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Daniel William Cramer, MD, ScD
Gynecologist, Brigham and Women's Hospital
Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Brigham and Women's Hospital
Department of Obstetrics and Gynecology
75 Francis Street
Boston, MA 02115


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Research Narrative:

For 30 years, I have sought to advance the prevention and early detection of ovarian cancer through epidemiologic and biomarker research and gained a broad vision inter-relating common risk factors for cancer, mucin tumor antigens, and humoral and cellular immune reactions to them. My research suggests ovarian cancer pathogenesis involves acute and chronic events that affect immunity related to the mucin (MUC) family of proteins, CA15.3(MUC1) and CA125(MUC16).  These line epithelial tracts and are over expressed during inflammatory, hormonal, or neoplastic events affecting these tissues.  Acute events like mumps or a tubal ligation release tumor-like MUC1 and MUC16, expose them to the immune system, and create anti-MUC1 or anti-MUC16 antibodies protective against mucin-expressing ovarian cancer.  Chronic events like endometriosis, repeated ovulation, and genital talc use cause persistent exposure to mucins, down regulation of immunity, lower antibody levels, and increased risk for ovarian cancer.  Mucins and immune reaction to them may also explain risk factors common to many different cancers including aging, obesity, smoking, childhood infections, and reproductive events. A major obstacle is a paucity of datasets that allow mucin antigen (or antibody) levels to be examined in the context of the WBC differential count.  When this has been done, the neutrophil-to-lymphocyte ratio (NLR), a biomarker of inflammation, correlates directly with higher tumor stage and grade, higher CA125, and poorer survival.  To move this research forward I received an NCI R35 award which aimed to: 1) assay CA125, CA15.3, anti-CA125 and anti-CA15.3 antibodies in sera from ovarian cancer cases at diagnosis and women from national surveys, both with WBC and risk factor data; 2) develop a novel microscopic assay to quantify binding of CA125 (or CA15.3) to monocytes and qualify their subclass; and 3) study the functional immune effects of CA125-binding to WBCs.  The research involves collaboration with BWH co-investigators, MGH optics, and immunology at MIT.   


Education:
MD
SC.D.

Publications (Pulled from Harvard Catalyst Profiles):

1. McDonald SA, Fan Y, Welch WR, Cramer DW, Godleski JJ. Migration of Talc From the Perineum to Multiple Pelvic Organ Sites. Am J Clin Pathol. 2019 Jul 15.

2. Harris HR, Cushing-Haugen KL, Webb PM, Nagle CM, Jordan SJ, Risch HA, Rossing MA, Doherty JA, Goodman MT, Modugno F, Ness RB, Moysich KB, Kjær SK, Høgdall E, Jensen A, Schildkraut JM, Berchuck A, Cramer DW, Bandera EV, Rodriguez L, Wentzensen N, Kotsopoulos J, Narod SA, McLaughlin JR, Anton-Culver H, Ziogas A, Pearce CL, Wu AH, Lindström S, Terry KL. Association between genetically predicted polycystic ovary syndrome and ovarian cancer: a Mendelian randomization study. Int J Epidemiol. 2019 Jun 18.

3. Grant DJ, Manichaikul A, Alberg AJ, Bandera EV, Barnholtz-Sloan J, Bondy M, Cote ML, Funkhouser E, Moorman PG, Peres LC, Peters ES, Schwartz AG, Terry PD, Wang XQ, Keku TO, Hoyo C, Berchuck A, Sandler DP, Taylor JA, O'Brien KM, Velez Edwards DR, Edwards TL, Beeghly-Fadiel A, Wentzensen N, Pearce CL, Wu AH, Whittemore AS, McGuire V, Sieh W, Rothstein JH, Modugno F, Ness R, Moysich K, Rossing MA, Doherty JA, Sellers TA, Permuth-Way JB, Monteiro AN, Levine DA, Setiawan VW, Haiman CA, LeMarchand L, Wilkens LR, Karlan BY, Menon U, Ramus S, Gayther S, Gentry-Maharaj A, Terry KL, Cramer DW, Goode EL, Larson MC, Kaufmann SH, Cannioto R, Odunsi K, Etter JL, Huang RY, Bernardini MQ, Tone AA, May T, Goodman MT, Thompson PJ, Carney ME, Tworoger SS, Poole EM, Lambrechts D, Vergote I, Vanderstichele A, Van Nieuwenhuysen E, Anton-Culver H, Ziogas A, Brenton JD, Bjorge L, Salvensen HB, Kiemeney LA, Massuger LFAG, Pejovic T, Bruegl A, Moffitt M, Cook L, Le ND, Brooks-Wilson A, Kelemen LE, Pharoah PDP, Song H, Campbell I, Eccles D, DeFazio A, Kennedy CJ, Schildkraut JM. Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women. Cancer Med. 2019 May; 8(5):2503-2513.

