Hung-Teh Kao Associate Professor of Psychiatry and Human Behavior (Research)

H.T. Kao received his M.D. from the University of Manitoba in Canada, his Ph.D. in molecular biology from the Rockefeller University, and psychiatry residency training at Stanford University. He joined Butler Hospital and the faculty at Brown University in 2007.

Brown Affiliations

scholarly work

Kao, H.-T., Li, P., Chao, H.M., Janoschka, S., Pham, K., Feng, J., McEwen, B.S., Greengard, P., Pieribone, V.A., Porton, B. (2008). Early involvement of Synapsin III in neural progenitor cell development in the adult hippocampus. J. Comp. Neurol. 507:1860-1870.

Kao, H.-T., Cawthon, R.M., DeLisi, L.E., Bertisch, H.C., Ji, F., Gordon, D., Li, P., Benedict, M.M., Greenberg, W.M., Porton, B. (2008). Rapid telomere erosion in schizophrenia. Mol. Psychiatry 13:118-119.

Kao, H.-T., Sturgis, S., DeSalle, R., Tsai, J., Davis, D.J., Gruber, D., and Pieribone, V.A. (2007) Dynamic regulation of fluorescent proteins from a single species of coral. Mar. Biotechnol. 9: 733-746.

Mei, J., Kolbin, D., Kao, H.-T., Porton, B. (2006). Protein expression profiling of postmortem brain in schizophrenia. Schizophrenia Res. 84: 204-213.

Bonanomi, D., Menegon, A., Miccio, A., Ferrari, G., Corradi, A., Kao, H.-T., Benfenati, F., Valtorta, F. (2005). Phosphorylation of synapsin I by cAMP-dependent protein kinase controls synaptic vesicle dynamics in developing neurons. J. Neurosci. 25: 7299-7308.

Gitler, D., Xu, Y., Kao, H.-T., Lin, D., Lim, S., Feng, J., Greengard, P., Augustine, G.J. (2004). Molecular determinants of synapsin targeting to presynaptic terminals. J. Neurosci. 24: 3711-3720.

Porton, B., Ferreira, A., DeLisi, L.E., Kao, H.-T. (2004). A rare polymorphism affects a MAP kinase site in synapsin III: Possible relationship to schizophrenia. Biol. Psychiatry 55: 118-125.

Pieribone, V.A., Porton, B., Rendon, B.E., Greengard, P., Kao, H.-T. (2002). Expression of Synapsin III in Nerve Terminals and Neurogenic Regions of the Adult Brain. J. Comp. Neurol. 454: 105-114.

Feng, F., Chi, P., Blenpied, T.A., Xu, Y., Magarinos, A.M., Ferreira, A., Takahashi, R., Kao, H.-T., McEwen, B.S., Augustine, G.J., Ryan, T.A., Greengard, P. (2002). Regulation of neurotransmitter release by synapsin III. J. Neurosci. 22: 4372–4380.

Kao, H.-T., Song, H.-j., Porton, B., Ming, G.-l., Abraham, M., Hoh, J., Czernik, A.J., Pieribone, V.A., Poo, M-m, Greengard P. (2002). A PKA-dependent molecular switch in synapsins regulates neurite outgrowth. Nature Neurosci. 5: 431-437.

Onofri, F., Giovedì, S., Kao, H.-T., Valtorta, F., Borbone, L.B., De Camilli, P., Greengard, P., Benfenati, F. (2000). Specificity of the binding of synapsin I to Src homology-3 domains. J. Biol. Chem. 275: 29857–29867.

Ferreira, A., Kao, H.-T., Feng, J., Rapoport, M., Greengard, P. (2000). Synapsin III: Developmental expression, subcellular localization, and role in axon formation. J. Neurosci. 20: 3736-3744.

Kao, H.-T., Porton, B., Hilfiker, S., Stefani, G., Pieribone, V.A., DeSalle, R., Greengard, P. (1999). Molecular evolution of the synapsin gene family. J. Exp. Zool. 285: 360-77.

Hilfiker, S., Schweizer, F.E., Kao, H.-T., Czernik, A.J., Greengard, P., and Augustine, G.J. (1998). Two sites of action for synapsin domain E in regulating neurotransmitter release. Nature Neurosci. 1: 29-35.

