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| Huaibin Cai, Ph.D., Investigator |
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Dr. Huaibin Cai received his B.S. degree in 1991 from Peking University, Beijing, China, and his Ph.D. degree in 1999 from the Johns Hopkins University School of Medicine. His graduate studies in the laboratory of Dr. Randy Reed focused on the transcriptional regulation of olfactory receptors 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, where his laboratory investigates the pathogenic mechanisms of neurodegenerative diseases.
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Staff:
- Jayanth Chandran, M.S., Predoctoral Fellow, (301) 451-2119 chandrj@mail.nih.gov
- Lai Chen, Ph.D., Postdoctoral Fellow, (301) 451-3823 laichi@mail.nih.gov
- Shimoji Mika , Ph.D., Postdoctoral Fellow, (301) 435-8823 shimojim@mail.nih.gov
- Hoon Shim, M.S., Biologist, (301) 451-3825 shimh@mail.nih.gov
- Lizhen Wang, Ph.D., Postdoctoral Fellow, (301) 435-3823 wangli@mail.nih.gov
- Chengsong Xie, Ph.D., Biologist, (301) 435-8664 xiech@mail.nih.gov
- Lin Xin, Ph.D., Postdoctoral Fellow, (301) 451-3823 linxi@mail.nih.gov
Research Interests:
My section focuses on studying the pathogenic mechanisms and experimental therapeutics of three major neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS).
AD is the most common neurodegenerative disease. Excessive accumulation of amyloid beta (A-beta) peptides in the brain contributes to the pathogenesis of AD. A-beta is derived from amyloid precursor protein by endoproteolytic cleavages of BACE1 and gamma-secretase. We along with others have established that BACE1 is responsible for the generation of A-beta. Most recently, we have demonstrated that inhibition of BACE1 completely prevents the formation of A-beta deposition and fully rescues the cognitive impairments in an AD mouse model, which strongly argues that BACE1 is a high priority therapeutic target for AD. However, even though the BACE1 knockout mice are viable and show no major pathological abnormalities, they do display subtle changes in emotional behaviors. To better understand the biological functions of BACE1, we are now interested in identifying new substrates of this aspartyl protease. In addition, we are also engaged in screening regulatory elements that control the stability and activity of BACE1 for potential therapeutic applications.
PD is the second most common neurodegenerative disease. Recently, three more PD-related genes, including DJ-1, PINK1, and Dardarin have been identified, which when mutated cause familial PD. Currently, we are aimed to define the molecular pathways mediated by these three proteins in which their mutations inevitably cause the death or malfunction of the dopaminergic neurons in the brain. Besides AD and PD, we are also interested in the pathogenesis of ALS, the most common motor neuron diseases. We are studying mutations in ALS2 and dynactin, which contribute to the selective loss of motor neurons.
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Selected Recent Publications:
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.
Li T, Ma G, Cai H, Price DL, Wong PC (2003) Nicastrin is required for assembly of presenilin/��-secretase complexes to mediate Notch Signaling, and processing and trafficking of ��-APP in mammals, Journal of Neuroscience 23(8), 3272-3277.
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.
Wong PC, Price DL, and Cai H (2001) The brain's susceptibility to amyloid plaques, Science 293(5534), 1413.
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.
Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, and Wong PC (2001) BACE1 is the major �� - secretase required for generation of A�� peptides in neuron., Nature Neuroscience 4, 233-234.
All Selected Publications
Contact Information:
Dr. Huaibin Cai
Laboratory of Neurogenetics, NIA
Porter Neuroscience Research Center
35 Convent Dr, MSC 3707
Building 35, Room 1A116
Bethesda, MD 20892-3707
Telephone: (301) 402-8087 (office),
(301) 480-2830 (fax)
Email: caih@mail.nih.gov
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