4. Sasamoto N, Babic A, Rosner BA, Fortner RT, Vitonis AF, Yamamoto H, Fichorova RN, Tjønneland A, Hansen L, Overvad K, Kvaskoff M, Fournier A, Romana Mancini F, Boeing H, Trichopoulou A, Peppa E, Karakatsani A, Palli D, Pala V, Mattiello A, Tumino R, Grasso CC, Onland-Moret NC, Weiderpass E, Quirós JR, Lujan-Barroso L, Rodríguez-Barranco M, Colorado-Yohar S, Barricarte A, Dorronsoro M, Idahl A, Lundin E, Sartor H, Khaw KT, Key TJ, Muller D, Riboli E, Gunter MJ, Dossus L, Kaaks R, Cramer DW, Tworoger SS, Terry KL. Predicting Circulating CA125 Levels among Healthy Premenopausal Women. Cancer Epidemiol Biomarkers Prev. 2019 Jun; 28(6):1076-1085.

5. Minlikeeva AN, Cannioto R, Jensen A, Kjaer SK, Jordan SJ, Diergaarde B, Szender JB, Odunsi K, Almohanna H, Mayor P, Starbuck K, Zsiros E, Bandera EV, Cramer DW, Doherty JA, DeFazio A, Edwards R, Goode EL, Goodman MT, Høgdall E, Matsuo K, Mizuno M, Nagle CM, Ness RB, Paddock LE, Pearce CL, Risch HA, Rossing MA, Terry KL, Wu AH, Modugno F, Webb PM, Moysich KB. Joint exposure to smoking, excessive weight, and physical inactivity and survival of ovarian cancer patients, evidence from the Ovarian Cancer Association Consortium. Cancer Causes Control. 2019 May; 30(5):537-547.

6. McDonald SA, Fan Y, Welch WR, Cramer DW, Stearns RC, Sheedy L, Katler M, Godleski JJ. Correlative polarizing light and scanning electron microscopy for the assessment of talc in pelvic region lymph nodes. Ultrastruct Pathol. 2019; 43(1):13-27.

7. Kim S, Wang M, Tyrer JP, Jensen A, Wiensch A, Liu G, Lee AW, Ness RB, Salvatore M, Tworoger SS, Whittemore AS, Anton-Culver H, Sieh W, Olson SH, Berchuck A, Goode EL, Goodman MT, Doherty JA, Chenevix-Trench G, Rossing MA, Webb PM, Giles GG, Terry KL, Ziogas A, Fortner RT, Menon U, Gayther SA, Wu AH, Song H, Brooks-Wilson A, Bandera EV, Cook LS, Cramer DW, Milne RL, Winham SJ, Kjaer SK, Modugno F, Thompson PJ, Chang-Claude J, Harris HR, Schildkraut JM, Le ND, Wentzensen N, Trabert B, Høgdall E, Huntsman D, Pike MC, Pharoah PDP, Pearce CL, Mukherjee B. A comprehensive gene-environment interaction analysis in Ovarian Cancer using genome-wide significant common variants. Int J Cancer. 2019 05 01; 144(9):2192-2205.

8. Cramer DW, Elias KM. Perspectives on Ovarian Cancer From SEER: Today and Tomorrow. J Natl Cancer Inst. 2019 Jan 01; 111(1):5-6.

9. Yang Y, Wu L, Shu X, Lu Y, Shu XO, Cai Q, Beeghly-Fadiel A, Li B, Ye F, Berchuck A, Anton-Culver H, Banerjee S, Benitez J, Bjørge L, Brenton JD, Butzow R, Campbell IG, Chang-Claude J, Chen K, Cook LS, Cramer DW, deFazio A, Dennis J, Doherty JA, Dörk T, Eccles DM, Edwards DV, Fasching PA, Fortner RT, Gayther SA, Giles GG, Glasspool RM, Goode EL, Goodman MT, Gronwald J, Harris HR, Heitz F, Hildebrandt MA, Høgdall E, Høgdall CK, Huntsman DG, Kar SP, Karlan BY, Kelemen LE, Kiemeney LA, Kjaer SK, Koushik A, Lambrechts D, Le ND, Levine DA, Massuger LF, Matsuo K, May T, McNeish IA, Menon U, Modugno F, Monteiro AN, Moorman PG, Moysich KB, Ness RB, Nevanlinna H, Olsson H, Onland-Moret NC, Park SK, Paul J, Pearce CL, Pejovic T, Phelan CM, Pike MC, Ramus SJ, Riboli E, Rodriguez-Antona C, Romieu I, Sandler DP, Schildkraut JM, Setiawan VW, Shan K, Siddiqui N, Sieh W, Stampfer MJ, Sutphen R, Swerdlow AJ, Szafron LM, Teo SH, Tworoger SS, Tyrer JP, Webb PM, Wentzensen N, White E, Willett WC, Wolk A, Woo YL, Wu AH, Yan L, Yannoukakos D, Chenevix-Trench G, Sellers TA, Pharoah PDP, Zheng W, Long J. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk. Cancer Res. 2019 02 01; 79(3):505-517.

10. Akinwunmi B, Vitonis AF, Titus L, Terry KL, Cramer DW. Statin therapy and association with ovarian cancer risk in the New England Case Control (NEC) study. Int J Cancer. 2019 03 01; 144(5):991-1000.