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Senior Investigator

Huaibin Cai, Ph.D.

Laboratory of Neurogenetics

Porter Neuroscience Research Center
Building 35 Room 1A116
35 Convent Drive MSC3707
Bethesda MD 20892-3707
Office: (301) 402-8087

Fax: (301) 480-2830
caih@mail.nih.gov

Dr. Huaibin Cai received his B.S. degree from Peking University in 1991, and his Ph.D. degree in Neuroscience from the Johns Hopkins University School of Medicine in 1999. His graduate studies in the laboratory of Dr. Randy Reed focused on the transcriptional regulation of olfactory receptor gene expression and axonal path finding of olfactory sensory neurons. Dr. Cai then joined the laboratories of Drs. Don Price and Philip Wong in the Division of Neuropathlogy at Johns Hopkins University, initially as a postdoctoral research fellow and then as a research associate. His research at Johns Hopkins focused on the pathogenesis of Alzheimer's disease, with an emphasis on the role of BACE1 in the generation of disease causing amyloid-beta peptides. Dr. Cai joined the NIA as an Investigator in 2003, and was promoted to Senior Investigator in 2011. His laboratory investigates the molecular pathogenic mechanisms of neurodegenerative diseases.

The Transgenics Section (TS) in the Laboratory of Neurogenetics of NIA focuses on studying the pathobiological properties of genetic mutations associated with ALS and PD using a combination of in vivo mouse modeling and in vitro neurobiological approaches. While most of Parkinson's disease (PD) and ALS cases are sporadic, a small fraction is inherited. The specific genetic defects underlying the familial forms of diseases may provide valuable molecular handles for elucidating the pathogenic mechanisms of the diseases. Following this principle, we have generated a series of novel mouse genetic models for ALS and PD to investigate the pathophysiological phenotypes of various ALS and PD-related genetic mutations and test potential therapeutics. Currently, we focus our research on the functions and pathogenic mechanisms of alpha-synuclein and LRRK2 in PD, VAPB in ALS, and dynactin p150glued in Perry syndrome, a subtype of PD with severe mental depression. We are actively exploring the underlying molecular and cellular mechanisms of these genetic mutations in brain sections and primary neuronal cultures using a variety of histology, electrophysiology, cell biology and biochemistry approaches. Meanwhile, we also take advantage of newly developed microarray and direct RNA sequencing techniques to systematically identify molecular networks critical for the degeneration of midbrain dopaminergic neurons and motor neurons. One such example is microarray analysis of mRNA isolated from laser captured dopaminergic neurons of alpha-synuclein and LRRK2 transgenic mice and search for the dopaminergic neuron-specific gene expression alterations induced by exogenous expression of PD-related mutant alpha-synuclein and LRRK2.We expect this highly integrated interdisciplinary research strategy may bring new insights into the pathogenic mechanisms of ALS and PD, while also providing new biomarkers and therapeutic targets for diagnosis and treatment of these devastating illnesses.
Staff Image

