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Wei-Bin Shen, PhD

Academic Title:

Associate Professor

Primary Appointment:

Obstetrics, Gynecology and Reproductive Sciences

Email:

wbshen@som.umaryland.edu

Location:

655 West Baltimore Street

Phone (Primary):

410-706-1097

Fax:

410-706-5747

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Education and Training

1983 – BSc, Department of Biology, Hangzhou University, China. Majoring in Biology

1987 – MSc, Reproductive Physiology, Institute of Zoology, Chinese Academy of Sciences.  Thesis Title: Opioid peptides participate the negative feedback regulation of sex steroid hormone on hypothalamic GnRH secretion

1995 – PhD, Neuroendocrinology, State Key Laboratory of Reproductive Biology, Chinese Academy of Sciences, Beijing, China. Thesis Title: Regulation of adrenergic system and opioid peptides on hypothalamic GnRH secretion

Biosketch

I was trained in brain development and molecular neuroscience. I had worked for more than 14 years on neurodegenerative diseases and demonstrated that Cycad neurotoxins cause a-synuclein deposits in the brain regions in which synucleinopathy has been observed in patients with Parkinson’s disease, and induces behavioral disorders similar to that of early PD. By using a non-invasive surgery procedure, I had delivered iron-nanoparticle-labeled neural stem cells to the brain in the traumatic brain injury model and found that an external magnet enhances the retention of nanoparticle-labeled stem cells. 

I joined Dr. Peixin Yang’s team in the Center for Birth Defects Research eight years ago to work on embryonic development, especially the roles of cellular stress, signaling transduction impact, and epigenetic dysregulation in maternal-diabetes-induced birth defects. Working in the Center, I have tremendously benefited by the team science approach and demonstrated that (a) high glucose suppresses embryonic stem cell differentiation into neural lineage leading to impaired neurogenesis and subsequent failed neural tube closure, (b) high glucose triggers cardiac progenitor apoptosis during embryonic heart development resulting in congenital heart defects, (c) p70S6K1, a mTORC1 downstream mediator, is critically involved in the pathogenesis of diabetic embryopathy, (d) epigenetic dysregulation and impaired neuronal insulin receptor signaling precedes overt AD neuropathology. I have successfully competed with other investigators and received a department research development grant in obesity-induced placental maldevelopment.

I have been serving as a co-investigator in completed NIH R01s, and MPI or co-investigator in the several active R01s. I am a key member of the Center for Birth Defects Research. My experience in maternal diabetes-induced embryopathy and background in molecular and epigenetic neuroscience, technical skills, and my publication record indicate that I am qualified to conduct the projects to understand the mechanisms of maternal diabetes-induced embropathies.

Research/Clinical Keywords

neural tube defects, congenital heart defects, epigenetic regulation, cellular signaling, Stem cell differentiation, neurodegenerative diseases,

Highlighted Publications

  1. Wei-Bin Shen, Bingbing Wang, Ruofan Yao, Katherine R Goetzinger, Sheng Wu, Haijun Gao, and Peixin Yang. Obesity impacts placental function through activation of p-IRE1a-XBP1s signaling. Front Cell Dev Biol. 2023; 11:1023327. doi: 10.3389/fcell.2023.1023327.
  2. Wei-Bin Shen, Montasir Elahi, James Logue, Penghua Yang, Lauren Baracco, E Albert Reece, Bingbing Wang, Ling Li, Thomas G Blanchard, Zhe Han, Robert A Rissman, Matthew B Frieman, Peixin Yang. SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer's-like neuropathology. bioRxiv. 2022 Sep 6; doi: 10.1101/2022.01.31.478476. PubMed PMID: 35132414
  3. Shen WB, Elahi M, Wang B, Zhang M, Yang P, Yang P. Oxidative stress kinase activation and impaired insulin receptor signaling precede overt Alzheimer's disease neuropathology. Journal of Alzheimer’s Disease, 2022, 90(2):841-857. doi: 10.3233/JAD-215687.
  4. Cheng Xu, Wei-Bin Shen, E. Albert Reece, Hidetoshi Hasuwa, Christopher Harman, Sunjay Kaushal, Peixin Yang. Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic Rapamycin. Sciences Advances 2021, 30;7(27):eabf5089. doi: 10.1126/sciadv.abf5089
  5. Songying Cao, Wei-Bin Shen, E. Albert Reece, Peixin Yang. Deficiency of the oxidative stress-responsive kinase p70S6K1 restores autophagy and ameliorates neural tube defects in diabetic embryopathy. Am J Obstet Gynecol 2020, 1.e1-e11; S0002-9378(20)30540-8.doi: 10.1016/j.ajog.2020.05.015

