Photo of Bo R. Rueda,  PhD

Bo R. Rueda, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-2825
Fax: (617) 726-0561


brueda@mgh.harvard.edu

Bo R. Rueda, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School
  • Director, Vincent Center for Reproductive Biology, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

My laboratory is actively engaged in basic, translational and clinical research focused in the field of women’s reproductive health. From the oncology perspective, my group molecularly interrogates gynecologic tumors to identify novel cell signaling pathways that contribute to malignant transformation, the pathology of the disease, recurrence and resistance to therapy. Once key factors or pathways are identified, we actively test novel anti-cancer drugs to determine their efficacy in tumor explant models. In addition to my role as a scientist, I am the Executive Director of the MGH Gyn Tissue Repository. The repository infrastructure is extensive and is designed to collect malignant and benign tissues along with clinically annotated information. To complement the banking efforts I have developed a Bio-Banking infrastructure. To this end we utilize a well-established in vivo experimental system in which primary tumors collected from endometrial and ovarian cancer patients at the time of initial surgery are grown in NOD/SCID mice. These explanted tumors and the primary tumors are genotyped and undergo cryopreservation using state of the art techniques. Once thawed, the tumors can be propagated in vivo through serial transplantation over several passages while retaining their original genotype and histophenotype. This allows for the generation of large cohorts of mice hosting matched xenograft tumors ready for use in multi-armed therapeutic experiments. Our work to date provides evidence to suggest the clinical course of the primary tumor mimics the behavior and responses we have seen in our explants further supporting the potential clinical utility of our xenograft model. This model is especially important for our proposed studies with whereby we are investigating the genetic and protein pathways contributing to the resistance to PI3K and HER signaling pathway inhibition using high throughput molecular analyses. It is believed the data generated from our investigations will directly inform the design of future combination trials in advanced gynecologic cancers.

Publications

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  • Roussel-Gervais A, Couture C, Langlais D, Takayasu S, Balsalobre A, Rueda BR, Zukerberg LR, Figarella-Branger D, Brue T, Drouin J. The Cables1 Gene in Glucocorticoid Regulation of Pituitary Corticotrope Growth and Cushing Disease. J Clin Endocrinol Metab 2016; 101:513-22. PubMed
  • Clark NC, Friel AM, Pru CA, Zhang L, Shioda T, Rueda BR, Peluso JJ, Pru JK. Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors. Cancer Biol Ther 2016. PubMed
  • Styer AK, Rueda BR. The Epidemiology and Genetics of Uterine Leiomyoma. 2016. PubMed
  • Hernandez SF, Vahidi NA, Park S, Weitzel RP, Tisdale J, Rueda BR, Wolff EF. Characterization of extracellular DDX4- or Ddx4-positive ovarian cells. Nat Med 2015; 21:1114-6. PubMed
  • Diver EJ, Foster R, Rueda BR, Growdon WB. The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer. Oncologist 2015. PubMed
  • Growdon WB, Groeneweg J, Byron V, DiGloria C, Borger DR, Tambouret R, Foster R, Chenna A, Sperinde J, Winslow J, Rueda BR. HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant. Gynecol Oncol 2015; 137:160-6. PubMed