  • Lisa Chang
    Biologist

  • Xi Chen, Ph.D.
    Visiting Fellow

  • Namratha Sastry
    IRTA

  • Carmelo Sgobio, Ph.D.
    Visiting Fellow

  • Lixin Sun, Ph.D.
    Biologist
    (301) 435-8866

  • Junbing Wu, Ph.D.
    Visiting Fellow

  • Chengsong Xie, Ph.D.
    Biologist
    (301) 435-8664

  • Jia Yu, M.D., Ph.D.
    Visiting Fellow

  • Wang Zheng, Ph.D.
    Visiting Fellow

  • 1) Parisiadou L, Yu J, Sgobio C, Xie C, Liu G, Sun L, Gu XL, Lin X, Crowley NA, Lovinger DM, Cai H. (2014)
    •
  • LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity.
  • Nat Neurosci.
  • 2) Liu G, Yu J, Ding J, Xie C, Sun L, Rudenko I, Zheng W, Sastry N, Luo J, Rudow G, Troncoso JC, Cai H. (2014)
    •
  • Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation.
  • J Clin Invest.
  • 3) Aliaga L, Lai C, Yu J, Chub N, Shim H, Sun L, Xie C, Yang WJ, Lin X, O'Donovan MJ, Cai H. (2013)
    •
  • Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially affects the function and survival of corticospinal and spinal motor neurons.
  • Hum Mol Genet.
  • 4) Jo DG, Arumugam TV, Woo HN, Park JS, Tang SC, Mughal M, Hyun DH, Park JH, Choi YH, Gwon AR, Camandola S, Cheng A, Cai H, Song W, Markesbery WR, Mattson MP. (2010)
    •
  • Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer's disease.
  • Neurobiol Aging. , Jun;31(6):, 917-25.
  • 5) Zhang XM, Xiong K, Cai Y, Cai H, Luo XG, Feng JC, Clough RW, Patrylo PR, Struble RG, Yan XX. (2010)
    •
  • Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex.
  • Eur J Neurosci., Feb;31(4), 710-21.
  • 6) Parisiadou L, Cai H. (2010)
    •
  • LRRK2 function on actin and microtubule dynamics in Parkinson disease.
  • Commun Integr Biol., Sep;3(5), 396-400
  • 7) Yoo MH, Gu X, Xu XM, Kim JY, Carlson BA, Patterson AD, Cai H, Gladyshev VN, Hatfield DL. (2010)
    •
  • Delineating the role of glutathione peroxidase 4 in protecting cells against lipid hydroperoxide damage and in Alzheimer's disease.
  • Antioxid Redox Signal., Apr 1;12(7):, 819-27
  • 8) Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H. (2010)
    •
  • Astrocytic expression of Parkinson's disease-related A53T alpha-synuclein causes neurodegeneration in mice.
  • Mol Brain., Apr 21;, 3:12.
  • 9) Cai Y, Xiong K, Zhang XM, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Chu Y, Kordower JH, Yan XX. (2010)
    •
  • β-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and β-amyloid accumulation.
  • Eur J Neurosci., Oct;32(7):, 1223-38.
  • 10) Parisiadou L, Xie C, Cho HJ, Lin X, Gu XL, Long CX, Lobbestael E, Baekelandt V, Taymans JM, Sun L, Cai H (2009)
    •
  • Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis
  • J Neurosci. 2009 Nov 4; 29(44):13971-80
  • 11) Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L, Xie C, Long CL, Yang WJ, Ding J, Chen ZZ, Gallant PE, Tao-Cheng JW, Rudow G, Troncoso JC, Liu Z, Li Z, and Cai H (2009)
    •
  • Leucine-Rich Repeat Kinase 2 Regulates the Progression of Neuropathology Induced by Parkinson's Disease-related Mutant alpha-synuclein
  • Neuron 2009 Dec 24; , 64, 807-827
  • 12) Lai C, Xie C, Shim H, Chandran J, Howell BW, Cai H. (2009)
    •
  • Regulation of endosomal motility and degradation by amyotrophic lateral sclerosis 2/alsin.
  • Mol Brain. , Jul 24, 2:23.
  • 13) Zhang XM, Cai Y, Xiong K, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Yan XX. (2009)
    •
  • Beta-secretase-1 elevation in transgenic mouse models of Alzheimer's disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development.
  • Eur J Neurosci., Dec;30(12):, 2271-83
  • 14) Chandran JS, Lin X, Zapata A, Höke A, Shimoji M, Moore SO, Galloway MP, Laird FM, Wong PC, Price DL, Bailey KR, Crawley JN, Shippenberg T, Cai H. (2008)
    •
  • Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function.
  • Neurobiol Dis., Mar;29(3):, 505-14.
  • 15) Wang L, Shim H, Xie C, Cai H. (2008)
    •
  • Activation of protein kinase C modulates BACE1-mediated beta-secretase activity.
  • Neurobiol Aging., Mar;29(3):, 357-67
  • 16) Cai H, Shim H, Lai C, Xie C, Lin X, Yang WJ, Chandran J. (2008)
    •
  • ALS2/alsin knockout mice and motor neuron diseases.
  • Neurodegener Dis., 5(6), 359-66
  • 17) Wang Y, Chandran JS, Cai H, Mattson MP. (2008)
    •
  • DJ-1 is essential for long-term depression at hippocampal CA1 synapses.
  • Neuromolecular Med., 10(1):, 40-5
  • 18) van der Brug MP, Blackinton J, Chandran J, Hao LY, Lal A, Mazan-Mamczarz K, Martindale J, Xie C, Ahmad R, Thomas KJ, Beilina A, Gibbs JR, Ding J, Myers AJ, Zhan M, Cai H, Bonini NM, Gorospe M, Cookson MR. (2008)
    •
  • RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways.
