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Yingwei Mao

Yingwei Mao

Main Content

Associate Professor of Biology

214 Life Sciences Building

University Park, PA 16802
Phone: (814)867-4739
Lab Address: 217 Life Sciences Building
Lab Phone: (814) 865-2762
Email:

Education

  1. B.S., Nankai University, 1996
  2. M.S. University of Medicine and Dentistry of New Jersey, 2002
  3. Ph.D., University of Michigan, 2005

Postdoc Training

  1. Harvard Medical School
  2. Massachusetts Institute of Technology

Honors and Awards

  1. Scientist Development Award, AHA, 2013
  2. Young Investigator Award, NARSAD, 2013
  3. Katowitz/Radin Investigator Award, NARSAD, 2008
  4. Young Investigator Award, NARSAD, 2007

Research Interests

The sophisticated human behaviors, such as language, tool use, and self awareness, require an extraordinary diversity of the neuronal population in the human brain. Such complexity results from neural stem/progenitor cells (NPCs) in the embryo with the ability to generate every cell type in the brain. The fundamental question in neurobiology is how NPCs self renew and give rise to enormously diverse neuronal cell types, which interconnect with amazing specificity to form functional neural circuits. Until recently, the functional relevance of disturbed neurogenesis to the pathophysiology of psychiatric disorders has just emerged. Schizophrenia is a severe psychiatric illness that affects 0.5-1 percent of the world population. Wile the etiology is poorly understood, emerging evidence hints that certain abnormal modifications in neurodevelopment may contribute to the etiology of psychiatric disorders.

The ultimate goal of our lab is to help develop better therapies and cures for mental illnesses. To achieve this, our lab focuses on understanding the mechanisms that lead to abnormal behaviors. In particular, we utilize cross-disciplinary techniques to overcome challenges that others have not been able to address. The research of our lab focuses on the mechanisms that regulate neurogenesis using mouse models and human stem cells. In the short term, we would like to focus our research program on determining how abnormal NPC proliferation and differentiation may lead to mental illnesses. Our long-term plan is to use the reagents, experimental systems, and mouse models that we develop to further screen novel drugs that can reverse the behavior phenotype in our mouse model and eventually benefit patients with psychiatric disorders.

Neural Progenitor Subtypes During Neurodevelopment
The cerebral cortex is the most complex brain structure within distinct subtypes of projection neurons located in six highly organized layers. We study the relationships among different NPCs and projection neuron subtypes and the genes that determine progenitor subtypes.

Genetic Mouse Models and iPS Model for Psychiatric Disorders
The neurodevelopmental hypothesis provides a promising approach to explore the pathogenesis of psychiatric disorders. By uncovering a new role for the schizophrenia candidate gene DISC1 in embryonic and adult neural progenitor proliferation, we connected NPC proliferation with schizophrenia (Cell 136: 1017). Our data suggest that decreased neural progenitor proliferation and defective differentiation may lead to psychiatric disorders.

Wnt Signaling Defect in Psychiatric Disorders
In parallel, we investigate whether other Wnt regulators modulate the neural stem cell proliferation and are involve in regulating mouse behavior. In the initial RNAi screen using a Wnt reporter assay, we identified multiple genes that modulate the strength of Wnt signaling, and some of them have been shown to be deleted in a genome-wide survey of rare copy number variants (CNVs) associated with schizophrenia. Thus, mouse models with different defects in Wnt signaling might be of great interest in relation to psychotic disorders. Using biochemical and cellular techniques, we will further investigate how these genes are involved in regulating Wnt signaling.

Development of Specific Inhibitor for Psychiatric Diseases
It is striking that many of the risk genes associated with schizophrenia directly or indirectly affect GSK3 regulatory pathways. Likewise, many drugs that modulate psychosis, including lithium and clozapine, alter GSK3 signaling. Some GSK3 inhibitors have been used for maintenance of embryonic stem cell self-renewal. Our results suggest that defects in neural stem cell proliferation may cause abnormal behaviors, which provides important insight into the pathophysiology of psychiatric disorders and offers potential avenues for therapeutic intervention. Our long-term goal is to develop specific GSK3 inhibitors that may maintain neural stem cell proliferation during psychiatric diseases, but do not interrupt other normal GSK3 functions. These inhibitors can be further validated using the patient-specific iPS cells and mouse models established in our lab.