  • Friel AM, Zhang L, Pru CA, Clark NC, McCallum ML, Blok LJ, Shioda T, Peluso JJ, Rueda BR, Pru JK. Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors. Cancer Lett 2014. PubMed
  • Ince TA, Sousa AD, Jones MA, Harrell JC, Agoston ES, Krohn M, Selfors LM, Liu W, Chen K, Yong M, Buchwald P, Wang B, Hale KS, Cohick E, Sergent P, Witt A, Kozhekbaeva Z, Gao S, Agoston AT, Merritt MA, Foster R, Rueda BR, Crum CP, Brugge JS, Mills GB. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours. Nat Commun 2015; 6:7419. PubMed
  • Groeneweg JW, Hernandez SF, Byron VF, DiGloria CM, Lopez H, Scialabba V, Kim M, Zhang L, Borger DR, Tambouret R, Foster R, Rueda BR, Growdon WB. Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts. Clin Cancer Res 2014. PubMed
  • Doyle JO, Lee HJ, Selesniemi K, Styer AK, Rueda BR. The impact of vitrification on murine germinal vesicle oocyte In vitro maturation and aurora kinase A protein expression. J Assist Reprod Genet 2014. PubMed
  • Clark RM, Lynch MP, Kolp R, Zukerberg LR, Growdon WB, Rueda BR. The N-methyl-D-aspartate receptor, a precursor to N-methyl-D-aspartate receptor encephalitis, is found in the squamous tissue of ovarian teratomas. Int J Gynecol Pathol 2014; 33:598-606. PubMed
  • Stanic AK, Kim M, Styer AK, Rueda BR. Dendritic cells attenuate the early establishment of endometriosis-like lesions in a murine model. Reprod Sci 2014. PubMed
  • Attaman JA, Stanic AK, Kim M, Lynch MP, Rueda BR, Styer AK. The anti-inflammatory impact of omega-3 polyunsaturated Fatty acids during the establishment of endometriosis-like lesions. Am J Reprod Immunol 2014. PubMed
  • Groeneweg JW, Hall TR, Zhang L, Kim M, Byron VF, Tambouret R, Sathayanrayanan S, Foster R, Rueda BR, Growdon WB. Inhibition of gamma-secretase activity impedes uterine serous carcinoma growth in a human xenograft model. Gynecol Oncol 2014. PubMed
  • Bradford LS, Rauh-Hain A, Clark RM, Groeneweg JW, Zhang L, Borger D, Zukerberg LR, Growdon WB, Foster R, Rueda BR. Assessing the efficacy of targeting the phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway in endometrial cancer. Gynecol Oncol 2014; 133:346-52. PubMed
  • Wang L, Gala M, Yamamoto M, Pino MS, Kikuchi H, Shue DS, Shirasawa S, Austin TR, Lynch MP, Rueda BR, Zukerberg LR, Chung DC. Adrenomedullin is a therapeutic target in colorectal cancer. Int J Cancer 2014; 134:2041-50. PubMed
  • Karmon AE, Cardozo ER, Rueda BR, Styer AK. MicroRNAs in the development and pathobiology of uterine leiomyomata: does evidence support future strategies for clinical intervention? Hum Reprod Update 2014. PubMed
  • Fallon EM, Nehra D, Carlson SJ, Brown DW, Nedder AP, Rueda BR, Puder M. Evaluation of anastomotic strength and drug safety after short-term sunitinib administration in rabbits. J Surg Res 2014; 187:101-6. PubMed
  • Groeneweg JW, DiGloria CM, Yuan J, Richardson WS, Growdon WB, Sathyanarayanan S, Foster R, Rueda BR. Inhibition of notch signaling in combination with Paclitaxel reduces platinum-resistant ovarian tumor growth. 2014; 4:171. PubMed
  • Groeneweg JW, Foster R, Growdon WB, Verheijen RH, Rueda BR. Notch signaling in serous ovarian cancer. 2015; 7:95. PubMed
  • Pavlides SC, Huang KT, Reid DA, Wu L, Blank SV, Mittal K, Guo L, Rothenberg E, Rueda B, Cardozo T, Gold LI. Inhibitors of SCF-Skp2/Cks1 E3 ligase block estrogen-induced growth stimulation and degradation of nuclear p27kip1: therapeutic potential for endometrial cancer. Endocrinology 2013; 154:4030-45. PubMed
