Skip Navigation

COVID-19: We are vaccinating patients ages 12+. Learn more:

Vaccines & 3rd Doses | Testing | Patient Care | Visitor Guidelines | Coronavirus | Self-Checker | Email Alerts

 

Philips Respironics issued a recall for some CPAP and BiLevel PAP devices and mechanical ventilators. Learn more.

Background

Dr. Xiaobo Mao focuses on protein aggregation and prion-like spreading that drive the pathogenesis in neurodegenerative disorders, including Alzheimer's disease and Lewy Body Dementia. He pioneered the role of the receptors of prion-like proteins (tau and α-synuclein), including lymphocyte-activation gene 3 (LAG3), amyloid-β precursor-like protein 1 (APLP1), and neurexins, in mediating prion-like proteins cell-to-cell transmission and neuroinflammation. He and his collaborators identified the importance of the C-terminus of α-synuclein and serine129 phosphorylated α-synuclein binding to its receptors (LAG3 and APLP1), and the complex of APLP1-LAG3, exacerbating pathology spread and neurodegeneration. He co-discovered the targets of poly (ADP-ribose) polymerase (PARP) and PAR polymer facilitating prion-like protein spreading and neurodegeneration. He is also determining the role of pathogenic α-synuclein with different aggregation confirmation (strains) driving disease-specific α-synucleinopathies, including the underlying mechanism induced by environmental factors, and the association with clinical features.

Dr. Xiaobo Mao received his Ph.D. in Physical Chemistry from the National Center for Nanoscience and Technology, Chinese Academy of Sciences, China. He then came to Johns Hopkins where he completed a postdoc fellowship and Assistant Professor in Neurology, Institute for Cell Engineering. 

...read more

Titles

  • Associate Professor of Neurology

Departments / Divisions

Education

Degrees

  • Ph.D.; National Center for Nanoscience and Technology (China) (2010)

Research & Publications

Research Summary

I received my scientific training in the field of neurodegeneration and protein science. My laboratory has been at the forefront of exploring the role of prion-like proteins in the pathogenesis of neurodegeneration, including protein misfolding strains and structures, pathology spread, neurotoxicity, and neuroinflammation. We have pioneered the understanding of the cell-to-cell transmission of pathogenic α-syn, learning that lymphocyte-activation gene 3 (LAG3) is an essential receptor that mediates the internalization of α-syn preformed fibrils (PFF) (Science 2016). Deletion and inhibition of LAG3 significantly impede α-syn pathology spread. This work is selected as one of the 40 key discoveries in 200-years Parkinson’s disease basic research. We have identified amyloid-β precursor-like protein 1 (APLP1) as a LAG3 co-receptor that facilitates the neuronal uptake of α-syn PFF, and we have provided the mechanistic understanding on the spread of pathological proteins and provides structural information for the therapeutic targeting of pathological α-syn spread (PNAS 2021). Internalized PFF further induces the activation of poly (ADP-ribose) polymerase 1 (PARP1) and PAR accumulation, converting α-syn into a highly toxic strain (PAR-PFF). Both depletion and inhibition of PARP1 significantly inhibit PFF-induced neurodegeneration (Science 2018). We have studied the structures of misfolded protein/peptide and identified the amino acid sequence and core-β-sheet hairpin domains by biophysical method (JACS 2013; PNAS 2011). My laboratory employs advanced technologies, including a prion-like spread model, high-throughput screening platforms, protein misfolding cyclic amplification, nanobody, PROTAC, nanomaterials (Nano Today 2021), compound and protein microarray, to explore new molecular mechanisms and identify new agents to prevent aging-related pathogenesis.

Lab

Lab Website: Xiaobo Mao

Technology Expertise Keywords

Cell and Protein Biology, Biophysics

Selected Publications

Mao X, Ou MT, Karuppagounder SS, Kam TI, Yin X, Xiong Y, Ge P, Umanah GE, Brahmachari S, Shin JH, Kang HC, Zhang J, Xu J, Chen R, Park H, Andrabi SA, Kang SU, Goncalves RA, Liang Y, Zhang S, Qi C, Lam S, Keiler JA, Tyson J, Kim D, Panicker N, Yun SP, Workman CJ, Vignali DA, Dawson VL, Ko HS, Dawson TM. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science. 2016 Sep 30;353(6307).