  • Proc Natl Acad Sci U S A., Jul 22;105(29):, 10244-9.
  • 19) Wang L, Xie C, Greggio E, Parisiadou L, Shim H, Sun L, Chandran J, Lin X, Lai C, Yang W, Moore DJ, Dawson TM, Dawson VL, Chiosis G, Cookson MR, and Cai H (2008)
    •
  • The Chaperone Activity of Heat Shock Protein 90 is Critical for Maintaining the Stability of Leucine Rich Repeat Kinase 2
  • J Neurosci. 2008 March 26; 28(13): 3384-3391
  • 20) Lai C, Lin X, Chandran JS, Shim H, Yang W-J, and Cai H (2007)
    •
  • The G59S Mutation in P150glued Causes Dysfunction of Dynactin in Mice
  • J Neurosci. , Dec 19;27(51):, 13982-90. (a TWIJ article)
  • 21) Lin X, Shim H, Cai H. (2007)
    •
  • Deficiency in the ALS2 gene does not affect the motor neuron degeneration in SOD1(G93A) transgenic mice.
  • Neurobiol Aging. , Oct;28(10):, 1628-30.
  • 22) Erie EA, Shim H, Smith AL, Lin X, Keyvanfar K, Xie C, Chen J, Cai H. (2007)
    •
  • Mice deficient in the ALS2 gene exhibit lymphopenia and abnormal hematopietic function.
  • J Neuroimmunol., Jan;182(1-2):, 226-31
  • 23) van de Leemput J, Chandran J, Knight MA, Holtzclaw LA, Scholz S, Cookson MR, Houlden H, Gwinn-Hardy K, Fung HC, Lin X, Hernandez D, Simon-Sanchez J, Wood NW, Giunti P, Rafferty I, Hardy J, Storey E, Gardner RJ, Forrest SM, Fisher EM, Russell JT, Cai H, Singleton AB. (2007)
    •
  • Deletion at ITPR1 underlies ataxia in mice and spinocerebellar ataxia 15 in humans.
  • PLoS Genet. , Jun;3(6), e108
  • 24) Chandran J, Ding J, Cai H. (2007)
    •
  • Alsin and the molecular pathways of amyotrophic lateral sclerosis.
  • Mol Neurobiol. , Dec;36(3):, 224-31.
  • 25) Xiong K, Cai H, Luo XG, Struble RG, Clough RW, Yan XX. (2007)
    •
  • Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase (BACE1) proteins and activity in vivo in the rat retina.
  • Exp Brain Res. , Aug;181(3):, 435-46.
  • 26) Lai C, Xie C, McCormack SG, Chiang HC, Michalak MK, Lin X, Chandran JS, Shim H, Shimoji M, Cookson MR, Huganir RL, Rothstein JD, Price DL, Wong PC, Martin LJ, Zhu JJ, and Cai H (2006)
    •
  • Amyotrophic lateral sclerosis 2-deficiency leads to neuronal degeneration in amyotrophic lateral sclerosis through altered AMPA receptor trafficking
  • J Neurosci. 2006 Nov 8; 26 (45): 11798-806. (a TWIJ article)
  • 27) Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A. (2006)
    •
  • Genetics of Parkinson's disease and parkinsonism.
  • Ann Neurol. , Oct;60(4):, 389-98.
  • 28) Laird FM*, Cai H*, Savonenko AV*, Farah MH*, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, Borchelt DR, Price DL, Lee HK, Wong PC (2005)
    •
  • BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions
  • J Neurosci. 25(50): 11693-709. (*Equal Contribution)
  • 29) Cai H*, Lin X, Xie C, Laird FM, Lai C, Wen H, Chiang HC, Shim H, Farah MH, Hoke A, Price DL, Wong PC (2005)
    •
  • Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress
  • J Neurosci. 25 (33): 7567-74. (* Corresponding author)
  • 30) Li R, Lindholm K, Yang LB, Yue X, Citron M, Yan R, Beach T, Sue L, Sabbagh M, Cai H, Wong P, Price D, Shen Y (2004)
    •
  • Amyloid beta peptide load is correlated with increased beta-secretase activity in sporadic Alzheimer's disease patients.
  • Proc Natl Acad Sci U S A. , 101(10), 3632-7
  • 31) Wong PC, Cai H, Borchelt DR, Price DL. (2003)
    •
  • Alzheimer’s disease and motor neuron disease: The value of genetically engineered models.
  • Nature Neuroscience, 5(7), 633-639
  • 32) Li T, Ma G, Cai H, Price DL, Wong PC (2003)
    •
  • Nicastrin is required for assembly of presenilin/ƒ×-secretase complexes to mediate Notch Signaling, and processing and trafficking of ƒÒ-APP in mammals
  • Journal of Neuroscience , 23(8), 3272-3277
  • 33) Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, and Wong PC (2001)
    •
  • BACE1 is the major beta - secretase required for generation of A-beta peptides in neuron.
  • Nature Neuroscience , 4, 233-234
  • 34) Wong PC, Cai H, Borchelt DR, Price DL (2001)
    •
  • Genetically engineered models relevant to neurodegenerative disorders - Their value for understanding disease mechanisms and designing/testing experimental therapeutics.
  • Journal of Molecular Neuroscience, 17(2), 233-257
  • 35) Wong PC, Price DL, and Cai H (2001)
    •
  • The brain's susceptibility to amyloid plaques
  • Science , 293(5534), 1413
  • 36) Cai H and Reed RR (1999)
    •
  • Cloning and characterization of Neuropilin-1-Interacting protein: a PSD-95/Dlg/ZO-1 domain-containing protein that interacts with the cytoplasmic domain of Neuropilin-1
  • . Journal of Neurocience , 19, 6519-6527
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