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What is Creutzfeldt Jakob Disease? Is it Autoimmune? |
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Yes |
| Variant Creutzfeldt-Jakob Disease (vCJD), is a fatal disease of the nervous system in humans. In the United States,the average age of patients with vCJD is 26 years, as opposed to 68 years for those who contract Creutzfeldt-Jakob Disease (CJD). This age discrepancy led researchers to look carefully at the younger patients and to uncover the connection between vCJD and Mad Cow Disease. On the basis of observable symptoms, probable cases can be diagnosed. However, confirmation of vCJD cases requires examination of patients’ brain tissue after death. |
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Ansell, Stephen M., M.D., Ph.D. B-cell non-Hodgkin's lymphoma involves the neoplastic transformation of B-lymphocytes. In the areas of B-cell lymphoma, however, intratumoral T-lymphocytes are also seen and we have shown that the presence of increased numbers of intratumoral CD4+ T-cells predicts a better clinical outcome. Our lab is currently investigating the phenotype and activity of these intratumoral T-cells and developing strategies to modulate the T-cell infiltration in areas of B-cell lymphoma.
Further areas of research interest include the development of biologic therapies for non-Hodgkin's lymphoma. The current strategies being developed include the use of novel antibodies and cytokines, the use of antisense oligonucleotides, and the development of strategies to inhibit signaling through receptors that promote the survival of malignant B-cells.
The utility of these strategies is being tested in early phase clinical trials. These studies are being conducted within the Division of Hematology at the Mayo Clinic, the Mayo Clinic Cancer Center, and the North Central Cancer Treatment Group.
See a listing of my publications
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| Rebecca
S. Bahn, M.D. |
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email |
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Pathogenesis of Graves' Ophthalmopathy and Autoimmune Thyroid Disease
Our laboratory is interested in the mechanisms and consequences of immune system activation of orbital preadipocyte fibroblasts, the target cells involved in Graves' ophthalmopathy (GO). We are studying the unique features of these that render them particularly susceptible to autoimmune attack in Graves' disease. Studies are underway to define retro-ocular, thyroid and pretibial cross-reactive antigens whose presence might help to explain the clinical associations between GO, pretibial dermopathy, and Graves' hyperthyroidism. We have shown that thyroid stimulating hormone receptor (TSHR), the autoimmune target in Graves' hyperthyroidism, is expressed to a greater degree in orbital connective tissue explants from patients with Graves' ophthalmopathy than in normal orbital tissue. This antigen appears to be expressed in the fat cells within the orbit. Our in vitro studies have shown that TSHR expression in orbital preadipocytes is closely associated with adipogenesis. We have shown that factors impacting adipogenesis, including interleukin-6,interferon-gamma, and the PPAR-gamma agonist rosiglitazone,appear also to have effects on TSHR expression in these cells. Other studies in our laboratory include the analysis, using gene array technology, of genes involved in the development of GO. We have identified several adipogenesis-related and immune system genes that may have novel roles in this disease process. Finally, we are developing a mouse model of GO to use in studies of novel treatments for this condition.
| Rita
Basu, M.D. |
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My research interests include investigating the various mechanisms responsible for abnormal glucose metabolism in individuals with diabetes and pre-diabetes. I am interested to know what are the reasons for higher fasting and post meal glucose concentrations in people with impaired fasting glucose and type 2 diabetes. I am also looking at the mechanisms by which cortisol plays a role in carbohydrate metabolism. Recent studies that we conducted have shown that the splanchnic bed makes cortisol in humans via the enzyme 11betahydroxysteroid dehydrogenase type 1, now I am following up on this and looking at what modulates splanchnic and whole body cortisol production..is it mediated by the pituitary-hypothalamic axis or by degree of visceral adiposity, does nutrient ingestion and or incretins/insulin modulate this process?
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| Peter
L. Bergsagel, M.D. |
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Molecular Pathogenesis of Multiple Myeloma
Multiple myeloma (MM) is a tumor of mature, isotype switched plasma cells. It is a uniformly fatal malignancy that is frequently preceded by a common (1% of adults), benign pre-clinical phase, monoclonal gammopathy of undetermined significance (MGUS). Our laboratory is focused on understanding the molecular events that lead to the development of MGUS, and to its progression to MM. In the last few of years we have determined that MM is characterized by recurrent chromosome translocations to the immunoglobulin heavy chain gene on 14q32. We have cloned over 35 translocation breakpoints, and identified five frequent translocation partners, that are present in almost one half of patients with MM. The translocations appear to be initiating events in the tumorigenic process, and are present in MGUS. From a detailed analysis of the breakpoints it is clear that the translocations are frequently mediated by aberrant activity of B cell specific mechanisms: somatic hypermutation and isotype switch recombination.
