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CURRICULUM VITAE Name: Gerald Angus James McIndoe Date of Birth: 24 August 1955 Address: Department of Obstetrics and Gynaecology Hammersmith Hospital Du Cane Road London W12 0HS Telephone: +44 (0)20 8383 3268 Fax: +44 (0)20 8383 8065 Present Appointment: Consultant in Gynaecological Oncology Hammersmith Hospitals NHS Trust RCOG Accreditation: General accreditation in Obstetrics and Gynaecology Subspecialist accreditation in Gynaecological Oncology Qualifications: Societies: BSc Auckland 1974 MB ChB Auckland 1980 FRCS England 1985 MRCOG London 1987 PhD London 1993 British Medical Association British Society for Colposcopy and Cervical Pathology British Gynaecological Cancer Society Royal Society of Medicine PREVIOUS APPOINTMENTS Saint Mary's Hospital - Addenbrooke's Hospital Senior Registrar Rotation Jan 1993 - Oct 1994 Senior Registrar in Obstetrics and Gynaecology Addenbrooke's NHS Trust Rosie Maternity Hospital, Cambridge Jan 1991 - Dec 1992 RCOG approved Subspecialty Trainee in Gynaecological Oncology Hammersmith Hospital London and St Mary's Hospital London Clinical Research Fellow (Prof PCL Beverley) Human Tumour Immunology Group, Imperial Cancer Research Fund, London May 1987 - March 1988 Registrar in Obstetrics and Gynaecology St Mary's Hospital London July 1985 - Dec 1986 Registrar in Obstetrics and Gynaecology (Rotating position) National Women's Hospital Auckland, New Zealand June 1982 - May 1983 SHO in Obstetrics and Gynaecology Whittington Hospital London Jan 1984 - June 1985 Registrar in General Surgery (Mr BL Dowling) Northampton General Hospital, Northampton Aug 1983 - Jan 1984 SHO in General Surgery (Miss AO Mansfield) Royal Postgraduate Medical School Hammersmith Hospital London House Officer Cook Hospital Gisborne, New Zealand Research Training April 1988 - Dec 1990 Obstetrics and Gynaecology General Surgery Pre-registration Training Dec 1980 - Nov 1981 PhD Thesis: Cell mediated immune response to HPV 16 I was employed on a clinical research fellowship by the Imperial Cancer Research Fund. Under Professor Peter Beverley, I investigated the role of the cellular immune system in modulating the natural history of human papillomavirus (HPV) infection and neoplasia of the cervix. This work has been accepted as a PhD by the University of London. Initial experiments used synthetic peptides from the L1 and E6 open reading frames (ORFs) of HPV 16, identified on the basis of the Rothbard and Taylor predictive algorithm, as antigen in studies of proliferation of PBMC to HPV antigens. DR restriction of these peptide determinants was mapped using transfected L cells, and homologous peptides from other HPV types were tested for their ability to stimulate PBMC and T cell lines. These peptides were used to assay proliferative responses in patients with premalignant and malignant disease associated with HPV 16. Preliminary results suggested that patients with advanced disease responded more strongly to these antigens. To identify cytotoxic T lymphocytes (CTL) directed against HPV 16 antigens, cells expressing HPV 16 proteins and appropriate MHC molecules are required. The traditional approach is to use autologous antigen presenting cells infected with the virus, but since infectious virus is not available, a variety of alternative stimulators were generated using molecular biological techniques. These included murine tumour cell lines expressing transfected HLA genes and HPV ORFs, recombinant HPV-vaccinia virus constructs to infect autologous antigen presenting cells, and established cervical tumour cell lines with HLA matched donors. For a variety of different reasons, none of these approaches were successful. As an alternative approach, keratinocytes were tested for their ability to present antigen to both class I and class II restricted T cells. Antigen was presented poorly to class I restricted T cells but keratinocytes expressing class II were unable to induce proliferation of an influenza HA-specific, DR4 restricted human T cell