Huaibin Cai, Ph.D.
Laboratory of Neurogenetics
Building 35, Room 1A112
35 Convent Drive
Bethesda, MD 20814
My lab focuses on studying the pathophysiological properties of genetic mutations associated with Parkinson's disease (PD) and ALS using a combination of in vivo mouse modeling and in vitro neurobiological approaches. While most of 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 PD and ALS to investigate the pathophysiological phenotypes of various PD and ALS-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 vivo and in primary neuronal cultures using a variety of histology, electrophysiology, cell biology and biochemistry approaches. Meanwhile, we also take advantage of newly developed RNA sequencing techniques to systematically identify molecular networks critical for the degeneration of nigrostriatal dopaminergic (DA) neurons.
In addition, we are keen to develop and utilize new optogenetics tools to map the basal ganglion DA circuits that are selectively affected in PD. In this regard, We are particularly interested in establishing the deep brain imaging system to study the neuron activity of basal ganglion DA circuits in PD-related mouse models. This new brain imaging approach may not only allow for early detection of disease-related preclinical alterations of DA transmission, but also for quick testing the efficacy of potential therapeutic interventions. We expect this highly integrated interdisciplinary research strategy may bring new insights into the pathogenic mechanisms of PD and ALS, while also providing new biomarkers and therapeutic targets for diagnosis and treatment of these devastating illnesses.
Dr. Huaibin Cai received his B.S. in Biology in 1991 from Peking University, Beijing, China and his Ph.D. in Neuroscience in 1999 from the Johns Hopkins University School of Medicine. He performed his postdoctoral training in the Division of Neuropathology, Department of Pathology at the Johns Hopkins University School of Medicine in Baltimore, Maryland. He joined the NIA Laboratory of Neurogenetics as an Investigator in 2003, and was promoted to Senior Investigator in 2011 to head the Transgenics Section.
Liu G, Yu J, Ding J, Xie C, Sun L, Rudenko I, Zheng W, Sastry N, Luo J, Rudow G, Troncoso JC, Cai H. Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation. J Clin Invest. 2014;124(7):3032-46.
Parisiadou L, Yu J, Sgobio C, Xie C, Liu G, Sun L, Gu XL, Lin X, Crowley NA, Lovinger DM, Cai H. LRRK2 regulates synaptogenesis and dopamine receptor activation through modulation of PKA activity. Nat Neurosci. 2014;17(3):367-76.
Cho HJ, Yu J, Xie C, Rudrabhatla P, Chen X, Wu J, Parisiadou L, Liu G, Sun L, Ma B, Ding J, Liu Z, Cai H. Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export. EMBO J. 2014;33(20):2314-31.
Lin X, Parisiadou L, Sgobio C, Liu G, Yu J, Sun L, Shim H, Gu XL, Luo J, Long CX, Ding J, Mateo Y, Sullivan PH, Wu LG, Goldstein DS, Lovinger D, Cai H. Conditional expression of Parkinson's disease-related mutant α-synuclein in the midbrain dopaminergic neurons causes progressive neurodegeneration and degradation of transcription factor nuclear receptor related 1. J Neurosci. 2012;32(27):9248-64.
Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L, Xie C, Long CX, Yang WJ, Ding J, Chen ZZ, Gallant PE, Tao-Cheng JH, Rudow G, Troncoso JC, Liu Z, Li Z, Cai H. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron. 2009;64(6):807-27.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on July 19th, 2018