We have cloned six translocation breakpoints on 11q13, from 50-300kb upstream of cyclin D1, associated with the ectopic expression and dysregulation of cyclin D1 mRNA and protein, and translocation breakpoints on 6p21 that dysregulate cyclin D3. We have cloned 7 translocation breakpoints on 4p16.3, from 50-120kb upstream of Fibroblast Growth Factor Receptor 3 (FGFR3). The t(4;14) is a novel, karyotypically silent translocation associated with the ectopic expression and dysregulation of FGFR3 on der14 mediated by the 3' enhancer of the IgH locus. In addition there is dysregulation of a novel SET domain protein that we have called MMSET, mediated by the intronic enhancer on der4. We have cloned five translocation breakpoints on 16q23, within approximately 500 kb of c-maf. The t(14;16) is also a novel, karyotypically silent translocation that is associated with the ectopic expression and dysregulation of c-maf mRNA. In addition we have cloned translocation breakpoints on 20q11 that result in dysregulation of mafB, highlighting the importance of maf family members in MM
We are now using murine and in vitro models to study ectopic gene expression mediated by somatic hypermutation and isotype switch recombination, and to develop faithful mouse models of myeloma. We have generated several different transgenic vectors, both conventional, and using BACs, to ectopically express genes in plasma cells. We are analyzing transgenic mice that express FGFR3, MMSET, c-maf, cyclin D1 in plasma cells. We are studying how the ectopic expression of cyclin D1, FGFR3 and c-maf contribute to plasma cell neoplasia, and how they may be used as therapeutic targets. The novel protein MMSET is expressed in developing T cells, and germinal center B cells. We have generated a conditional murine allele to study it role in normal lymphocyte development, and we are pursuing a biochemical characterization of its function and protein partners in lymphocyte development. We are continuing our analysis and cloning of novel translocation breakpoints and oncogenes and we are using microarray gene expression analysis to identify other molecular targets in myeloma.
See a listing of my publications
http://mayoresearch.mayo.edu/mayo/research/staff/bishop_at.cfm hand surgery?
http://mayoresearch.mayo.edu/mayo/research/staff/boeve_bf.cfm
My clinical and research interests include normal aging, neurodegenerative disorders that cause cognitive impairment/dementia, neurogenetics, prion disorders, autoimmune/inflammatory encephalopathies, and the neurologically-based sleep disorders. Specific disorders of interest include mild cognitive impairment, Alzheimer's disease, Pick's disease, frontotemporal dementia, Lewy body dementia, corticobasal degeneration, posterior cortical atrophy, Creutzfeldt-Jakob disease, "Hashimoto's encephalopathy," nonvasculitic autoimmune meningoencephalopathies, REM sleep behavior disorder, narcolepsy, and restless legs syndrome/periodic limb movement disorder.
I work with colleagues in the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation, Mayo Sleep Disorders Center, Mayo Institute of Neurodegenerative Diseases, Udall Center for Excellence in Parkinson?s Disease Research, and Mayo Clinic Cancer Center.
For 25 years we have studied the molecular neurobiology, pharmacology, and toxicology of cholinesterases, including the role of these enzymes in normal cholinergic neurotransmission and their involvement in disease. Early on we produced monoclonal antibodies that selectively destroyed cholinergic pathways in rats. That unexpected effect led to a unique animal model, which shed light on the normal workings of the sympathetic nervous system and on neuroimmunology. We now focus on cholinesterases as biological targets of drugs, chemical warfare agents, and pesticides, and also as active participants in neurologic disorders. Our recent data show that acetylcholinesterase can promote deposits of brain amyloid in Alzheimer's disease. Working with other Mayo investigators we designed new anticholinesterases to block this pathologic effect and we created a novel line of transgenic mice to test their therapeutic potential. Our latest work involves molecular modeling and rational mutagenesis to convert cholinesterases themselves into clinically useful agents. This approach has already produced novel enzymes that hydrolyze cocaine fast enough to be candidates for treating drug overdose. Now we are evaluating the possibility that viral gene transfer of these enzymes could suppress psychological and behavioral responses to cocaine. A long-term goal is to develop molecular agents that might aid addicts in drug cessation programs.