Selected Publications

1.      Dong F, Xie K, Chen Y, Yang Y, Mao Y. Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells. 2017; Biochemical and Biophysical Research Communications.  482:889-895. 

2.      Zou D, Zhou Y, Liu L, Dong F, Shu T, Zhou Y, Tsai LH, Mao Y. Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice. 2016; Oncotarget. 7:39148-39161.

3.      Dong F, Jiang J, McSweeney C, Zou D, Liu L, Mao Y. Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects. 2016; Hum Mol Genet. 25:2738-2751.

4.      Boccitto M, Doshi S, Newton IP, Nathke I, Neve R, Dong F, Mao Y, Zhai J, Zhang L, Kalb R. Opposing actions of the synapse-associated protein of 97-kDa molecular weight (SAP97) and Disrupted in Schizophrenia 1 (DISC1) on Wnt/β-catenin signaling. 2016; Neuroscience. 326:22-30.

5.      Zou D, Chen L, Deng D, Jiang D, Dong F, McSweeney C, Zhou Y, Liu L, Chen G, Wu Y, Mao Y. DREADD in parvalbumin interneurons of the dentate gyrus modulates anxiety, social interaction and memory extinction. 2016; Curr Mol Med. 16:91-102.

6.      Zou D, McSweeney C, Sebastian A, Reynolds D, Dong F, Zhou Y, Deng D, Wang Y, Liu L, Zhu J, Zou J, Shi Y, Albert I, Mao Y. A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors. 2015, Neural Development. 10:18.

7.      Jiang H; Zou J; Wang B; Lin Y; Yu M; Pan Y; Li Y; Mao Y; Wang Y. The GluN2B subunit of N-methy-D-asparate receptor regulates the radial migration of cortical neurons in vivo. 2015; Brain Research. 1610:20-32.

8.      McSweeney C, Mao Y.  Applying stereotactic injection technique to study genetic effects on animal behaviors. 2015; JOVE (99), e52653, doi:10.3791/52653.

9.      Zhou M, Hao S, Cheng G, Yu X, Mao Y, and Zheng S. Integrated microdevice for single-neuron in vivo. 2014, The 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS 2014 preceding paper)

10.  Alachkar A, Jiang D, Harrison M, Zhou Y, Chen G, Mao Y.  An EJC Factor RBM8a Regulates Anxiety Behaviors. 2013; Curr Mol Med. 13:887-99.

11.  Liu J, Ji W, Sun S., Zhang L, Chen H-G, Mao Y, Liu L, Zhang X, Gong L, Deng M, Chen L, Han W-J, Chen P-C, Hu W-F, Hu X, Liu J, Woodward Z, Liu W-B, Xiao Y-M, Liang S-P, Liu Y, Liu S-J, and Li D.W-C The PP2A-α Gene is Regulated by Multiple Transcriptional Factors Including Ets-1, SP1/SP3, and RXR/β. 2012; Curr Mol Med. 12: 1-13.

12.  Singh K, Rienzo G, Drane L, Mao Y, Flood Z, Madison J, Fereira M, Bergen S, King C, Sklar P, Sive H, Tsai LH.  Common DISC1 polymorphisms disrupt Wnt/GSK3β-signaling and brain development. 2011; Neuron 72:545-58.

13.  Lee A W.-M., Mao Y, Penninger J, and Yu S. Gab2 promotes Colony Stimulating Factor-1 regulated macrophage expansion via alternate effectors at different stages of development. 2011; Mol Cell Biol. 31:4563-81.

14.  De Rienzo G, Bishop JA, Mao Y, Pan L, Ma T, Moens CB, Tsai LH, Sive H. DISC-1 regulates both β-catenin-mediated and non-canonical Wnt signaling during vertebrate embryogenesis. 2011; FASEB J. 25:4184-97.

