Glasgow, Ben, M.D.

Research Area: Molecular Mechanisms of Tear Film Formation

Research Interests: The laboratory is focused in 3 areas, the structure and function of tear proteins, the genetic events that contribute to ocular melanomas and the study retinal microvasculopathy of AIDS.
     Tears contain a variety of proteins that protect the ocular surface. The overall goal is to learn the role of proteins in the molecular mechanisms of tear film function. Current efforts are focused on learning the structure, ligand specificity and the molecular basis of selectivity, for a group of lipid binding proteins in tears.
     A second project concerns the unraveling of the genetic events that contribute to the pathogenesis of ocular melanomas.
Unique differences between ocular melanoma tissue and its normal counterpart are sought.
     A third project addresses pathogenesis of retinal microvasculopathy and its relationship to retinitis caused by cytomegalovirus. This virus causes a severe necrotizing retinitis and is the major cause of blindness in AIDS.

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Liu, Xin, M.D., Ph.D.

Research Area: Molecular Genetics of Mammalian Neurodevelopment, Neurological disease, and Biological Clock.

Research Interests: Our research is aimed at understanding the molecular basis of neurodevelopment, neurodegenerative diseases, and behavior. We use gene targeting in mice to define the in vivo functions of three groups of molecules.

The first group of molecules are neurotrophins (NTs). NTs play important roles in regulating neuronal survival and neuroplasticity, both of which are critical for the formation of a functional nervous system. NTs may also promote neuronal survival in stroke or neurodegenerative diseases such as ALS, Huntington’s disease, and Alzheimer’s disease. We have derived mouse strains that lack different types of NTs and concluded that NTs are essential for the survival of peripheral sensory neurons during development. We are currently focusing on NTs’ role in central nervous system development and in stroke.

The second group of molecules are Presenilin1(PS1) and d-catenin. Mutations in PS1 can lead to early onset of Alzheimer’s disease. d-catenin interacts with PS1 and is expressed exclusively in the brain. d-catenin may also be part of synaptic adhesion.

These features indicate that d-catenin may play an important role in Alzheimer’s disease. We are deriving mice that either overexpress delta-catenin or lack the expression of d-catenin. We believe that analysis of these mutant mice will provide insights into Alzheimer’s disease.

The third group of molecules are mPer1, mPer2, mPer3, and Clock. These molecules control the circadian clock in mouse. We are using these molecules to study the cellular organization and the intracellular signaling which make the biological clock.

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Vinters, Harry, M.D.

Research Area: Molecular neuropathogenesis of human CNS/PNS disease

Research Interest: We approach several diseases of the human nervous system using various immunohistochemical and molecular approaches aimed at understanding their etiology and pathogenesis. Areas of current interest include parenchymal (especially Alzheimer type) and vascular dementias, focusing on the etiopathogenesis of cerebral microvascular disease related to amyloid deposition in microvessel walls; cell biology of expression within the CNS of genes related to cerebral cortical malformations--particular emphasis currently on two genes associated with the autosomal dominant condition, tuberous sclerosis. We are interested in gene product localization within human brain, and also in vitro approaches to study gene effects.

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Gatti, Richard, M.D.

Research Area: Molecular Pathology of Ataxia-Telangiectasia and Related Disorders

Research Interests: Since 1985, we have been attempting to localize the gene(s) for ataxia-telangiectasia (AT) to a region small enough to clone and isolate so that we can develop a better understanding of this progressive and fatal disease of children. In July 1988, we localized the gene to chromosome 11q22-23 by linkage analyses. We formed an international consortium and analyzed over 200 families. In 1995, the ATM (A-T mutated) gene was cloned by the Israeli members of the consortium and found to have protein kinase homology.

Our lab is presently focusing on:

1. Characterizing ATM mutations, most of which result in protein truncation, and developing "user-friendly" detection assays.

2. Using ATM cDNA and monoclonal antibodies to localize the ATM gene product in tissues from 11 autopsies of A-T patients as well as in cell extracts from >150 patients.

3. Cloning the >200 million-year-old Pufferfish ATM homology.

4. Cloning ATM cDNA into vacinnia vectors to allow study of ATM protein structure.

Our long-term goals are gene-based therapy for A-T patients, and diagnostic testing for patients and carriers.

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