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| Jan
C. Buckner, M.D. |
Research interests include: 1.) clinical trials of novel therapies for patients with primary and metastatic brain tumors; 2.) correlative studies to determine the clinical significance of histologic and genetic variables in brain tumor tissue; 3.) pharmacokinetic interactions among antineoplastic and anticonvulsant medications; 4.) neurobehavioral consequences of brain tumors and their treatment; and, 5.) methodologic issues in designing clinical trials for brain tumor patients.
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| James
R. Cerhan, M.D., Ph.D. |
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Cancer etiology, prevention, and control for non-Hodgkin lymphoma, chronic lymphocytic leukemia, prostate, and breast cancer; Molecular and genetic epidemiology.
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| Suresh
T. Chari, M.D. |
Primary Appt:
Gastroenterology
Associate Professor of Medicine
Mayo Clinic College of Medicine
I am a gastroenterologist with broad interest in diseases of the pancreas. My NIH-funded research focuses on the role of diabetes and hyperglycemia as a marker of undiagnosed pancreatic cancer. Majority of patients with pancreatic cancer have hyperglycemia and my research explores the possibility of using this fact to diagnose pancreatic cancer before it becomes symptomatic.I am also part of the Mayo Clinic Pancreas Cancer SPORE.
My areas of clinical research also involves understanding the clinical spectrum of autoimmune pancreatitis. We currently have identified over 50 patients with autoimmune pancreatitis and believe this is more common than previously recognized.
I am also interested in cystic tumors of the pancreas including their classification, prevalence and natural history
See a listing of my publications
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| John
C. Cheville, M.D. |
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My research focuses on urologic malignancies, and the pathologic features predictive of outcome in patients with prostate cancer, renal cell carcinoma, urothelial carcinoma, and testicular tumors. I am responsible for the Mayo Clinic Prostate Cancer SPORE Tissue Core for the collection of fresh and fixed prostate tissues for research; the Prostate SPORE Tissue Core also supports high-throughput tissue microarray construction, laser capture microdissection, immunohistochemistry, and in situ studies.
Dr George K Chow:
I have subspecialty training in laparoscopic urology and endourology. My research interests include working on the surgical robot (DaVinci) and clinical research related to laparoscopic donor nephrectomy, laparoscopic nephroureterectomy and laparoscopic partial nephrectomy. I am interested in ablative techniques (radiofrequency, cryoablation) in the treatment of renal masses.
Jasper R. Daube, M.D. My research interests include:
Our research also collaborates on multicenter trials of therapy for ALS.
Piet C. de Groen, M.D.
My clinical research objective is to decrease the mortality due to hepatocellular
cancer (primary cancer of the liver) and cholangiocarcinoma (cancer of the bile
ducts) by actively pursuing early detection of these diseases in patients at
risk, develop new or improve current diagnostic modalities, and finally
investigate new treatment options.
In addition, I have an interest in bioinformatics. I have led the development of web-based databases and applications for the Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota, and currently am the Program Director at Mayo Clinic Rochester of the Mayo Clinic/IBM Computational Biology Collaboration which is developing a comprehensive prototype system for access to and interpretation of clinical, genomic as well as proteomic data.
A third field of interest combines clinical and informatics research. Together with colleagues from Iowa State University and the University of Texas at Arlington, I am developing computer-based, automated analysis tools for endoscopic procedures. This requires development of new algorithms for analysis of digitized audio-video files; our current focus is colonoscopy. Together with colleagues from the University of Minnesota, I am working on data mining of clinical data in order to determine whether past information can successfully be used to predict future health status outcomes.
See a listing of my publications
Claude Deschamps, M.D.
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| David W. Dodick, M.D. |
Research efforts include the testing of novel compounds for the acute and prevetive treatment of migraine and cluster headache. Also, I am involved in basic studies to determine the underlying central nervous system abnormalities involved in the development of chronic daily headache. In collaboration with colleagues in Neurosurgery and Anasthesia/Pain, we are conducting clinical trials to evaluate the safety and efficacy of peripheral neurostimulation devices for chronic head pain/ chronic migraine. I am also involved in the evaluation of new compounds for the acute treatment of ischemic stroke. The stroke team at MCS is also conducting studies using novel agents for the treatment of acute stroke.
