drugs for trisomy 21 (T21). Kevin’s research interests include investigating the molecular changes occurring in the brain, especially in neurodevelopmental disorders such as ASDs.
Outside the lab, Kevin enjoys cooking with friends, participating in soccer and tennis, and hosting movie nights with friends!
Caitlin Fix
Rotating graduate student
Caitlin is an Emory neuroscience graduate student currently rotating in Dr. Zhou’s lab. Prior to Emory, she received her undergraduate degree from Georgia Tech, where she studied peripheral nerve injury and Charcot-Marie-Tooth disease. To that end, she is interested in learning more about the genetic and cellular underpinnings of neurological disorders, such as autism.
Outside of lab, Caitlin enjoys hiking, traveling, and cooking.
Bryan Chacon Vazquez
Undergraduate Researcher
Bryan is an undergraduate student at Emory, majoring in Chemistry, and joined the Zhou lab as an undergraduate research assistant. Bryan wants to learn more about biochemistry and its relationship to human diseases.
Outside the lab, Bryan enjoys playing soccer and outdoor activities.
Livia Peng
Undergraduate Researcher
Livia is an undergraduate student majoring in biology at Emory, and she joined the Zhou lab as an undergraduate research assistant. With a passion in medicine and healthcare, Livia is also interested in studying the molecular basis and the neurodevelopmental aspects that gives rise to various health conditions in diseases.
Outside of the lab, Livia enjoys singing, listening to music, and playing badminton.
Eskender Seyoum
Undergraduate Researcher
Eskender is an undergraduate student at Emory majoring in Biology and minoring in German. He joined the Zhou lab as an undergraduate research assistant and is interested in the role of chromatin complexes in neuronal activity and their interaction with other proteins and cell factors. He wants to discover the molecular mechanisms behind ASD and what this might say about other neurodevelopmental disorders. Outside of the lab, Eskender likes learning languages, trying out new food, and watching sports.
Your name here!
Lab alumni - thanks and we miss you!
Joey Xie 2024 Vanderbilt undergraduate student
Amanuel Abel 2024 Emory undergraduate student
Publications
- Jian Zhou*, Claudia Cattoglio*, Yingyao Shao*, Harini P. Tirumala, Carlo Vetralla, Sameer S. Bajikar, et al "A novel pathogenic mutation of MeCP2 impairs chromatin association independent of protein levels." Genes & Development. 2023, doi10.1101/gad.350733.123
- Highlighted in Genes Dev
- Jian Zhou, Hamdan Hamdan, Hari Krishna Yalamanchili, Kaifang Pang, Amy E. Pohodich, Joanna Lopez, et al "Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders." Proc Natl Acad Sci U S A .. 2022 Jan 25;4 Pubmed PMID: 35074918
- Featured in autism research news on SPECTRUM
- Sameer S Bajikar, Ashley G Anderson, Jian Zhou, Mark A Durham, Alexander J Trostle, Ying-Wooi Wan, Zhandong Liu, Huda Y Zoghbi "MeCP2 regulates Gdf11, a dosage-sensitive gene critical for neurological function." eLife. 2023 Feb 27; Pubmed PMID: 36848184
- Gustavo B S Rivas*, Jian Zhou*, Christine Merlin, Paul E Hardin "CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the putative Drosophila ortholog of CLOCK INTERACTING PROTEIN CIRCADIAN." Curr Biol. 2021 Jul 30; Pubmed PMID: 34331859
- Aya Ito-Ishida, Steven A Baker, Roy V Sillitoe, Yaling Sun, Jian Zhou, Yukiteru Ono, Junichi Iwakiri, Michisuke Yuzaki, Huda Y Zoghbi "MeCP2 Levels Regulate the 3D Structure of Heterochromatic Foci in Mouse Neurons." J Neurosci.. 2020 Nov 4;40(45):8746-8766. Pubmed PMID: 33046553
- Kaifang Pang, Li Wang, Wei Wang, Jian Zhou, Chao Cheng, Kihoon Han, Huda Y Zoghbi, Zhandong Liu "Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders." Genome Res.. 2020 Jun 1;30(6):835-848. Pubmed PMID: 32554779
- Parul Agrawal, Jerry H Houl, Kushan L Gunawardhana, Tianxin Liu, Jian Zhou, Mark J Zoran, Paul E Hardin "Drosophila CRY entrains clocks in body tissues to light and maintains passive membrane properties in a non-clock body tissue independent of light." Curr Biol.. 2017 Aug 21;27(16):2431-2441. e3. Pubmed PMID: 28781048
- Jian Zhou, Wangjie Yu, Paul E Hardin "CLOCKWORK ORANGE enhances PERIOD mediated rhythms in transcriptional repression by antagonizing E-box binding by CLOCK-CYCLE." PLoS Genet.. 2016 Nov 4;12(11):e1006430. Pubmed PMID: 27814361
- Jian Zhou, Wangjie Yu, Paul E Hardin "ChIPping away at the Drosophila clock." Methods Enzymol.. 2015 Jan 1;551:323-347. Pubmed PMID: 25662463
- Huan Nan Wang, Yan Xu, Ling Jie Tao, Jian Zhou, Meng Xi Qiu, Yu Hang Teng, Feng Jiao Deng "Identification and characterization of the pumilio-2 expressed in zebrafish embryos and adult tissues." Mol Biol Rep.. 2012 Mar;39(3):2811-2819. Pubmed PMID: 21660475
- Yan Xu, Huannan Wang, Jian Zhou, Yong Lei, Yaping Zhou, Qiwen Yang, Ding Ye, Wenhua Li, Fengjiao Deng "Zebrafish Nanos interacts with and regulates the phosphorylation of Mylz2." Biochimie.. 2010 Dec 1;92(12):1812-1817. Pubmed PMID: 20673786
Lab News
Eskender Seyoum joined the Zhou lab in July 2024. Welcome Eskender!
Gaea gave a fantastic talk at the 2024 GMB Retreat. Great job Gaea, You made us proud!
Jian presented at the 2024 DOHG Department Retreat, and we all enjoyed the science and a cruise on Lake Lanier!
Joey has finished his summer internship and is heading back to Vanderbilt. Good luck, Joey - we will miss you!
Livia Peng joined the Zhou lab in July 2024. Welcome Livia!
Jian gave a research talk at the 11th SMS Research Symposium in Dallas, Texas, 2024.
Gaea was awarded a travel scholarship from the PRISMS Foundation to attend the 11th SMS Research Symposium in Dallas, Texas, this July. Way to go, Gaea!
Gaea Dominguez officially joined the Zhou lab in May 2024 after her rotation. Welcome Gaea!
We did our first experiment! And we celebrated it!
Amanuel Abel joined the Zhou lab in March 2024. Welcome Amanuel!
Dr. Yongji Wu joined the Zhou lab in March 2024. Welcome Yongji!
Weilan will be taking good care of the Zhou lab starting from February 2024. Thank you Weilan and welcome!
Bryan Chacon Vazquez joined the Zhou lab in February 2024. Welcome Bryan!
The Zhou lab at Emory University School of Medicine opens in January 2024!
We are hiring at all levels!
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