Kao, H.-T., Porton, B., Czernik, A.J., Feng, J., Yiu, G., Häring, M., Benfenati, F. , and Greengard, P. (1998). A third member of the synapsin gene family. Proc. Natl. Acad. Sci. USA 95: 4667-4672.

research overview

The mission of the Laboratory of Molecular Psychiatry is to investigate the molecular pathways that predispose individuals to neuropsychiatric diseases. A diverse range of experimental approaches is used, including molecular and cellular biology, proteomics and animal models.

research statement

The following summarizes the broad themes of this laboratory:
1. Molecular bases of major psychiatric disorders.
(a) Pathological aging in schizophrenia.
We recently observed that greater telomere shortening occurs in the peripheral blood lymphocytes of individuals with schizophrenia compared to controls. Telomeres, which are specialized DNA repeats located at the ends of chromosomes, progressively shorten with age. There is general agreement that increased telomere shortening in medical conditions is indicative of accelerated aging. These findings are consistent with clinical findings suggesting that rapid aging may be occurring in schizophrenia. Our laboratory is currently investigating the molecular bases and implications of these findings.
(b) Expression profiling in major psychiatric disorders.
The search for laboratory tests to establish the diagnosis of major psychiatric disorders has a long history spanning decades. The difficulties inherent in such a search include the challenges of psychiatric diagnoses, the limitations in examining the living brain non-invasively, and the subtlety of findings observed outside of the central nervous system. Nonetheless, advances are being made through the use of sensitive molecular techniques that delve into protein or gene expression profiles from a variety of tissues. We are currently using a proteomics approach to search for biomarkers to differentiate schizophrenia, bipolar disorder and individuals with no major psychiatric disorder.
(c) Is it possible to detect evidence of psychiatric dysfunction in experimental animals?
To advance research into psychiatric disorders it is desirable to have animal models, which have considerably advanced our knowledge in other fields of medicine. We are currently studying synapsin III knockout mice to examine behaviors linked to psychiatric disorders. Synapsin III is a presynaptic phosphoprotein that is a member of a family of presynaptic proteins known as synapsins. The rationale for examining this particular mouse is because levels of synapsin III have been shown to be decreased in the brains of individuals with schizophrenia, specifically in regions implicated in this disorder, such as the prefrontal cortex and hippocampus. Synapsins have also been implicated in the coordinate regulation of presynaptic protein levels, which as a group are downregulated in schizophrenia. Moreover, there is genetic evidence supporting a potential role for synapsin III in schizophrenia.
Among the current investigations that may have implications for psychiatric disorders are: (i) a functional polymorphism within the human synapsin III gene that occurs more frequently in individuals with schizophrenia compared to matched controls, and that disrupts MAP kinase signalling; (ii) regulation of adult neurogenesis by the synapsin III gene; and (iii) behaviors consistent with dopaminergic dysregulation in synapsin III knockout mice. Investigations are ongoing to extend these original observations and to relate them to other phenomenon known to occur in schizophrenia and other major psychiatric conditions. In addition, other animal models are being investigated.

2. Signal transduction in neurons.
(a) Synaptic vesicles as scaffolds for cellular signaling.
This project originated from the unexpected finding that synapsins, a family of synaptic vesicle associated proteins, regulates neurodevelopment. Our subsequent investigations revealed that synapsins regulate signal transduction, probably by affecting the composition of signalling complexes anchored to vesicles. The concept that vesicles serve as a platform for signal transduction is particularly important for retrograde neurotrophic signalling and other pathways initiated by receptor activation. Vesicle-mediated signal transduction potentially relevant for schizophrenia, major affective disorders, and Alzheimer's disease. Very little is known regarding the mechanism by which signalling is regulated on vesicles. These investigations, using synapsins as a tool, will enable us to better understand this important facet of signal transduction.
(b) Novel biosensors for cellular signaling.
The principal means by which cellular signaling is achieved is by protein phosphorylation pathways. Typically, activation of these pathways is monitored using either radioactive compounds or phosphorylation-state specific antibodies. Since the discovery of Green Fluorescent Protein (GFP), from Aequorea victoria many investigators have exploited this protein as a tool to detect physiological changes within the cell. A long-term goal of this project is to use these proteins to develop fluorescent biosensors for the detection of protein phosphorylation within living cells. Towards this goal, we have cloned a diverse collection of fluorescent proteins from marine life derived from the Great Barrier Reef of Australia, the Belizean Great Barrier Reef, and other locales. We are in the process of engineering these proteins to create new probes for the detection of protein phosphorylation.

funded research

The laboratory is funded by grants from the NIH.

Funding is available for postdoctoral research in this laboratory.