Kam TI#, Mao X#, Park H# (# equal contribution), Chou SC, Karuppagounder SS, Umanah GE, Yun SP, Brahmachari S, Panicker N, Chen R, Andrabi SA, Qi C, Poirier GG, Pletnikova O, Troncoso JC, Bekris LM, Leverenz JB, Pantelyat A, Ko HS, Rosenthal LS, Dawson TM and Dawson VL. Poly (ADP-ribose) Drives Pathologic α-Synuclein Neurodegeneration in Parkinson’s Disease. Science. 2018;362(6414). doi: 10.1126/science.aat8407.

Mao X, Guo Y, Luo Y, Niu L, Liu L, Ma X, Wang H, Yang Y, Wei G, Wang C. Sequence effects on peptide assembly characteristics observed by using scanning tunneling microscopy. J Am Chem Soc. 2013 Feb 13;135(6):2181-7. 

Liu YQ, Mao YY (co-first), Xu EQ, Jia HM, Zhang S, Dawson VL, Dawson TM, Li YM*, Zheng Z*, He WW*, Mao X*. Nanozyme Scavenging ROS for Prevention of Pathologic α-Synuclein Transmission in Parkinson’s Disease. Nano Today. 2021, 36, 101027

Zhang SN, Liu YQ, Jia CY, Lim YJ (co-first), Feng GQ, Xu EQ, Kimura Y, Long HF, Tao YQ, Zhao CY, Wang CC, Liu ZY, Hu JJ, Ma MR, Liu ZJ, Jiang L, Li D, Wang RX, Dawson VL, Dawson TM*, Li YM*, Mao X*, Liu C*. Mechanistic basis for receptor-mediated pathological α-synuclein fibril cell-to-cell transmission in Parkinson's disease. Proc Natl Acad Sci. USA. 2021;118(26): e2011196118

Patents

A detection method for the relative adsorption constant of dye, antibody, drug and pro-drug molecules on peptides.
Patent # WO2011060598A1 & CN102062718 | 

Therapeutic Uses of LAG3 the α-Synuclein Transmission Receptor.
Patent # WO2018039147A1, PCT/US2017/047878 | 

Nanozyme Scavenging ROS for Prevention of Pathologic α-Synuclein Transmission in Parkinson’s Disease
Patent # C16214 | 

Contact for Research Inquiries

Xiaobo Mao
733 N. Broadway, MRB 715
Baltimore, MD 21205 map

Email me

Academic Affiliations & Courses

Courses and Syllabi

  • Parkinson’s Disease and Disease-Modifying Therapy---STEM CELLS AND THE BIOLOGY OF AGING AND DISEASE (AS.020.337)

Activities & Honors

Honors

  • Outstanding Student Award, National Center for Nanoscience and Technology (China), 2007
  • Director's Scholarship, National Center for Nanoscience and Technology (China), 2007
  • NIA/ADRC Johns Hopkins Pilot Project Awards, NIA/ADRC, 2016
  • 18th Annual NINDS Udall Centers Meeting, the Best Poster Awards, NINDS Udall Centers Meeting, 2016
  • the Paul Ehrlich Research Awards, the Johns Hopkins University Young Investigator's Day, 2017
  • APDA Research Grant, APDA, 2017
  • New Investigator Awards in Alzheimer's Disease, AFAR, the Rosalinde and Arthur Gilbert Foundation, 2018
  • CurePSP Grant Award, CurePSP Foundation, 2018
  • Stanley Fahn Junior Faculty Award, Parkinson's foundation, 2019
  • Discovery Award, Maryland Stem Cell Research Fund, 2019

Memberships

  • American Chemical Society
  • Society for Neuroscience
  • International Society for Neurochemistry
  • The Gerontological Society

Professional Activities

  • Guest Associate Co-Editor, Frontier in Neurology, 2018
  • Guest Associate Co-Editor, Frontier in Cellular Neuroscience, 2019
  • Guest Associate Co-Editor, Frontier in Aging Neuroscience, 2019

Videos & Media

Recent News Articles and Media Coverage

Artificial enzyme may be first step toward treatment for Parkinson's disease, Johns Hopkins Institute for Clinical and Translational Research (ICTR)January 19, 2021

Xiaobo Mao: Paul Ehrlich Award, Johns Hopkins Medicine

Is this you? Edit Profile
back to top button