Associate Professor of Biology, Director of Bioinformatics
Office: 429 Smith Hall
||Biology, University of Houston
||Biochemistry, University of Houston
||Post-Doctoral Associate, Dept. of Developmental Neurobiology, St. Jude Children's
Research Hospital, Memphis
||Assistant Professor, Dept. of Neurology, University of Tennessee Health Science Center
||Adjunct Assistant Professor, Dept. of Anatomy and Neurobiology, University of Tennessee
Health Science Center
||Associate Professor, Dept. of Biology, University of Memphis
||Adjunct Associate Professor, Dept. of Neurology, University of Tennessee Health Science
- Heinrich K, Silver B, Berry M, Homayouni R. GeneIndexerTM, Computable Genomix, LLC,
Memphis TN. http://computablegenomix.com/
- Xu L, Furlotte N, Lin Y, Berry MW, George EO, Homayouni R. GeneSet Cohesion Analysis
Tool, University of Memphis, 2011, http://binf1.memphis.edu/gcat/
- Vadlamudi L, Jones LA, Homayouni R., ColonyTrak, University of Memphis, 2011, http://binf1.memphis.edu/ColonyTrak/
- Chen Z, Homayouni R: DegenDesigner©, University of Houston, TX 1993. DegenDesigner©
is a computer program for designing optimum degenerate oligonucleotides from limited
peptide sequence information.
- Hardin S, Homayouni R, Hardin P: "Optimized primer library for gene sequencing and
method of using same," University of Houston, TX, 1996. U.S. Patent #6,083,695 issued
on July, 2000
- Homayouni R, Heinrich K, Wei L and Berry M: Semantic Gene Organizer© (2002-2004) University
of Tennessee Health Science Center, Memphis, TN. http://shad.cs.utk.edu/sgo/sgo.html
My research interests are in three broad areas: 1) Mechanisms underlying neurodegeneration
and Alzheimers Disease; 2) Mechanisms of mammalian brain development; 3) Application
& Text-mining methods to Genomics and Bioinformatics; 4) Genomics and Bioinformatics.
Current research projects in my lab are summarized below.
Role of Amyloid Precursor Protein during normal development and in neurodegeneration
associated with Alzhiemers Disease
Amyloid precursor protein (APP) is a transmembrane glycoprotein that plays a critical
role in the pathogenesis of Alzheimers Disease. Presently, the physiological role
of APP and its family members, amyloid precursor like protein 1 and 2 (APLP1 and APLP2),
are unclear. Recent genetic studies in mice indicate that APP family proteins have
essential and partially overlapping roles during development. APP family proteins
have several structural features that are highly conserved. In addition, all three
proteins are similarly processed by specific proteases in intracellular compartments.
The proteolytic processing of APP is remarkably similar to that of Notch1, a transmembrane
protein that is important in early development. Binding of extracellular ligands to
Notch1 stimulates proteolysis and release of its intracellular domain which translocates
into the nucleus and regulates gene expression. Recent studies indicate that the cytoplasmic
domain of APP is released, enters the nucleus, and together with Fe65 adapter protein
activates transcription, suggesting that APP is involved in a Notch-like signaling
pathway during development. My laboratory is testing the hypothesis that APP family
proteins function in a notch-like signaling pathway during brain development. We use
a variety of molecular, cellular and genomic approaches to identify components in
APP signal transduction pathway using genetically modified mice that lack a combination
of APP family genes. One approach in the lab focuses on identification of ligands
that bind to the extracellular domain of APP family proteins and modulate their internalization
and processing. Another approach focuses on investigation of the role of APP family
proteins in regulation of gene expression using DNA microarrays. Understanding the
physiological function of APP family proteins may shed light into the molecular mechanisms
underlying pathogenesis of Alzheimers disease.
Role of Dab2IP, a novel GTPase activating protein, in the Reelin signaling pathway
during brain development
The mammalian brain is formed through a series of intricately orchestrated events
whereby neurons born in germinal zones migrate great distances to reach their final
positions and form specific connections. Abnormalities in neuronal migration and positioning
are believed to be responsible in part for disorders such as lissencephaly, pediatric
epilepsy, schizophrenia and autism. Recent genetic studies in mice have identified
a key signaling pathway that controls cell positioning and formation of laminated
structures throughout the mammalian brain. Mice with disruptions in reelin, disabled-1
(Dab1), or both very low-density lipoprotein receptor (VLDLR) and apolipoprotein E
receptor 2 (ApoER2) genes exhibit nearly identical histopathological abnormalities.
Reelin is an extracellular protein that directly binds to the lipoprotein receptors
and induces tyrosine phosphorylation of Dab1. Dab1 is an intracellular adapter protein
that is required for Reelin signaling. The long-range goal of this project is to
identify molecular components downstream of Dab1 in the Reelin signaling pathway and
to understand the mechanism by which Reelin controls neuronal positioning. Using a
yeast two-hybrid strategy, we found that Dab1 interacts with amyloid precursor family
proteins, protocadherin-18 and a novel protein similar to GTPase activating proteins,
termed Dab2IP. The deduced amino acid sequence of Dab2IP encodes a Ras GAP related
domain and several protein-protein interaction domains, including an NPxY PTB-interacting
motif. We hypothesize that Dab2IP functions as a regulator of GTPases and, by virtue
of its interaction with Dab1 and other intracellular proteins, is the downstream effector
in the Reelin signaling pathway. Future aims in this project include: 1) Characterization
of the activity, regulation and cellular function of Dab2IP; 2) investigation of the
effect of Dab1 on Dab2IP activity; 3) investigation of the physiological role of Dab2IP
by targeted disruption in mouse. Understanding the biological function of Dab2IP and
its role in Reelin signaling will provide valuable insight into the molecular mechanisms
of neuronal migration and cell positioning during brain development.
Gene clustering using Latent Semantic Indexing of MEDLINE abstracts
Recent advances in genomics and DNA microarray technology enable investigators to
simultaneously analyze the expression of thousands of genes under different experimental
conditions. However understanding the functional relationships between co-regulated
genes presents a formidable task to investigators, requiring first hand knowledge
of the biological characteristics of ea`ch gene. There are a variety of public electronic
resources from which investigators may assemble gene information. For instance, there
are over 10,000 annotated human genes in LocusLink and nearly 13 million citations
archived in MEDLINE. However, better automated tools are needed to aid in extraction
and utilization of gene information from these databases. My lab has been collaborating
with Dr. Michael Berry (Professor of Computer Science at The University of Tennessee,
Knoxville; http://www.cs.utk.edu/~berry/) to develop a new software environment called Semantic Gene Organizer©(SGO) ( http://shad.cs.utk.edu/sgo/sgo.html ) to automatically extract gene relationships from titles and abstracts in MEDLINE
citations. SGO utilizes a variant of the vector-space model of information retrieval
called Latent Semantic Indexing (LSI). LSI implements a classical factorization method
from linear algebra (singular value decomposition) to identify conceptual relationships
between documents. Our studies have provided proof-of-principle that LSI is a robust
automated method for identification of gene-to-keyword and gene-to-gene relationships
from the biological literature. Future aims of this project include: 1) expansion
of the gene-document collection to include all genes in the LocusLink database; 2)
Utilize SGO to expand gene ontology terms and functional gene annotation.
Past and Present Laboratory Personnel
|Xiaofan Li, MD
||Post-Doc, University of Texas, Houston
|Lai Wei, MD
||St Jude Children's Hospital
||CEO, Computable Genomix, LLC
||Student, Univesity of Tennessee Allied Health
||Student, Univeristy of Memphis Nursing
|Sun-Hong Kim, MS
||Johns Hopkins University
|Lijing Xu, MS
|Hemachand Tummala, PhD
|Lynn Jones, PhD
|Alla A. Peselis
||University of Rhode Island
||University of Memphis Public Health
||University of Arkansas
- Roy S, Homayouni R, Berry MW, Puretskiy A. Nonnegative tensor factorization of biomedical literature
for analysis of genomic data. Proceedings of the 11th SIAM International Conference on Data Mining, 2011.
- Roy S, Heinrich K, Phan V, Berry MW, Homayouni H. Latent Semantic Indexing of PubMed abstracts for identification of transcription
factor candidates from microarray derived gene sets. BMC Bioinformatics, Suppl 10:S19, 2011.
- Furlotte NA, Xu L, Williams RW, Homayouni R. Literature-based evaluation of microarray normalization procedures. Proceedings of IEEE conference on Bioinformatics and Biomedicine, 608-12, 2011.
- Rouchka EC, Flight RM, Homayouni R. Proceedings of the Tenth Annual UT-ORNL-KBRIN Bioinformatics Summit 2011. BMC Bioinformatics, Suppl 7:A1, 2011.
- Cashion A, Stanfill A, Thomas F, Xu L, Sutter T, Eason J, Ensell M, Homayouni R. Expression
levels of obesity-related genes are associated with weight change in kidney transplant
recipients. PLoS One. 2013;8(3):e59962. doi: 10.1371/journal.pone.0059962. Epub 2013
Mar 27. PubMed PMID: 23544116; PubMed Central PMCID: PMC3609773.
- Qiao S, Kim SH, Heck D, Goldowitz D, LeDoux MS, Homayouni R. Dab2IP GTPase activating
protein regulates dendrite development and synapse number in cerebellum. PLoS One.
2013;8(1):e53635. doi: 10.1371/journal.pone.0053635. Epub 2013 Jan 9. PubMed PMID:
23326475; PubMed Central PMCID: PMC3541190.
- Xu L, Cheng C, George EO, Homayouni R. Literature aided determination of data quality
and statistical significance threshold for gene expression studies. BMC Genomics.
2012;13 Suppl 8:S23. doi: 10.1186/1471-2164-13-S8-S23. Epub 2012 Dec 17. PubMed PMID:
23282414; PubMed Central PMCID: PMC3535704.
- Lee GH, Kim SH, Homayouni R, D'Arcangelo G. Dab2ip regulates neuronal migration and
neurite outgrowth in the developing neocortex. PLoS One. 2012;7(10):e46592. doi: 10.1371/journal.pone.0046592.
Epub 2012 Oct 4. PubMed PMID: 23056358; PubMed Central PMCID: PMC3464295.
- Swanson JM, Wood GC, Xu L, Tang LE, Meibohm B, Homayouni R, Croce MA, Fabian TC. Developing
a gene expression model for predicting ventilator-associated pneumonia in trauma patients:
a pilot study. PLoS One. 2012;7(8):e42065. doi: 10.1371/journal.pone.0042065. Epub
2012 Aug 15. PubMed PMID: 22916119; PubMed Central PMCID: PMC3419717.
- Roy S, Heinrich K, Phan V, Berry MW, Homayouni R. Latent Semantic Indexing of PubMed
abstracts for identification of transcription factor candidates from microarray derived
gene sets. BMC Bioinformatics. 2011 Oct 18;12 Suppl 10:S19. doi: 10.1186/1471-2105-12-S10-S19.
PubMed PMID: 22165960; PubMed Central PMCID: PMC3236841.
View more references (pubmed link)