clone. Co-culture of the clone with HA peptide and IFN treated keratinocytes did not simply fail to cause T cell proliferation, rather a state of anergy resulted whose induction was antigen specific and DR restricted. Because of the difficulties in identifying human CTL responses, a mouse model was developed with a view to returning to the human system when suitable stimulators had been identified. In this model, HPV 16 L1 and E7 specific CTL were identified, and the determinants were mapped using synthetic peptides. Recombinant vaccinia virus constructs expressing L1 and E7 were shown to prime HPV 16 specific CTL in the mouse, and were also shown to boost CTL responses in vitro. These constructs are likely to be suitable as stimulators of human CTL. PUBLICATIONS deSouza NM, Dina R, McIndoe GA, Soutter WP. Cervical cancer: value of an endovaginal coil magnetic resonance imaging technique in detecting small volume disease and assessing parametrial extension. Gynecol Oncol. 2006; 102: 80-5. Saini A, Dina R, McIndoe GA, Soutter WP, Gishen P, deSouza NM. Characterization of adnexal masses with MRI. Am J Roentgenol 2005; 184: 1004-9. deSouza NM, O'Neill R, McIndoe GA, Dina R, Soutter WP. Borderline tumors of the ovary: CT and MRI features and tumor markers in differentiation from stage I disease. Am J Roentgenol 2005; 184: 999-1003. Mahon MM, deSouza NM, Dina R, Soutter WP, McIndoe GA, Williams AD, Cox IJ. Preinvasive and invasive cervical cancer: an ex vivo proton magic angle spinning magnetic resonance spectroscopy study. NMR Biomed 2004; 17: 144-53. Nicholson S, Bomphray CC, Thomas H, McIndoe A, Barton D, Gore M, George AJT. A phase I trial of idiotypic vaccination with HMFG1 in ovarian cancer. Cancer Immunol Immunother 2004; 53: 809-16. SoutterWP, Hanoch J, D'Arcy T, Dina R, McIndoe GA, deSouza NM. Pre-treatment tumour volume measurement on high-resolution magnetic resonance imaging as a predictor of survival in cervical cancer. BJOG 2004; 111: 741-7. Mahon MM, Cox IJ, Dina R, Soutter WP, McIndoe GA, Williams AD, deSouza NM. 1H Magnetic Resonance Spectroscopy of preinvasive and invasive cervical cancer: in vivo - ex vivo profiles and effect of tumor load. JMRI 2004; 19: 35-64. deSouza NM, Soutter WP, Rustin G, Mahon MM, Jones B, Dina R, McIndoe GA. Use of neoadjuvant chemotherapy prior to radical hysterectomy in cervical cancer: monitoring tumour shrinkage and molecular profile on magnetic resonance and assessment of 3-year outcome. Br J Cancer 2004; 90: 2326-31. Diac M, Hanoch J, McIndoe A, Dina R. Keratin induced granulomatous disease of the vagina mimicking a malignant tumour. BJOG 2004; 111: 389-90. Mahon MM, Williams AD, Soutter WP, Cox IJ, McIndoe GA, Coutts GA, Dina R, deSouza NM. 1H Magnetic Resonance Spectroscopy of invasive cervical cancer: an in vivo study with ex vivo corroboration. NMR in Biomedicine 2004; 17: 1-9. Connors A, deSouza NM , McIndoe GA. Adenomyoma mimicking an aggressive uterine neoplasm on MRI. Br J Radiol 2003; 76: 66-68. Gornall RJ, Standfield N, deSouza NM, Aachi VR, McIndoe GA. Resection of recurrent bulky gynaecological side wall malignancy with iliac vessel reconstruction. BJOG 2001; 108: 1305-8. Soutter WP, Haidopoulos D, Gornall RJ, McIndoe GA, Fox J, Mason WP, Flanagan A, Nicholas N, Barker F, Abrahams J, Lampert I, Sarhanis P. Is conservative treatment for adenocarcinoma in situ of the cervix safe? BJOG 2001; 108: 1184-9. Williams AD, Cousins C, Soutter WP, Mubashar M, Peters AM, Dina R, Fuchsel F, McIndoe GA, deSouza NM. Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography. Am J Roentgenol 2001; 177: 343-8. deSouza NM, Whittle M, Williams AD, Sohail M, Krausz T, Gilderdale DJ, McIndoe GA, Soutter WP. Magnetic resonance imaging of the primary site in stage I cervical carcinoma: A comparison of endovaginal coil with external phased array coil techniques at 0.5T. Journal of Magnetic Resonance Imaging. 