Zhongming Zhao, PhD, Vanderbilt University

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1 Οκτ 2013 (πριν από 4 χρόνια και 1 μήνα)

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Presentation


Session
:



Pathway
-
Assisted Investigation of Atypical Antipsychotic Drugs and
Serotonin Receptors in Schizophrenia




Zhongming Zhao
, PhD

Departments of Biomedical Informatics and Psychiatry

Vanderbilt University School of Medicine


Time/Date

Session






Abstract
:

Clozapine and its four related drugs (
olanzapine, quetiapine, risperidone and ziprasidone)
are the most frequently used treatments for schizophrenia in the world
. The underlying
mechanisms are not well understood. In this
study, we investigated the features of these
five drugs through their related genes at the pathway level. For each drug, we first
identified the pathways that the drugs might be involved in. We found that these five drugs
are all significantly involved in
five pathways, i.e., G
-
protein coupled receptor signaling,
cAMP
-
mediated signaling, serotonin receptor (5
-
HT) signaling, AMPK signaling, and cardiac
hypertrophy signaling. Among these pathways, the serotonin receptor (5
-
HTR) pathway is
an important neurotr
ansmitter
-
related pathway in psychiatric disorders. Therefore, we
further investigated the functional relationship between the five drugs and serotonin
receptors based on the experimental data of activation, chemical
-
protein interaction,
expression, inhabi
tation, and regulation of binding. We constructed a drug
-
5HTR network
including these five drugs, serotonin receptors, and their relationships and found that
clozapine has more interactors and more complicated connections with serotonin receptors
than the
other four drugs. Additionally, clozapine has two unique relationships with
HTR2A
,
one of the most susceptible candidate genes for schizophrenia. These results indicated that
clozapine might have a different action during the treatment process of schizophr
enia from
the other four drugs


Biographical Sketch:


Zhongming Zhao, PhD, is an Associate Professor in the Departments of Biomedical
Informatics, Cancer Biology, and Psychiatry, Vanderbilt University Medical Center. He is the
Chief Bioinformatics Officer
in Vanderbilt
-
Ingram Cancer Center (VICC), Head,
Bioinformatics Group,
Functional Genomics

Shared Resource (
FG
SR), and director,
Bioinformatics Resource Center (BRC). Dr. Zhao received his Ph.D. degree in human and
molecular genetics from the University of

Texas Health Science Center at Houston in 2000.
He also received three M.S. degrees: genetics from Peking University in 1996,
biomathematics from UT
-
Houston in 1998, and computer science from the University of
Houston in 2002. He has more than 13 years bi
oinformatics experience and published more
than 65 papers in the bioinformatics fields. He frequently serves as editorial board member
of scientific journals, program committee and scientific session chairs in the international
conferences, and reviewer of

grants and manuscripts.