  • Kulkarni-Datar K, Orsulic S, Foster R, Rueda BR. Ovarian tumor initiating cell populations persist following paclitaxel and carboplatin chemotherapy treatment in vivo. Cancer Lett 2013; 339:237-46. PubMed
  • Foster R, Buckanovich RJ, Rueda BR. Ovarian cancer stem cells: working towards the root of stemness. Cancer Lett 2013. PubMed
  • Arnason T, Pino MS, Yilmaz O, Kirley SD, Rueda BR, Chung DC, Zukerberg LR. Cables1 is a tumor suppressor gene that regulates intestinal tumor progression in Apc(Min) mice. Cancer Biol Ther 2013; 14:672-8. PubMed
  • Rueda BR, Davis JS. No REST for fibroids. Proc Natl Acad Sci U S A 2013; 110:1980-1. PubMed
  • Nehra D, Le HD, Fallon EM, Carlson SJ, Woods D, White YA, Pan AH, Guo L, Rodig SJ, Tilly JL, Rueda BR, Puder M. Prolonging the female reproductive lifespan and improving egg quality with dietary omega-3 fatty acids. Aging Cell 2012. PubMed
  • Fallon EM, Nehra D, Carlson SJ, Potemkin AK, Mitchell PD, Nedder AP, Rueda BR, Puder M. Sunitinib reduces recurrent pelvic adhesions in a rabbit model. J Surg Res 2012; 178:860-5. PubMed
  • Burgos-Ojeda D, Rueda BR, Buckanovich RJ. Ovarian cancer stem cell markers: prognostic and therapeutic implications. Cancer Lett 2012. PubMed
  • Fallon EM, Nehra D, Le HD, Nedder AP, Guo L, Mitchell PD, Rueda BR, Puder M. Effect of sunitinib on functional reproductive outcome in a rabbit model. Fertil Steril 2012; 98:496-502. PubMed
  • Gillet JP, Calcagno AM, Varma S, Davidson B, Bunkholt Elstrand M, Ganapathi R, Kamat AA, Sood AK, Ambudkar SV, Seiden MV, Rueda BR, Gottesman MM. Multidrug resistance-linked gene signature predicts overall survival of patients with primary ovarian serous carcinoma. Clin Cancer Res 2012; 18:3197-206. PubMed
  • Pant A, Lee II, Lu Z, Rueda BR, Schink J, Kim JJ. Inhibition of AKT with the orally active allosteric AKT inhibitor, MK-2206, sensitizes endometrial cancer cells to progestin. PLoS ONE 2012; 7:e41593. PubMed
  • Engler DA, Gupta S, Growdon WB, Drapkin RI, Nitta M, Sergent PA, Allred SF, Gross J, Deavers MT, Kuo WL, Karlan BY, Rueda BR, Orsulic S, Gershenson DM, Birrer MJ, Gray JW, Mohapatra G. Genome wide DNA copy number analysis of serous type ovarian carcinomas identifies genetic markers predictive of clinical outcome. PLoS ONE 2012; 7:e30996. PubMed
  • Gillet JP, Calcagno AM, Varma S, Marino M, Green LJ, Vora MI, Patel C, Orina JN, Eliseeva TA, Singal V, Padmanabhan R, Davidson B, Ganapathi R, Sood AK, Rueda BR, Ambudkar SV, Gottesman MM. Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance. Proc Natl Acad Sci U S A 2011; 108:18708-13. PubMed
  • Growdon WB, Roussel BN, Scialabba VL, Foster R, Dias-Santagata D, Iafrate AJ, Ellisen LW, Tambouret RH, Rueda BR, Borger DR. Tissue-specific signatures of activating PIK3CA and RAS mutations in carcinosarcomas of gynecologic origin. Gynecol Oncol 2011; 121:212-7. PubMed
  • Groeneweg JW, White YA, Kokel D, Peterson RT, Zukerberg LR, Berin I, Rueda BR, Wood AW. cables1 is required for embryonic neural development: molecular, cellular, and behavioral evidence from the zebrafish. 2011; 78:22-32. PubMed
  • Curley MD, Garrett LA, Schorge JO, Foster R, Rueda BR. Evidence for cancer stem cells contributing to the pathogenesis of ovarian cancer. Front Biosci 2011; 16:368-92. PubMed
  • McCann CK, Growdon WB, Kulkarni-Datar K, Curley MD, Friel AM, Proctor JL, Sheikh H, Deyneko I, Ferguson JA, Vathipadiekal V, Birrer MJ, Borger DR, Mohapatra G, Zukerberg LR, Foster R, Macdougall JR, Rueda BR. Inhibition of Hedgehog signaling antagonizes serous ovarian cancer growth in a primary xenograft model. PLoS ONE 2011; 6:e28077. PubMed
