LABORATORY ROTATIONS FOR PATHOLOGY PhD STUDENTS:
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| Faculty | Projects | Techniques |
| Berse | Regulation of gene expression in neurons:
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| Blusztajn |
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| Murnane | Characterization of human primary tumors for proteinase profiles. Defining cancer subtypes and different pathways of cancer progression. Enzyme markers in human tumors. Regulation of proteolytic enzymes by ras . |
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| Sharon | Engineering, characterization and efficacy testing of polyclonal antibody libraries against cancer and infectious diseases |
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| Slack | Elucidation of signal transduction pathways regulating secretory processing of the amyloid precursor protein (APP) of Alzheimer’s disease in cultured mammalian cell lines: role of calcium influx, protein kinase C subtypes and tyrosine kinases/phosphatases .
Comparison of APP processing pathways in fibroblast cultures obtained from normal donors and donors with Alzheimer’s disease. |
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| Faculty in Other Departments | ||
| Botchkarev | Molecular mechanisms controlling hair follicle growth in health and disease. Our research is focused on four major projects:
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Generation of transgenic mice, pharmacological manipulation of hair follicle growth in vivo, ex vivo culture of isolated hair follicles and skin explants, isolation of the lymphocyte subsets from skin and peripheral blood, in situ hybridization, double and triple immunofluorescence , multi-color confocal microscopy, Western blot analysis, RT-PCR, FACS analysis |
| Cardoso | Control of branching morphogenesis and epithelial cell differentiation during lung development. The overall goal is to Identify and characterize potential regulators Of lung morphogenesis, and to study how they interact with the gene network present in the early lung bud. Some regulators we are studying include:
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| Eller | Our work focuses on the mechanisms of DNA damage responses to telomere uncapping in mammalian cells and how these responses can be stimulated by DNA oligonucleotides homologous to the telomere 3′ overhang. We are particularly interested in the apoptotic response in cancer cells and how this technology may be therapeutic in the treatment of human cancer. |
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| Faller | A major focus of our laboratory is the study of the basic molecular and cellular biology of virus- and oncogene -transformed cells and tumors. We are involved in determining the mechanisms by which retroviruses and their oncogenes cause tumors, through defining the ways in which oncogenes control host cell gene expression. A special interest of this laboratory involves viral regulation those cellular genes encoding proto- oncogenic molecules and cytokines. We are analyzing the molecular mechanisms by which oncogene -transformed cells become autonomous of growth factor requirements. This work involves the elucidation of growth-factor signal transduction pathways in normal and trans-formed mesenchymal and lymphoid cells, and study of the ways in which this signaling pathway is disrupted or circumvented in tumor cells. This work has resulted in new information regarding the transduction of growth factor signals by second messenger systems in both normal and transformed cells. My laboratory also studies the role of oncogenes in programmed cell death. A related area of his research is the interaction of retroviruses and the tumors they induce with cellular immune defense mechanisms. The means by which virus- or tumor-specific cytotoxic T lymphocytes, natural killer cells and monocytes recognize and destroy infected cells and tumors is under investigation, as are the molecular mechanisms by which tumors escape from immune surveillance. The mechanisms of aberrant control of Class I Major Histocompatibility Antigen gene expression in oncogene -transformed cells, retrovirus-infected cells and naturally-occurring tumors are being deter-mined. A new transactivation property of murine leukemia viruses has been elucidated, which controls the expression of genes in the host cell important to the leukemogenic process. My laboratory also has a translational research program which develops molecular cancer therapeutics derived from his basic research, and tests them in clinical trials. | |
| Freddo | Diseases of the ocular anterior segment and ocular tumors. |
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| Goukassian |
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Tissue culture, FACS analysis (proliferation, apoptosis, gene expression). Conventional and confocal microscopy, immunohistochemistry , ribonuclease protection assay, Electromobility Shift Assay (E2F1, p53, NFkB transcription factors), transient transfections , gene expression in murine and mammalian cells ( AdTetOn /Off system), Western, Northern blots, immunoprecipitation , PCR, RT-PCR, routine histology, protein phosphorylation studies, reporter plasmid analyses, several gene knockout and double transgenic murine models (XPA, XPC, p53 and combinations of these gene knockouts with LacZ (mutation frequency sensor gene) evaluation of transdermal penetration. |
| Lerner | There are two principle areas of research:
Research area #1: My research on human lymphoid malignancies focusses on cAMP and cGMP signalling in B and T cells and the use of family specific phosphodiesterase inhibitors to selectively induce apoptosis in malignant cell populations. We have determined that PDE4 inhibitors induce apoptosis in chronic lymphocytic leukemia cells but not in human mononuclear cells. In addition, we have determined that a new effector protein for cAMP , EPAC, a Rap1 GDP exchange factor that binds to and is activated by cAMP , is expressed and functional in CLL cells but in no other hematopoietic cell examined ( ie B cells, T cells, monocytes , neutrophils ). Possible projects would be:
Research area #2: We wish to determine what physiologic and pathologic roles a novel Ras superfamily GDP exchange factor, AND-34, plays in breast cancer cells and in lymphoid cells. AND-34 (or its human homologue, BCAR3) induces tamoxifen resistance in breast cancer cell lines when over-expressed. It is phosphorylated after EGF treatment. A possible project would be to identify the tyrosine that is phosphorylated following EGF treatment and establish what effect mutation of this tyrosine residue has on AND-34’s GEF activity. |
Tissue culture, FACS analysis, stable and transient transfections , retroviral infections, Mitenyi magnetic bead purification of primary human hematopoietic cells, quantitative PCR, Northeres , Southerns , Western analysis by ECL, immunoprecipitation , recombinant DNA techniques, immunohistochemistry , enzymatic analyses, kinase assays, luciferase assays, “knockout” mouse generation and analysis. |
| Park | 1. Role of PKC and PKA in human pigmentation. This project investigates how these two signaling pathway crosstalk and interact to regulate melanogenesis , the process resulting in skin color.