Additional Publication Citations

  1. Bingbing Wang, Wei-Bin Shen, Peixin Yang, and Sifa Turan. SARS-CoV-2 infection induces activation of ferroptosis in human placenta. Front Cell Dev Biol 2022; 10:1022747. doi: 10.3389/fcell.2022.1022747
  2. Wei-Bin Shen, James Jiao Yang, Peixin Yang. RNA Hypomethylation and Unchanged DNA Methylation Levels in the Cortex of ApoE4 Carriers and Alzheimer's Disease Subjects. Curr Alzheimer Res. 2022;19(7):530-540. doi: 10.2174/1567205019666220831125142.
  3. Songying Cao, Yanqing Wu, Albert Reece, Cheng Xu, Shen W-B, E. Sunjay Kaushal, Peixin Yang. Functional cargos of exosomes derived from Flk-1+ vascular progenitors enable neurulation and ameliorate embryonic anomalies in diabetic pregnancy. Communications Biology 2022, 5:648.
  4. Ruofan Yao, Penghua Yang, Katherine R Goetzinger, Kristin L Atkins, Wei-Bin Shen, Bingbing Wang, Peixin Yang, Maternal obesity-associated disruption of polarized lactate transporter MCT4 expression in human placenta. Reproductive Toxicology 2022, 112:1-6
  5. Wei-Bin Shen, Shifa Turan, Bingbing Wang, Liviu Cojocaru, Christopher Harman, James Logue, E. Albert Reece1, Matthew B Frieman, Peixin Yang. A SARS-CoV-2 Delta Variant Case Manifesting as Extensive Placental Infection and Fetal Transmission. A Case Report, Obstetrics & Gynecology Investigation 2022, 87(2):165-172
  6. Wei-Bin Shen, Jingxiang Ni, Penghua Yang, Ruofan Yao, Katherine R Goetzinger, Christopher Harman, E. Albert Reece, Bingbing Wang, Peixin Yang. Maternal obesity increases DNA methylation and decreases RNA methylation in the human placenta. Reproductive Toxicology 2022, 107:90-96
  7. Cheng Xu, Shen W-B, E. Albert Reece, Hidetoshi Hasuwa, Christopher Harman, Sunjay Kaushal, Peixin Yang. Maternal diabetes induces senescence and neural tube defects sensitive to the senomorphic rapamycin. EMBO Molecular Medicine 2020, EMM-2020-13472. BioRxiv 2020, doi: https://doi.org/10.1101/2020.09.18.303222
  8. Songying Cao, E. Albert Reece, Wei-Bin Shen, Peixin Yang. Restoring BMP4 expression in vascular endothelial progenitors ameliorates maternal diabetes-induced apoptosis and neural tube defects. Cell Death Disease 2020, 11(10):859. doi: 10.1038/s41419-020-03078-5
  9. Xu C, Chen X, Shen WB, Yang P. Trehalose restores functional autophagy suppressed by high glucose. Reprod Toxicol. 2019, 85:51-58.
  10. Chen X, Shen W-B, Yang P, Dong D, Sun W, Yang P. High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress. Stem Cells Dev 2018, 27(11):745-755
  11. Zhong J, Wang S, Shen W-B, Kaushal S, Yang P. The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy. Pediatric Res 2018; 83:275-282
  12. Shen W-B, Anastasiadis P, Nguyen B, Yarnell D, Yarowsky P, Frenkel V, Fishman PS. Magnetic Enhancement of Stem Cell-Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood-Brain Barrier. Cell Transplant. 2017; 26(7):1235-1246
  13. Yang P, Yang WW, Chen X, Kaushal S, Dong D, Shen W-B*. Maternal diabetes and high glucose in vitro trigger Sca1+ cardiac progenitor cell apoptosis through FoxO3a. BBRC 2017; 482:575-582. *: Corresponding author
  14. Wu Y, Reece EA, Zhong J, Dong D, Shen WB, Harman CR, Yang P. Type 2 diabetes mellitus induces congenital heart defects in murine embryos by increasing oxidative stress, endoplasmic reticulum stress and apoptosis. Am J Obstet Gynecol, 2016, 215(3):336e1-366
  15. Shen W-B, Plachez C. Tsymbalyuk O, Tsymbalyuk N, Xu S, Smith AM, Michel SL, Yarnell D, Mullins R, Gullapalli RP, Puche A, Simard JM, Fishman PS, Yarowsky P. Cell-based therapy in TBI: Magnetic retention of neural stem cells in vivo. Cell Transplantation, 2016; 25(6):1085-1099
  16. Yang P, Shen WB, Reece EA, Chen X, Yang P. High glucose suppresses embryonic stem cell differentiation into neural lineage cells. BBRC 2016; 472:306-312
  17. Shen WB, Vaccaro DE, Fishman PS, Groman EV, Yarowsky P. SIRB, sans iron oxide rhodamine B, a novel cross-linked dextran nanoparticle, labels human neuroprogenitor and SH-SY5Y neuroblastoma cells and serves as a USPIO cell labeling control. Contrast Media Mol Imaging 2016, 11(3):222-228. doi: 10.1002/cmmi.1684.