2000; 12: 1020-6. D'Arcy TJ, Roy A, Thomas A, McIndoe A, Soutter WP. Standards for the management of cervical and vulval carcinoma. British Journal of Obstetrics & Gynaecology 2000; 107: 8468. Panoskaltsis TA, Moore DA, Haidopoulos DA, McIndoe AG. Tuberculous peritonitis: part of the differential diagnosis in ovarian cancer. Am J Obstet Gynecol 2000; 182: 740-2. Basu PS, D’Arcy T, McIndoe A, Soutter WP. Is needle diathermy excision of the transformation zone a better treatment for cervical intraepithelial neoplasia than large loop excision? Lancet 1999; 353: 1852-3. deSouza NM, McIndoe GA, Soutter WP, Krausz T, Chui KM, Hughes C, Mason WP. Value of magnetic resonance imaging with an endovaginal receiver coil in the pre-operative assessment of Stage I and IIa cervical neoplasia. British Journal of Obstetrics & Gynaecology. 1998; 105: 500-7. deSouza NM, Soutter WP, McIndoe GA, Gilderdale DJ, Krausz T. Stage I cervical cancer: tumor volume by magnetic resonance imaging of screen-detected versus symptomatic lesions. Journal of the National Cancer Institute. 1997; 89: 1314-5. Tarpey I, Stacey SN, McIndoe A, Davies DH. Priming in vivo and quantification in vitro of class I MHC-restricted cytotoxic T cells to human papilloma virus type 11 early proteins (E6 and E7) using immunostimulating complexes (ISCOMs). Vaccine 1996; 14: 230-6. Tarpey I, Stacey S, Hickling J, Birley HDL, Renton A, McIndoe A, Davies DH. Human cytotoxic T lymphocytes stimulated by endogenously processed human papillomavirus type 11 E7 recognize a peptide containing a HLA-A2 (A*0201) motif. Immunol. 1994; 81: 222-7. Davies DH, Tarpey I, Stacey S, Hickling J, Bartholomew J, Birley H, Renton A, McIndoe A. Human cytotoxic T cell epitopes in HPV 11: relationships between allele-specific motifs, HLA binding, and stimulation in vitro. Proceedings of the 2nd Intl. Wrkshp of Immunol. of HPV Infections, Cambridge June 1993. Yahya AA. McIndoe GA. Mason WP. Analysis and outcome of 502 cases of laser excision cone (LEC) at the Samaritan Hospital for Women, London. Asia-Oceania J Obstet Gynaecol 1992; 18: 315-8. Zhou J, McIndoe GAJ, Davies HD, Sun X-Y, Crawford L. The induction of cytotoxic T cells by recombinant vaccinia viruses expressing human papillomavirus type 16 L1. Virol 1991; 181: 203-10. Davies HD, McIndoe GAJ, Chain BM: Cancer of the cervix: prospects for immunological control. Br J Exp Pathol 1991; 72: 239-51. Dent CL. McIndoe GA. Latchman DS. The constitutively expressed octamer binding protein OTF-1 and a novel octamer binding protein expressed specifically in cervical cells bind to an octamer-related sequence in the human papillomavirus 16 enhancer. Nucleic Acids Research. 1991; 19: 4531-5. Bal V, McIndoe A, Denton G, Hudson D, Lombardi G, Lamb J and Lechler R: Antigen presentation by keratinocytes induces tolerance in human T cells. Eur J Immunol 1990; 20: 1893-7. Strang G, Hickling JK, McIndoe GAJ, Howland K, Wilkinson D, Ikeda H and Rothbard JB: Human T cell responses to human papillomavirus type 16 L1 and E6 synthetic peptides: Identification of T cell determinants, HLA-DR restriction and virus type specificity. J Gen Virol 1990; 71: 423-31. Greco A, Mason P, Leung AWL, Dische S, McIndoe GAJ and Anderson MC: Staging of carcinoma of the uterine cervix: MRI - surgical correlation. Clin Radiol 1989; 40: 401-5. McIndoe GAJ, Smith R, Tidy JA, Yayah A, Mason WP, Anderson MC: Occult cervical carcinoma revealed by large loop diathermy. Lancet 1989; ii: 807. McIndoe GAJ, Robson MS, Tidy JA, Mason WP and Anderson MC: Laser excision rather than vaporization: the treatment of choice for cervical intraepithelial neoplasia. Obstet Gynecol 1989; 74: 165-8. McIndoe GAJ, Jones RW and Grieve B: The Aldridge sling procedure in the treatment of urinary stress incontinence. Aust NZ J Obstet Gynaecol 1987; 27: 238-9. Salem RR, McIndoe GAJ, Matkin JA, Lidou ACM and Wood CB: The haematologic effects of Latamoxef Sodium when used as a prophylaxis during surgical treatment. Surg Obstet Gynecol 1987; 164: 525-9. McIndoe GAJ and Hopkins NFG: "Spontaneous" rupture of the diaphragm. Postgrad Med J 1986; 62: 389-91. McIndoe GAJ, Menzies KW and Reddy J: Sulindac (Clinoril) and cholestatic jaundice. NZ Med J1981; 94: 430-1.