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Educational Background
Medical/Graduate Education
| 1974 |
M.D. |
University of Virginia School of Medicine |
Post-doctoral Fellowship(s)
| 1974-1975 |
Internship in Medicine |
University of South Carolina |
| 1975-1979 |
Residency in Pathology |
University of Virginia |
| 1979-1981 |
Fellowship in Pathology |
Columbia University College of Physicians and Surgeons |
Board Certification
Academic Interest(s)
Vulvar and Cervical Pathology, Tubo-ovarian Carcinogenesis
Dr. Crum conducts translational and collaborative studies in several areas of investigation.
1) Markers of lower genital tract neoplasia: This work has three components. The first is the validation of surrogate markers for HPV infection identified in the laboratory (Cyclin E) or by others (p16, Mib-1). The second is collaborative studies with industry (Ventana Medical Systems Inc) designed to produce more sensitive assays for in situ HPV nucleic acid detection (ISH) in the cervix and lower genital tract. In these studies our laboratory selects the cases, verifies their HPV status by polymerase chain reaction and runs the automated ISH. The third is an ongoing collaborative study, in which Dr. Crum’s laboratory has provided tissues to the Howley laboratory for serial analysis of gene expression (SAGE). In the current study, the Crum laboratory will identify suitable target tissues and analyze them for expression of candidate genes by automated RNA-RNA in situ hybridization.
2) Pathobiology of p63 expression in the genital tract and squamous mucosa: This is an ongoing collaboration between the Crum laboratory and the McKeon lab, and entails the interplay of both laboratories in several projects. The first is an analysis by the McKeon laboratory of p63 expression in cutaneous development in which Dr. Crum provides target tissues and analyzes them using a panel of antibodies provided by the McKeon laboratory. The second is an ongoing collaboration between the McKeon group Dr. Crum and Dr. Elvin (recent clinical fellow in W&P pathology) analyzing the role of p63 in germ cell development. This work has entailed analysis of human and mouse tissues for expression of a range of genes associated with germ cell maturation and comparisons between these genes and p63. In third project has been to profile the development and evolution of cervical reserve cells using models of glandular proliferation. The latter have involved analysis of both mouse embryos and adult human tissues (Ince et al, 2002; Witkiewicz et al 2005).
3) Immunotherapeutics in the management of early cervical neoplasia: This is a long-term and on-going collaboration between the Crum laboratory and MGI (formerly Zycos Pharmaceuticals) involving clinical trials designed to determine the safety and efficacy of a DNA vaccine Zyc101a in the management of early cervical neoplasia. Dr. Crum performed all HPV and pathologic studies for the trial and formulated a testing protocol designed to ascertain the dynamics of HPV infection during treatment (Crum et al 2004;Garcia et al 2004). A follow-up study is in progress and Dr. Crum is the PI for the pathology and HPV testing core.
4) Spectroscopic signatures of cervical neoplasia: This is an NIH funded collaboration with the group at the Harrison Spectroscopic Laboratory (Michael Feld) in which Dr. Crum is a site PI at Brigham and Women’s Hospital. With Dr. Crum’s assistance, the Feld group has been able to install a spectroscopic machine in the Women’s and Perinatal Division for the analysis of cervical tissues (ex vivo)(Badizadegan et al, 2004). The ultimate goal is to identify specific spectroscopic signatures of early cervical neoplasia.
5) The tubal fimbria and its role in the pathogenesis of pelvic serous carcinoma: This is the most recent collaborative study initiated by the Crum laboratory. Recognizing that BRCA+ women are at risk for both tubal and ovarian cancer, we are testing the hypothesis that the most lethal form of “ovarian” cancer – ovarian surface or peritoneal serous carcinoma – originates from the tubal fimbria. To do so, Dr. Crum developed a protocol for sectioning and extensively sectioning the fimbriated end (SEE-FIM). Initial studies of BRCA+ women indicate that the majority of cancers detected in prophylactic adnexectomy specimens originate from this location (Medeiros et al, in press 2005). We have identified putative precursors to these early cancers and are applying this protocol in a prospective fashion to all ovarian tumors. In collaboration with Drs. Drapkin and colleagues at the Dana Farber Cancer Institute we are running comparative analyses of these disparate epithelial alterations adjacent to cancers to determine if the tumors are originating from the fimbria. This work has been adopted by the existing ovarian SPORE (Daniel Cramer PI), allocated funding, and has generated several related collaborations between the Crum laboratory and the Division of Gynecologic Oncology.
Publication List and Abstracts (from PubMed/National Library of Medicine)
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