  18. Shen W-B, Plachez C, Chan A, Puche A, Fishman PS, Yarowsky PJ. Human neural progenitor cells retain viability, proliferation, lineage differentiation, and migratory capability when labeled with novel iron oxide nanoparticle, Molday ION Rhodamine-B. Intl J Nanomed 2013, 8:4593-4600
  19. *Messmer K, *Shen W-B, Remington M, Fishman PS. Induction of neural differentiation by transcription factor neuroD2. J. Dev Neuroscience 2012, 30:105-112. *:Contribute equally
  20. McDowell KA, Shen W-B, Siebert AA, Sarah MC, Jinnah H, Sztalryd C, Fishman PS, Shaw CA, Jafri MS, Yarowsky PJ. Washed cycad flour contains β-N-methyl amino-L-alanine and may explain parkinsonism symptoms. Ann Neurol 2011, 69(2):423-424.
  21. Shen WB, McDowell KA,Siebert AA, Clark SM, Dugger NV, Valentino KM, Jinnah HA, Sztalryd C, Fishman PS, Shaw CA, Jafri MS, Yarowsky PJ. Environmental neurotoxin-induced progressive model of parkinsonism in rats. Annual Neurol 2010, 67(5):1-11
  22. Ren T, Anderson A, Shen WB, Huang H, Plachez C, Zhang J, Mori S, Kinsman SL, Richards LJ. Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain. Anat Rec ADiscovMol Cell Evol Biol. 2006, 288:191-204
  23. Shen WB, Plachez C, Mongi AS, Richards LJ. Identification of novel genes at the corticoseptal boundary during development. Gene Expression Patterns 2006, 6:471-481
  24. Al-Damluji S, Shen WB, White S, Barnard EA. α1B adrenergic receptor in gonadotrophin releasing hormone neurons: relation to Transport P. Br J Pharmacol 2001, 132:336-344
  25. Al-Damluji S, Shen WB. Release of amines from acidified stores following accumulation by Transport P. Br J Pharmacol 2001, 132:851-860
  26. Shu T, Shen WB, Richards RJ. Development of the perforating pathway: an ipsilaterally projecting pathway between the medial septum/diagonal band of Broca and the cingulate cortex that intersects the corpus callosum. J Comp Neurobiol 2001, 6:411-422
  27. Searles RV, Yoo MJ, He JR, Shen WB, Selmanoff M. Sex differences in GABA turnover and glutamic acid decarboxylase (GAD65 and GAD67) mRNA in the rat hypothalamus. Brain Res 2000, 878:11-19.
  28. Yoo MJ, Searles RV, He JR, Shen WB, Grattan DR, Selmanoff M. Castration rapidly decreases hypothalamic gamma aminobutyric acidergic neuronal activity in both male and female rats. Brain Res 2000, 878:1-10.
  29. Shen WB. Catecholamine regulation of hypothalamic gonadotropin-releasing hormone. Sheng Li Ko Hsueh Chin Chan (Prog Physiol Sci) 1996, 27:368-370
  30. Tang MY, Shen WB, Zhang CL. Establishment of radioimmunoassay for corticotrophin-releasing hormone. Chinese J Appl Physiol 1995, 11:284-287
  31. Yin H, Zhang CL, Wang H, Shen WB. Studies on amphioxus gonadotropin-releasing hormone (GnRH) during breeding season. Acta Zoologica Sinica 1994, 40:63-68
  32. Zhang CL, Cheng LR, Shen WB, Yin H, Huang WQ. Existence and functions of neurotensin in human early placental villi. Devel Reprod Biol 1994, 3:25-33
  33. Zhang CL, Yin H, Shen WB, Wang H. Two different forms of gonadotropin-releasing hormone in amphioxus. Devel Reprod Biol 1993, 2:33-37
  34. Huang QH, Cai YP, Zhang CL, Shen WB. Effects of intraventricular injection of 6-hydroxydopamine on the levels of monoamine and β-endorphin in brain and serum TSH in the ground squirrel. Acta Zoologica Sinica 1993, 39:169-175
  35. Zhang CL, Cheng LR, Yin H, Shen WB, Huang WQ. Luteinizing hormone-releasing hormone in human early placental villi. Contraception 1992, 46:159-160
  36. Zhang CL, Yin H, Wang H, Jiao LH, Shen WB. Profile of neurotransmitters during the period of spawning/spermiation in amphioxus. Chinese Sci Bull 1991, 36:695-696
  37. Shen WB, Yin H, Wang H, Zhang CL. Opioid peptides in amphioxus during the breeding season. Chinese Sci Bull 1991, 36:1481-1484
  38. Huang WQ, Shen WB, Zhang CL. Distribution of β-endorphin in the gonad of amphioxus, In Annual Report of Experimental Oceanographic Biology Laboratory (Chinese Academy of Sciences), 1990, pp. 9-11
  39. Shen WB, Zhang CL. Opioid peptides and reproduction in amphioxus, In Annual Report of Experimental Oceanographic Biology Laboratory (Chinese Acad of Sciences), 1990, pp. 1-8
  40. Shen WB, Wang H, Zhang CL. Participation of β-endorphin in the negative feedback regulation of estrogen. Acta Zoologia Sinica 1990, 36:286-292