2. Role of wound fluid collected from chronic wounds on healing. This project investigates what factors in the wound fluid are responsible for suppressing proliferation of keratinocytes and fibroblasts, two cell types critical for proper wound healing. |
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| Rosenberg | Even the earlierst breast cancers contain recurrent genetic abnormalities, implying that precursor lesions exist, containing abnormalities important to the earliest steps of oncogenesis . Research in this lab is directed at identifying and understanding genetic events occurring before the appearance of the full-blown malignant phenotype. We are investigating:
In addition, we are using LOH combined with statistical methods to study genetic differences between breast tumors:
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| Sherr | Development of the immune system. Immunoregulation /autoimmunity. Intracellular signals leading to deletion of lymphocyte subsets through apoptosis, with emphasis on preB cells in bone marrow cultures. The role of pollutant- specific DNA-binding receptors in Induction of apoptosis and transformation. | Cellular immunology, long-term Marrow cultures, flow cytometry Analysis and sorting, western blotting, Molecular biology (cloning, transfections , gene knock-out mice, northern and Southern blotting, PCR). |
| Sullivan | Our experiments are focused on the conserved CENP-A, the H3-like centromeric histone , which is the foundation of the kinetochore . CENP-A contributes to a unique type of chromatin that gives rise to a conserved kinetochore configuration that is critical for centromere function and regulation. We are interested in how CENP-A contributes to centromere assembly and chromosome stability in normal and neoplastic cells and how DNA sequence may specify centromere identity. My lab uses immunocytological , molecular, genetic and biochemical techniques, as well as high-resolution microscopy ( deconvolution ) to address questions about eukaryotic centromere structure and function. Some of our projects include:
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Techniques: ChIP , IP, immunofluorescence , FISH, pulsed field gel electrophoresis, cell culture, transfection , cytogenetics , PCR, RNAi , western blotting, fly genetics and screens, 3D cell preparation and deconvolution microscopy, southern blotting. |
| Thiagalingam | The overall research interest of our laboratory is in the use of cancer genomics, employing primarily breast and lung cancers as model systems, to invent new tools for diagnosis, management and therapy of cancer.
Disabled Smad signaling in cancer has become increasingly recognized as an important step that affects processes such as loss of growth inhibition, promotion of ngiogenesis and metastasis and the epithelial mesenchymal transition. Although frequent alterations in Smad4 have been primarily reported in pancreatic and gastrointestinal cancers, the nature of defects involving the Smad signaling pathways has been elusive in other cancers potentially due to alternate mechanisms and/or targets of the signaling pathway, which become inactivated. Recently, we developed a novel technique known as TEGD to analyze the Smad genes in cancer. We demonstrated for the first time that the loss of Smad8 expression is associated with multiple types of cancers including 31% of both breast and colon cancers due to epigenetic silencing via DNA hypermethylation of intron1 of the gene. Currently, our major interest in the Smad project is to delineate the role(s) of the various Smad signaling pathways in metastatic cancer. Our other research interests include furthering the understanding of alternate targets/modes of inactivation of p53 and elucidating the molecular basis of the genesis of sporadic lung cancer caused by tobacco smoke derived carcinogens. We hypothesize that the loss of p53 mediated signaling in tumors without mutations might result from a defect in an upstream event and have successfully isolated known and novel genes that modulate p53 function using a yeast double selection system. The characterization of these genes is in progress. We have also formulated several experimental strategies to define the genetic and epigenetic determinants for individual susceptibility to DNA damage in smokers. |
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| Thomas |
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| Vaziri |
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| Yaar |
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Cell culture, Western and Northern blot analysis, Plasmid propagation, RT-PCR, animal experiments, tranfection and promoter analysis |