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| William
A. Faubion, M.D. |
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My laboratory focus is primarily on the relationship between cells of the innate immune system, regulatory T cells, and commensal bacteria. We use animal models of inflammatory bowel disease to understand how macrophages and dendritic cells signal regulatory T cells to control chronic gastrointestinal inflammation. We also study the response of human regulatory T cells from patients with inflammatory bowel disease to bacterial products. As our clinical focus is Crohn's disease and ulcerative colitis, we hope our research leads to improved understanding of mechanisms and novel therapy.
See a listing of my publications
My laboratory is interested in the genetics, biochemistry and cell biology of lung and colon cancers and of chronic myelogenous leukemia. We are focusing on the role members of the protein kinase C (PKC) family of protein kinases play in the initiation, promotion and metastatic spread of these cancers. We have developed cell and mouse models to help us understand how specific PKC isozymes are involved in colon and lung carcinogenesis. Our results demonstrate that multiple PKC isozymes paly critical role sin cancer development, or carcinogenesis. We have identified one PKC isozyme, PKCiota, that is required for transformed growth of human lung cancer cells in vitro and human lung cancer tumors grown in nude mice. We have also shown that PKCiota is overxpressed in human lung cancers and predicts poor survivalin patients with lung cancer. Our data demonstrate that PKCiota may be an important prognostic indicator and therapeutic target in lung cancer. My research program is included in the GI Cancer and Pharmacology and Experimental Therapeutics Programs within the Mayo Clinic Comprehensive Cancer Center.
Fitch, Tom R., M.D. Chair Hematology
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| Rafael
Fonseca, M.D. |
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In the laboratory of Dr. Fonseca, we concentrate on the genetic and cytogenetic nature of the clonal cells of the plasma cell disorders. To achieve this, we use a variety of tools: molecular genetics, FISH, PCR, arrays, etc. Our laboratory currently is composed of five full time technologists and three post-doctoral fellows.
Origin of the MGUS clone and genomic instability: We have begun a systematic evaluation of MGUS plasma cells by molecular/cytogenetic methods. Ultimately we want to understand the nature of the clone, clinical and biologic significance of the abnormalities, and order of acquisition of abnormalities. We are also interested in the factors permissive for the significant genomic instability observed in the plasma cell neoplasms.
Progression from MGUS to myeloma: We want to better understand why some MGUS patients progress to MM and why some never do, and which abnormalities are acquired and thus important for disease progression. In the context of a funded SPORE grant we are doing a detailed genetic characterization of the risk of progression in MGUS according to cytogenetic status. We also descibed the presence of these IgH translocations in MGUS cells, even those associated with an aggressive clinical behavior in myeloma. Most recently we have shown the presence of hyperdiploid and Non-hyperdiploidy dichotomy in MGUS.
Clinical significance of chromosomal abnormalities in myeloma: In our lab we study the clinical, biologic, and prognostic implications of specific chromosomal and genetic abnormalities for patients with myeloma. Ultimately, we believe that the accurate knowledge of the abnormalities underlying myeloma will allow for a better management and treatment of patients. For instance we have described the negative impact on prognosis of some genetic aberrations and better outcome with others. Furthermore we have shown different pathology and clinical features of myeloma based on this genetic characterization.
Molecular studies of genetic abnormalities in clonal cells of light-chain amyloidosis: Ultimately, we want to understand the nature of the clone, and its relation to the protein abnormality. We also have interest in the features of the light chains that make them amyloidogenic.
Molecular studies of genetic abnormalities in clonal cells of Waldenstrom macroglobulinemia (WM): Our studies have focused on the genetic abnormalities of clonal cells of patients with macroglobulinemia and their relation to other B-cell malignancies. Our lab described the presence of losses in chormosome 6 in nearly one half of patients with WM. We also showed these cells lack chromosome translocations and never have the t(9;14), resulting in PAX5 upregulation
See a listing of my publications
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| Robert L. Foote, M.D. |
My research interests include treatment of malignant and benign tumors of the head and neck region (including endocrine neoplasms such as thyroid and parathyroid cancer) and skin. This includes evaluating new radiation fractionation schemes, combining radiation therapy with chemotherapy, immunotherapy, gene therapy and other targeted biological agents; and evaluating new technology such as electronic portal imaging devices, stereotactic radiosurgery, intensity modulated radiation therapy, 4-dimensional radiation simulation and treatment, image-guided radiation therapy and proton/heavy ion beam therapy. I also have research interests in the prevention and management of acute and chronic effects of radiation such as mucositis, xerostomia and carotid artery stenosis. Much of research has been conducted in collaboration with the Mayo Cancer Center, North Central Cancer Treatment Group and the Radiation Therapy Oncology Group.