Research Interests

My research interests focus on stem cell therapy on neural tube defects, congenital heart defects and neurodegenerative diseases,  and intracellular signaling pathways that lead the birth defects.

Grants and Contracts

R01 HD108705, MPI: Peixin Yang and Wei-Bin Shen.  Intersection of the mTOR/p70S6K1 signaling and the HIPPO-Yap tissue organizer in neurulation and diabetic embryopathy.  12/21/2022 – 11/30/2027; Role: MPI

R01 HL160727, MPI: Peixin Yang, Shifa Turan, and Wei-Bin Shen.  Heightened hypoxia and DNA methylation in heart defects of diabetic embryopathy.  9/15/2022 – 7/30/2026; Role: MPI

1R01 HD099843, MPIs:  EA Reece, W-B Shen, and P Yang. Epitranscriptomic alteration and planar cell polarity signaling in diabetic embryopathy.  9/21/2020 – 7/31/2025; Role: MPI

1R01HL153141, MPI: P Yang and EA Reece. Hyperglycemia of maternal diabetes induces cardiac Isl1 positive progenitor dysfunction leading to heart defects. 7/1/2020 – 06/30/2025; Role: Co-Inv

R01 HD100195,  MPI: P Yang and EA Reece. Molecular signaling pathways and cellular stress in diabetic embryopathy. 7/1/2019 – 6/30/2024. Role: Co-Inv

Lab Techniques and Equipment

Stem cell research

  • Mouse embryonic stem cells, human neural progenitor cells and amniotic fluid stem cells
  • Stem cell differentiation in vitro

 Animal models for exploring therapeutic intervention for diseases

  • Mouse colony maintenance, breeding, genotyping, sampling

Molecular biology

  • PCRs (including real-time PCR), DNA cloning and subcloning
  • Southern/Northern blot and Western blot, immunoprecipitation
  • CRISPR to knockout and siRNA to knock down gene expression

Pathology analysis of tissues

  • Sectioning (vibrotome and cryostat sectioning)
  • Histology staining (e.g. HE staining)
  • Immunohistology and immunofluuorescence labeling
  • Microscopy (Confocal, bright field, and fluorescent microscopy)

Computer skills:

  • Microsoft Windows and office
  • Image processing, densitometry analysis, and graphing: photoshop, GraphPad Prism, Zeiss Axiovision, Nikon NIS-Element
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