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Student: Cathey L. Serrano
Mentor: Todd Prim
Title: "Gene Expression of Mycobacterium avium under variable temperatures"
Description: Working with RNA using RT/PCR and Differential Display to identify gene that are upregulated during certain conditions, specifically temperature differences. And also working with Mycobacterium Avium to see which genes are turned on (upregulated) at body temperature, that are not turned on at room temperature.

Student: De La Cruz, Miguel
Mentor: Joanne T. Ellzey
Title: "Morphometric analyses of histological and ultrastructural changes in liver cells associated with arsenic in drinking water"
Description: Morphometric analyses of the mitochondria, peroxisomes and smooth endoplasmic reticulum of C3H mice given sodium arsenate in drinking water are underway to determine if these organelles may swell or shrink in the presence of 5 ppm and/or 150 ppm arsenic in liver cells. Both quantitative and qualitative images at the light and electron microscope level are utilized. Cells as well as organelles are analyzed with images from a Zeiss Axioskop and a Zeiss EM-10 transmission electron microscope. Image Pro Express software is used for image analysis. Lipocytes as well as hepatocytes and nuclear cytoplasmic ratios as well as volume density data are being collected.

Student: Najera, Julia
Mentor: Lisa J. Bain
Title: "Activity and Specificity of the ATP-Binding Cassette Transporters "
Description: Examining ATP-dependent transport proteins that are involved in the elimination of compounds from the liver, kidney, and intestine. These transporters act to lower the concentration of the chemical and thus reduces its toxicity to the organism. Our research involves determining the physiological substrates transported by ATP-binding cassette proteins, elucidating toxicants which may interfere with these protein pumps, and determining how the transporters are regulated.

Student: Trisha foster
Mentor: Stephen Aley
Title: " DNA Sampling as a Tool for Final Assembly of DNA Shotgun Sequences"
Description: Because of the importance of Giardia lamblia both as a parasitic microorganism and as the earliest identified branch from the eukaryotic line of ascent, we have been part of a project to sequence the entire genome of this protist. The 12 million bp G. lamblia genome as been subjected to shotgun sequencing. Currently 95% of the genome has been sequenced with fewer than 1000 predicted gaps. To complete this assembly, existing "contigs" need to be located on a scaffolding of large genome insert clones known as Bacterial Artificial Chromosomes (BACs). To improve the efficiency and speed of this process we are experimenting with a sampling method for this process. In a sampling protocol small stretches of DNA randomly isolated from a given BAC are sequenced to identify all the contigs associated with that stretch of genomic DNA. This solution allows us to lower the nominal size of the "genome" being assembled from 12 million to mini-genomes of less than 200,000 bp. To investigate the feasibility of this process, we have taken inserts of DNA and digested them by NlaIII and Sau3A, resulting in a large numbers of small fragments. These fragments are size selected on an agarose gel and ligated together to minimize sequencing reactions. The string is then size fractionated again to obtain an optimum sequencing size. The sampled sequences are used to identify all contigs included in this mini-genome, simplifying assembly. We have demonstrated the feasibility of this process using medium size inserts, and we are currently working to adapt this process to full size BAC clones.

Student: Milka Montes
Mentor: Jorge gardea
Title: Study of the toxicological effects of heavy metals to convolvulus arvensis L (Morning glory) and its possible Phytoremediation Applications
Description: The purpose research is to determine the effects of heavy metals such as Cr(VI), Cd(II), Cu(II), Ni(II), Zn(II), and Pb(II) on the germination and growth of the plant Convolvulus arvensis L ( field bindweed), and the possible uptake and accumulation of the metals in the plant tissues. A variety of analytical techniques will be used including atomic absorption spectroscopy to determine the concentrations Advances: C. arvensis seeds were tested in agar-based media spiked with 0-40 ppm of Cd(II) Cu(II) and Cr(VI). The preliminary results indicate that C. arvensis plants exposed to 20 mg/L of these heavy metals, demonstrated capability to accumulate in the above ground plant parts more than 3,800 mg of Cr, 1,500 mg of Cd, and 560 mg of Cu per kg of dry tissues. Although all the concentrations utilized significantly reduced the plant parts elongation, none of them affected the dry mass accumulation in the leaves. The results found in this study, beside of the fact that this plant species has been found growing in harsh conditions, and the field data previously reported in the literature, corroborate that C. arvensis is a suitable candidate for the phytoremediation of Cd(II), Cr(VI), and Cu(II) contaminated soils. Furthermore, the concentration of Cr in dry leaves (2,100 mg/kg) could allow classifying C. arvensis as a potential Cr-hyperaccumulator plant species. Future work: (a)To test the effect of biochelators on heavy metal uptake. (b) To perform microscopy studies in order to evaluate metal movement inside the tissues.

