Summer 2000 - Research Project

Patrick Stangeby

Patrick is interested in the cellular and molecular aspects of medicine and plans on specializing in pathology or a similar specialty.  He hopes to gain the experience, skills and exposure that may help him in pursuit of a pathology residency.

Title of Project:

Comparative genomic hybridization to determine pattern of genetic alterations in pediatric brain tumors


 

Faculty Mentor:

Adekunle M. Adesina, M.D., Ph.D.

This project is set in the broader context of investigating cell regulatory proteins in a type of pediatric brain tumor called medulloblasotoma. The overall aims are to uncover possible oncogenes and/or tumor suppressor genes that may function in this tumor type and that may lead to innovative gene therapy strategies to treat medulloblastoma. 

In this summer project, genomic DNA will be extracted from both brain tumors and normal tissue of patients. The DNA will be subsequently digested with restriction enzymes and labeled for use as fluorescence probes. These probes will be used to label normal human metaphase chromosomes in fluorescence in situ hybridization (FISH) comparative hybridization (CH) assays.  Complementary sequences of brain tumor probe and normal chromosomal DNA will hybridize with each other while un-hybridized chromosomal sequences will be unlabeled. The resulting karyotypes of the individual tumors will then be analyzed by computer-aided image analysis for any consistencies in the hybridization pattern which may indicate chromosomal deletion sites.  Such common sites of deletion may then be further investigated as possible loci of tumor suppressor genes whose absence allows tumor formation.


Jeffrey Fanning

Jeffrey is interested in pursuing an area of medicine that will provide him the opportunity to maintain a balance between research, academia, and clinical practice throughout his career.   He sees a career in Pathology as a means to achieve this.  Jeffrey has a strong interest in neurosciences and has chosen to work on a research project related to Alzheimer's disease.

Title of Project:

Immunohistochemical characterization of Alzheimer's versus non-Alzheimer's type dementia


 

Faculty Mentor:

Roger A. Brumback, M.D.

Dementia, of which Alzheimer's type is most prevalent, effects 6% of individuals over 65 years of age; and with the increasing percentage of people aged over 65 it seems imperative that research related to Alzheimer's should  not only continue but increase.  The following research is important not only to the medical community but also to the medical education process as it incorporates both basic science and applied research with various disciplines such as Pathology, Physiology, Biochemistry, and Neuroscience.  In addition, Alzheimer's disease and related dementia are diseases which future physicians will most certainly see in their medical practice and will likely see with increasing frequency in the new millennium. 

The proposed research is based primarily on two articles regarding the  neuropathological stages and histopathologic diagnosis of Alzheimer's disease.  Braak and Braak (1991) characterized six stages of Alzheimer's disease by comparing brain autopsies from 83 demented and non-demented individuals.  The results showed that a qualitative evaluation of a few key preparations using a Bielchowsky silver staining procedure was required for the differentiation of each stage.  In 1993 Mira, Hart, and Terry described a procedure for the diagnosis for Alzheimer's disease based on information provided to them by physicians participating in CERAD, the Consortium for Establishing a Registry for Alzheimer's Disease.  Results, also obtained using a Bielchowsky silver staining method, were used to develop a protocol to make differential diagnoses of Alzheimer's and related dementia.  The current research will use these protocols : 1) to make differential diagnoses of Alzheimer's-type dementia, non-Alzheimer's type dementia (Pick's disease and Lewy Body disease) and non-demented individuals, and 2) to characterize the various stages of Alzheimer's disease in 150 autopsied brain specimens.  The differential diagnosis and neuropathological staging of Alzheimer's disease will be re-evaluated using a 3x(3) mixed model design and current immunohistochemical procedures regarding proteins characteristic of Alzheimer's, Pick's, and Lewy Body type dementia (b-amyloid, Tau, and a-synuclein).  This information will be used in conjunction with that gathered using the older silver staining method.  This research will hopefully help provide more accurate and specific information needed in performing diagnoses of Alzheimer's and related dementia.  In addition it will be another step in attempting to discern the pathogenesis of this deadly and debilitating disease.