  • Groeneweg JW, White YA, Kokel D, Peterson RT, Zukerberg LR, Berin I, Rueda BR, Wood AW. cables1 is required for embryonic neural development: molecular, cellular, and behavioral evidence from the zebrafish. 2010. PubMed
  • Sullivan BT, Cherry JA, Sakamoto H, Henkes LE, Townson DH, Rueda BR. Cytokeratin 18 expression inhibits cytokine-induced death of cervical cancer cells. Int J Gynecol Cancer 2010; 20:1474-81. PubMed
  • Cramer DW, Vitonis AF, Welch WR, Terry KL, Goodman A, Rueda BR, Berkowitz RS. Correlates of the preoperative level of CA125 at presentation of ovarian cancer. Gynecol Oncol 2010; 119:462-8. PubMed
  • Ibrahim N, He L, Leong CO, Xing D, Karlan BY, Swisher EM, Rueda BR, Orsulic S, Ellisen LW. BRCA1-associated epigenetic regulation of p73 mediates an effector pathway for chemosensitivity in ovarian carcinoma. Cancer Res 2010; 70:7155-65. PubMed
  • Wang N, Guo L, Rueda BR, Tilly JL. Cables1 protects p63 from proteasomal degradation to ensure deletion of cells after genotoxic stress. EMBO Rep. 2010; 11:633-9. PubMed
  • Arvisais E, Hou X, Wyatt TA, Shirasuna K, Bollwein H, Miyamoto A, Hansen TR, Rueda BR, Davis JS. Prostaglandin F2alpha represses IGF-I-stimulated IRS1/phosphatidylinositol-3-kinase/AKT signaling in the corpus luteum: role of ERK and P70 ribosomal S6 kinase. Mol Endocrinol 2010; 24:632-43. PubMed
  • Lee HJ, Elmoazzen H, Wright D, Biggers J, Rueda BR, Heo YS, Toner M, Toth TL. Ultra-rapid vitrification of mouse oocytes in low cryoprotectant concentrations. Reprod Biomed Online 2010; 20:201-208. PubMed
  • Friel AM, Zhang L, Curley MD, Therrien VA, Sergent PA, Belden SE, Borger DR, Mohapatra G, Zukerberg LR, Foster R, Rueda BR. Epigenetic regulation of CD133 and tumorigenicity of CD133 positive and negative endometrial cancer cells. Reprod. Biol. Endocrinol. 2011; 8:147. PubMed
  • Friel AM, Growdon WB, McCann CK, Olawaiye AB, Munro EG, Schorge JO, Castrillon DH, Broaddus RR, Rueda BR. Mouse models of uterine corpus tumors: clinical significance and utility. Front Biosci (Elite Ed) 2010; 2:882-905. PubMed
  • Rueda BR, Tilly JL, Schorge JO. Surgical debulking before or after chemotherapy: stemming the tide on ovarian cancer recurrence. Onkologie 2010; 33:286-7. PubMed
  • Curley MD, Therrien VA, Cummings CL, Sergent PA, Koulouris CR, Friel AM, Roberts DJ, Seiden MV, Scadden DT, Rueda BR, Foster R. CD133 expression defines a tumor initiating cell population in primary human ovarian cancer. Stem Cells 2010; 27:2875-83. PubMed
  • Hubbard SA, Friel AM, Kumar B, Zhang L, Rueda BR, Gargett CE. Evidence for cancer stem cells in human endometrial carcinoma. Cancer Res 2009; 69:8241-8. PubMed
  • Tanwar PS,Lee HJ,Zhang L,Zukerberg LR,Taketo MM,Rueda BR,Teixeira JM. Constitutive Activation of Beta-Catenin in Uterine Stroma and Smooth Muscle Leads to the Development of Mesenchymal Tumors in Mice. Biol Reprod 2009; 81:545-52. PubMed
  • Munro EG,Jain M,Oliva E,Kamal N,Lele SM,Lynch MP,Guo L,Fu K,Sharma P,Remmenga S,Growdon WB,Davis JS,Rueda BR,Batra SK. Upregulation of MUC4 in Cervical Squamous Cell Carcinoma: Pathologic Significance. Int J Gynecol Pathol 2009; 28:127-33. PubMed
  • Imamura T,Kikuchi H,Herraiz MT,Park DY,Mizukami Y,Mino-Kenduson M,Lynch MP,Rueda BR,Benita Y,Xavier RJ,Chung DC. HIF-1alpha and HIF-2alpha have divergent roles in colon cancer. Int J Cancer 2008; 124:763-71. PubMed
  • Rene Gonzalez R, Watters A, Xu Y, Singh UP, Mann DR, Rueda BR, Penichet ML. Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer. Breast Cancer Res 2009; 11:R36. PubMed