Student: Hernandez, Cynthia
Mentor: Janying Zhang
Title: Aspects of Cancer
Description: Research in Dr. Zhang's lab currently focuses on three directions. First : The identification and characterization of tumor-associated antigens (TAAs) is currently underway. Autoantibodies against intracellular antigens have been described in many types of human cancer. How the intracellular molecules participate in the malignant transformation process and whether a similar mechanism in autoimmune diseases may be involved in humoral immune responses in cancer remain to be investigated. The rationale is that intracellular proteins, which are involved in carcinogenesis, are provoking autoantibody responses and therefore autoantibodies can be used to immunoscreen cDNA expression libraries to isolate, identify and characterize proteins, which might potentially be involved in malignant transformation. Using this approach, two novel cancer-related antigens (p62 and p90) have been identified in previous studies. This project will continue to focus on the identification and characterization of TAAs by using autoantibodies in sera from cancer patients for immunoscreening a cDNA expression library. As an alternative method, a proteome-based approach will be implemented in this project for the identification of TAAs the induce antibody responses in cancer. Second : The tumor-associated antigen array detection will be used for cancer diagnosis. The highly specific autoantibody response in systemic autoimmune disease generally predicts the biologic phenotype of the disease, making autoantibodies clinically valuable and diagnostically useful. Autoantibodies to cellular antigens have been extensively investigated in patients with different forms of cancer. Whether or not autoantibodies can be also used as markers for the diagnosis of cancer remains to be evaluated. Cancer has long been recognized as a multi-step process which involves not only genetic changes conferring growth advantages but also factors which disrupt the regulation of growth and differentiation. It is possible that some of these factors could be identified and their functions evaluated with the aid of autoantibodies arising during tumorigenesis. First, it will be determined whether it is possible to distinguish between antigens which are related to carcinogenesis and those which are related to other cellular processes such as proliferation or regeneration. Second, tumor-associated antibody-antigen systems will be identified, which are potentially useful for the early detection of cancer, and then the sensitivity and specificity of different antigen-antibody systems as markers in cancer will be evaluated for further developing "tumor-associated antigen array" system for cancer diagnosis, prediction, and for following the response of patients to treatment. Third : epidemiological study of liver cancer from the population of the Paso del Norte Region in the US-Mexico Border. Based on data from the Texas Cancer Data Center (www.txcancer.org), the death rate of liver cancer for all races in Texas in 1998 was 7.36 (per 100,000) in males and 3.16 in females. However, the death rate of liver cancer in Hispanics was 13.67 in males and 5.80 in females, which is the highest of all the ethnic groups reported. (For example, the death rates of liver cancer in white males and females were 5.35 and 2.53, respectively). Which factors are the important risk factors in the development of liver cancer in the Hispanic population remain unknown. The proposed research will involve a case-control study to investigate risk factors in the development of liver cancer and by using these epidemiological studies relate genetic, environmental, dietary and lifestyle factors to the etiology of liver cancer in the Hispanic population.

Student: Martinez, Liliana
Mentor: Sukla Roychowdhury
Title: "Microtubule-G protein Interactions in Normal and Cancer Cells"
Description: The goal of the proposed research is to test the possible relationship between G-protein-mediated signaling and microtubule assembly/organization in cells. The hypothesis that this process is important for cell growth and cell division will also be tested. It is further hypothesized that altered interaction between microtubules and G proteins (specific defects in G protein a subunit genes have been identified in sporadic endocrine tumors) contribute to the development of cancer. Heterotrimeric G proteins play a central role in transmembrane signaling pathways by coupling a wide range of receptors to their effectors molecules. Considerable evidence also suggests that G protein mediated signaling might regulate microtubule dynamics in cells. Recently, we have observed that a and bg? subunits of G proteins regulate microtubule assembly in vitro [Roychowdhury et. al (1999) J. Biol. Chem. 274, 13485-13490; Roychowdhury and Rasenick (1997) J. Biol. Chem. 272, 31476-31581]. G protein subunits are shown to associate with microtubules in NIH3T3 and PC12 cells (Martinez and Roychowdhury, unpublished observation). Since, the polymerization and dynamics of microtubules are central to their functions, it is unquestionable that any defect in the regulation of microtubule dynamics in cells would lead to major disorders. Thus, abnormal interaction between microtubules and G proteins may lead to defects in cell growth and differentiation, which in turn may contribute to the development of cancer. To accomplish these goals, experiments will be conducted using NIH3T3 (fibroblast cells), colon and uterus cancer cell lines. It will be determined if the activation of G proteins modulate microtubule dynamics (polymer-monomer equilibrium) in NIH 3T3 cells by mobilizing G protein subunits to bind to tubulin /microtubules and if the effect is altered in cancer cell lines. NIH3T3 cells will be treated with various growth factors (thrombin or EGF) or will be arrested in mitotic phase of cell cycle by cell synchronization. Alteration of tubulin-G protein association and polymer-monomer equilibrium will be determined. These studies will reveal a novel role of G-proteins in regulating microtubule assembly in cells, as well as the role of tubulin-G protein interactions in cell division and development of cancer.

Student: Ireland Jamie, Salicru Mauricio
Mentor: K.M. Garza
Title: "Autoimmune disease as mediated through T cells"
Description: One of the key players in an immune response is the T lymphocyte. T cells recognize and respond to very specific components, or antigens, of a foreign agent and proceed to perform a series of different effector functions that partake in the elimination of the agent. In autoimmunity, T cells that are specific for self antigens perform effector functions that cause tissue damage. It remains unknown as to how these self-reactive T cells become activated. One objective of our work is to examine the underlying mechanisms that lead to the initiation and progression of autoimmune disease as mediated through T cells. In particular, our lab is interested in elucidating the cellular and molecular mechanisms by which CD4+ and CD8+ T cells are tolerized and activated with emphasis on the role this plays in the induction and progression of T cell-mediated autoimmune diabetes mellitus. We utilize an experimental mouse model for our studies, taking advantage of both transgenic and knockout gene technology to assess the role of certain cell lineages or molecules in autoimmunity.

Student: Name
Mentor: Tony Flores
Title: Louis Irwin
Description: "Effect of Environmental and Behavioral Stimulation on Gene Expression in the Rat Brain."