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Conor  Lynch

Conor Lynch, PhD

Research Department Chair, Tumor Microenvironment and Metastasis
Research Program Lead, Cancer Biology & Evolution Program
Chair, Tumor Microenvironment and Metastasis

Program: Tumor Microenvironment and Metastasis

Research Program: Cancer Biology & Evolution Program


  • Overview


    • Tumor Microenvironment and Metastasis
    • Genitourinary Oncology
    • Pentecost Family Myeloma Research Center
    • Cancer Biology & Evolution Program
    • Molecular Oncology & Drug Discovery Program
    • Center of Excellence for Evolutionary Therapy

    Education & Training


    • Dublin City University, Ireland, PhD - Cancer Biology,Molecular Biology
  • Research Interest

    The goal of our laboratory is to understand how metastatic prostate cancer cells interact with the bone microenvironment to establish and grow as secondary cancers using in vivo and in vitro techniques. The lab has made major inroads into defining how matrix metalloproteinases (MMPs) contribute the prostate cancer progression in bone.

  • Publications

    • Bishop RT, Miller AK, Froid M, Nerlakanti N, Li T, Frieling JS, Nasr MM, Nyman KJ, Sudalagunta PR, Canevarolo RR, Silva AS, Shain KH, Lynch CC, Basanta D. The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease. Nat Commun. 2024 Mar.15(1):2458. Pubmedid: 38503736. Pmcid: PMC10951361.
    • Frieling JS, Tordesillas L, Bustos XE, Ramello MC, Bishop RT, Cianne JE, Snedal SA, Li T, Lo CH, de la Iglesia J, Roselli E, Benzaïd I, Wang X, Kim Y, Lynch CC, Abate-Daga D. γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer. Sci Adv. 2023 May.9(18):eadf0108. Pubmedid: 37134157. Pmcid: PMC10156127.
    • Nasr MM, Lynch CC. How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy. Cancer Metastasis Rev. 2023 Dec.42(4):1133-1146. Pubmedid: 37442876. Pmcid: PMC10713810.
    • Baratchart E, Lo CH, Lynch CC, Basanta D. Integrated computational and in vivo models reveal Key Insights into macrophage behavior during bone healing. PLoS Comput Biol. 2022 May.18(5):e1009839. Pubmedid: 35559958. Pmcid: PMC9106165.
    • Lo CH, Shay G, McGuire J, Li T, Shain K, Choi JY, Fuerst R, Roush WR, Knapinska AM, Fields GB, Lynch CC. Host-Derived Matrix Metalloproteinase-13 Activity Promotes Multiple Myeloma-Induced Osteolysis and Reduces Overall Survival. Cancer Res. 2021 May.81(9):2415-2428. Pubmedid: 33526510. Pmcid: PMC8809361.
    • Lo CH, Baratchart E, Basanta D, Lynch CC. Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair. Sci Rep. 2021 Mar.11(1):6055. Pubmedid: 33723343. Pmcid: PMC7961065.
    • Araujo A, Cook LM, Frieling JS, Tan W, Copland JA, Kohli M, Gupta S, Dhillon J, Pow-Sang J, Lynch CC, Basanta D. Quantification and Optimization of Standard-of-Care Therapy to Delay the Emergence of Resistant Bone Metastatic Prostate Cancer. Cancers (Basel). 2021 Feb.13(4). Pubmedid: 33567529. Pmcid: PMC7915310.
    • McGuire JJ, Frieling JS, Lo CH, Li T, Muhammad A, Lawrence HR, Lawrence NJ, Cook LM, Lynch CC. Mesenchymal stem cell-derived interleukin-28 drives the selection of apoptosis resistant bone metastatic prostate cancer. Nat Commun. 2021 Feb.12(1):723. Pubmedid: 33526787. Pmcid: PMC7851397.
    • Vaught DB, Merkel AR, Lynch CC, Edwards J, Tantawy MN, Hilliard T, Wang S, Peterson T, Johnson RW, Sterling JA, Brantley-Sieders D. EphA2 Is a Clinically Relevant Target for Breast Cancer Bone Metastatic Disease. JBMR Plus. 2021 Apr.5(4):e10465. Pubmedid: 33869989. Pmcid: PMC8046157.
    • Frieling JS, Li T, Tauro M, Lynch CC. Prostate cancer-derived MMP-3 controls intrinsic cell growth and extrinsic angiogenesis. Neoplasia. 2020 Oct.22(10):511-521. Pubmedid: 32896761. Pmcid: PMC7481881.
    • McGuire JJ, Nerlakanti N, Lo CH, Tauro M, Utset-Ward TJ, Reed DR, Lynch CC. Histone deacetylase inhibition prevents the growth of primary and metastatic osteosarcoma. Int J Cancer. 2020 Nov.147(10):2811-2823. Pubmedid: 32599665. