Education

1989	B.S.	Biology, University of Houston
1996	Ph.D.	Biochemistry, University of Houston

Professional Experience

1996-2001	Post-Doctoral Associate, Dept. of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis
2001-2006	Assistant Professor, Dept. of Neurology, University of Tennessee Health Science Center
2001-present	Adjunct  Assistant Professor, Dept. of Anatomy and Neurobiology, University of Tennessee Health Science Center
2001-present	Associate Professor, Dept. of  Biology, University of Memphis
2001-present	Adjunct Associate Professor, Dept. of Neurology, University of Tennessee Health Science Center

Intellectual Property

• 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

Research Interests

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

Name	Lab Role	Duration	Current Position
Xiaofan Li, MD	PhD student	2001-06	Post-Doc, University of Texas, Houston
Lai Wei, MD	PhD student	2002-06	Post-Doc, NIH
Yang Li	Tech	2002-03	St Jude Children's Hospital
Kevin Heinrich	PhD student	2004-07	CEO, Computable Genomix, LLC
Ngoc Nguyen	Undergrad tech	2006-07	Student, Univesity of Tennessee Allied Health
Rachael Mangerchine	Undergrad tech	2006-07	Student, Univeristy of Memphis Nursing
Jong Kim	Res Associate	2007
Sun-Hong Kim, MS	PhD student	2002-08	Johns Hopkins University
Lijing Xu, MS	Res Associate	2003-present
Hemachand Tummala, PhD	Res Associate	2006-2008
Lynn Jones, PhD	Res Associate	2006-present
Suhong Qiao	Res Associate	2007-present
Sarani Ghoshal	PhD Student	2007-present
Alla A. Peselis	Undergrad Tech	2008-2009	University of Rhode Island
Terra Tongumpun	Undergrad Tech	2008-2010	University of Memphis Public Health
Sasha Bass	Undergrad Tech	2009-2011
Farimah Salami	PhD student	2009-present
Tammy Hamilton	Undergrad Tech	2011-2012	University of Arkansas
Sheetal Bhatara	MS Student	2011-present
Maria Perez	Undergrad Tech	2012-present