15.  Gao J, Wang WY, Mao Y, Gräff J, Guan JS, Pan L, Mak G, Kim D, Su SC, Tsai LH. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. 2010; Nature. 466:1105-1109.

16.  Singh K, Ge X, Mao Y, Drane L, Meletis K, Samuels B, Tsai LH. Dixdc1 is a critical regulator of DISC1 and embryonic cortical development.  2010; Neuron. 67:33-48.

17.  Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK, Tassa C, Berry EM, Soda T, Singh KK, Biechele T, Petryshen TL, Moon RT, Haggarty SJ, Tsai LH. DISC1 regulates neural progenitor proliferation via modulation of GSK3β/β-catenin signaling. 2009; Cell. 136: 1017-1031. (cover)

18.  Yang P, Mao Y, Lee AW, Kennedy RT. Measurement of dissociation rate of biomolecular complexes using CE.  2009; Electrophoresis. 30:457-64.

19.  Yang PL, Whelan RJ, Mao Y, Lee AW.-M, Carter-Su C, and Kennedy RT. Multiplexed Detection of Protein-Peptide Interaction and Inhibition Using Capillary Electrophoresis. 2007; Anal. Chem., 79, 1690 -1695.

20.  Mao Y and Lee A W-M. A novel role of Gab2 in bFGF-mediated cell survival during retinoic acid-induced neuronal differentiation. 2005; J. Cell Biol. 170:305-16.

21.  Li DW, Liu JP, Mao Y, Xiang H, Wang J, Ma WY, Dong Z, Pike HM, Brown RE, Reed JC. Calcium-activated RAF/MEK/ERK Signaling Pathway Mediates p53-dependent Apoptosis and Is Abrogated by {alpha}B-Crystallin through Inhibition of RAS Activation. 2005; Mol Biol Cell. 16:4437-53.

22.  Wang J, Feng H, Huang XQ, Xiang H, Mao Y, Liu JP, Yan Q, Liu WB, Liu Y, Deng M, Gong L, Sun S, Luo C, Liu SJ, Zhang XJ, Liu Y, Li DW. hTERT immortalizes bovine lens epithelial cells and suppresses differentiation through regulation of the ERK signaling pathway. 2005; J Biol Chem. 280:22776-87.

23.  Mao Y, Liu JP, Xiang H, Li DW. Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. 2004; Cell Death Differ. 11:512-26.

24.  Feng H, Xiang H, Mao Y, Wang J, Liu JP, Huang XQ, Liu Y, Liu SJ, Luo C, Zhang XJ, Liu Y, Li DW. Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes. 2004; Oncogene. 23:7310-7321.

25.  Li DW, Liu JP, Wang J, Mao Y, Hou LH. Expression and activity of the signaling molecules for mitogen-activated protein kinase pathways in human, bovine, and rat lenses. 2003; Invest. Ophthalmol. Vis. Sci. 44:5277-5286.

26.  Xiang H, Wang J, Mao Y, Liu M, Reddy VN, Li DW. Human telomerase accelerates growth of lens epithelial cells through regulation of the genes mediating RB/E2F pathway. 2002; Oncogene. 21, 3784 –3791.

27.  Mao Y, Xiang H, Wang J, Korsmeyer S, Reddan J, Li DW. Human bcl-2 gene attenuates the ability of rabbit lens epithelial cells against H2O2-induced apoptosis through down-regulation of the aB-crystallin gene. 2001; J. Biol. Chem. 276: 43435-43445.

28.  Li DW, Xiang H, Mao Y, Wang J, Fass U, Zhang XY, Xu C. Caspase-3 is actively involved in okadaic acid-induced lens epithelial cell apoptosis. 2001; Exp. Cell. Res. 266: 279-291.

29.  Xiang H, Wang J, Mao Y, Li DW. hTERT can function with rabbit telomerase RNA: regulation of gene expression and attenuation of apoptosis. 2000; Biochem. Biophys. Res. Commun. 278: 503-510.

30.   Mao Y, Liang SY, Song WQ, Li XL, Chen RY. Construction of a DNA library from chromosome 4 of rice (Oryza sativa) by microdissection. 1998; Cell Res. 8:285-293.