  • Carino C,Olawaiye AB,Cherfils S,Serikawa T,Lynch MP,Rueda BR,Gonzalez RR. Leptin regulation of proangiogenic molecules in benign and cancerous endometrial cells. Int J Cancer 2008; 123:2782-90. PubMed
  • Growdon WB,Boisvert SL,Akhavanfard S,Oliva E,Dias-Santagata DC,Kojiro S,Horowitz NS,Iafrate AJ,Borger DR,Rueda BR. Decreased survival in EGFR gene amplified vulvar carcinoma. Gynecol Oncol 2008; 111:289-97. PubMed
  • Olawaiye AB,Rauh-Hain JA,Withiam-Leitch M,Rueda B,Goodman A,del Carmen MG. Utility of pre-operative serum CA-125 in the management of uterine papillary serous carcinoma. Gynecol Oncol 2008; 110:293-8. PubMed
  • Tilly JL,Rueda BR. Minireview: stem cell contribution to ovarian development, function, and disease. Endocrinology 2008; 149:4307-11. PubMed
  • Henkes LE,Sullivan BT,Lynch MP,Kolesnick R,Arsenault D,Puder M,Davis JS,Rueda BR. Acid sphingomyelinase involvement in tumor necrosis factor alpha-regulated vascular and steroid disruption during luteolysis in vivo. Proc Natl Acad Sci U S A 2008; 105:7670-5. PubMed
  • Cherry JA, Hou X, Rueda BR, Davis JS, Townson DH. Microvascular Endothelial Cells of the Bovine Corpus Luteum: A Comparative Examination of the Estrous Cycle and Pregnancy. J Reprod Dev 2008; 54:183-91. PubMed
  • Styer AK, Sullivan BT, Puder M, Arsenault D, Petrozza JC, Serikawa T, Chang S, Hasan T, Gonzalez RR, Rueda BR. Ablation of leptin signaling disrupts the establishment, development, and maintenance of endometriosis-like lesions in a murine model. Endocrinology 2007; 149:506-14. PubMed
  • Sakamoto H, Friel AM, Wood AW, Guo L, Ilic A, Seiden MV, Chung DC, Lynch MP, Serikawa T, Munro E, Oliva E, Orsulic S, Kirley SD, Foster R, Zukerberg LR, Rueda BR. Mechanisms of Cables 1 gene inactivation in human ovarian cancer development. Cancer Biol Ther 2008; 7:180-88. PubMed
  • Hou X, Arvisais EW, Jiang C, Chen DB, Roy SK, Pate JL, Hansen TR, Rueda BR, Davis JS. Prostaglandin F2{alpha} Stimulates the Expression and Secretion of Transforming Growth Factor B1 Via Induction of the Early Growth Response 1 Gene (EGR1) in the Bovine Corpus Luteum. Mol Endocrinol 2007; 22:403-14. PubMed
  • Friel AM, Sergent PA, Patnaude C, Szotek PP, Oliva E, Scadden DT, Seiden MV, Foster R, Rueda BR. Functional analyses of the cancer stem cell-like properties of human endometrial tumor initiating cells. Cell Cycle 2008; 7:242-9. PubMed
  • Park do Y, Sakamoto H, Kirley SD, Ogino S, Kawasaki T, Kwon E, Mino-Kenudson M, Lauwers GY, Chung DC, Rueda BR, Zukerberg LR. The Cables gene on chromosome 18q is silenced by promoter hypermethylation and allelic loss in human colorectal cancer. Am J Pathol 2007; 171:1509-19. PubMed
  • Lee HJ, Sakamoto H, Luo H, Skaznik-Wikiel ME, Friel AM, Niikura T, Tilly JC, Niikura Y, Klein R, Styer AK, Zukerberg LR, Tilly JL, Rueda BR. Loss of CABLES1, a cyclin-dependent kinase-interacting protein that inhibits cell cycle progression, results in germline expansion at the expense of oocyte quality in adult female mice. Cell Cycle 2007; 6:2678-84. PubMed
  • Gonzalez RR, Cherfils S, Escobar M, Yoo JH, Carino C, Styer AK, Sullivan BT, Sakamoto H, Olawaiye A, Serikawa T, Lynch MP, Rueda BR. Leptin signaling promotes the growth of mammary tumors and increases the expression of vascular endothelial growth factor (VEGF) and its receptor type two (VEGF-R2). J Biol Chem 2006; 281:26320-8. PubMed
  • Mizukami Y, Jo WS, Duerr EM, Gala M, Li J, Zhang X, Zimmer MA, Iliopoulos O, Zukerberg LR, Kohgo Y, Lynch MP, Rueda BR, Chung DC. Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med 2005; 11:992-7. PubMed
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