See a listing of my publications
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| Dennis A. Gastineau, M.D. publications on PubMed |
Mucin Glycoproteins in Disease
Our laboratory is interested in the role of mucin glycoproteins in disease. Mucins are large molecular weight (250,000 to > 1 million Daltons) glycoproteins with from 50% to 90% of their molecular mass due to O-linked carbohydrates. Mucins have been incriminated in several diseases, in particular, carcinomas of the mammary gland, lung, colon, pancreas, stomach, prostate, ovary, and endometrium, in which a cell-associated mucin, MUC1, has been shown to be up-regulated and aberrantly expressed. Our primary research goals are: 1) to determine the function of the MUC1 cell-associated mucin molecule in cell adhesion, tumor progression, metastasis, and modulation of the immune system; and 2) to characterize MUC1 immunogens as a tumor vaccines.
Our hypothesis is that over-expression of the MUC1 protein by the cancer cells may confer an advantage upon the cell, perhaps by reducing the adhesive properties of cells and/or by modulating the immunogenicity of the tumor cells. The function of MUC1 may be dependent on its long, rod-like extracellular domain that may affect cell-cell and cell-matrix interactions. However, there is increasing evidence that MUC1 is involved in signal transduction. The cytoplasmic domain is phosphorylated (tyrosines and serines) and binds to proteins capable of transducing signals and/or interacting with the cytoskeleton. We have identified a number of interacting proteins and are presently characterizing the interactions biochemically. To address the function of MUC1 in tumor progression and metastasis, a mouse deficient in MUC1 (designated Muc1 in the mouse) has been created using homologous recombination. Mammary gland tumors were generated in the Muc1-deficient and control animals, using transgenic oncogene-expressing mice. Mammary gland tumors lacking Muc1 protein grew more slowly and metastasized less frequently than tumors expressing Muc1. Over expression of MUC1 in mouse mammary gland elicited mammary tumors, suggesting that MUC1 acts as an oncogene. Mutant forms of MUC1 are also being expressed, which may reveal important domains of the glycoprotein that function in mammary gland development, tumor progression and metastasis.
The ubiquitous and aberrant expression of MUC1 on most solid tumors (adenocarcinomas) suggests that MUC1 may be a potential immunotherapeutic reagent. Studies have shown that MUC1 has the potential to elicit tumor-specific immunity, to protect from tumor occurrence or prevent tumor recurrence. However, expression of MUC1 is not sufficient to stimulate the immune system effectively. There is a need for studies to devise effective presentation of tumor antigens to stimulate immune cells to kill tumor cells. We have developed transgenic mice expressing human MUC1 as a self molecule to provide an appropriate preclinical model. These mice spontaneously develop tumors of either the mammary gland or the pancreas. We are testing powerful new immunization approaches (dendritic cell/tumor cell fusions) to immunize the animals to MUC1 and other tumor antigens. Our goal is the prevention and treatment of spontaneous tumors and metastases of mammary gland and pancreatic tumors. Clinical trials in breast cancer will begin shortly.
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| Joseph
P. Grande, M.D. |
Virtually all forms of progressive renal disease are characterized by excessive deposition of collagen IV. The lack of effective therapies for chronic renal disease are in large part due to a lack of understanding of basic mechanisms of fibrogenesis. Although TGF-beta1 has emerged as a predominant mediator of extracellular matrix production, the intracellular signaling pathways elicited by TGF-beta1 and the mechanism by which TGF-beta1 stimulates transcription of the collagen IV genes in pathophysiologic states is not known. We are currently delineating points of functional crosstalk between the Smad signaling pathways and the MAPK signaling pathways, and how these pathways culinate in transcriptional activation of the collagen IV genes. In parallel studies, we have recently found that agonists of the cAMP-PKA system are effective in inhibiting mesangial cell proliferation and matrix synthesis in response to acute renal injury. We are testing the hypothesis that the cAMP-PKA system may provide negative crosstalk with critical mitogenic, inflammatory, and matrix signaling pathways and may thereby prevent the onset and development of progressive renal disease. In collaboration with the Transplant Center, we are attempting to develop better prognostic markers, which will predict the development of renal fibrosis in allograft recipients.
Greene, Eddie L., M.D. Kidney
Greipp, Philip R., M.D. Blood malignancies
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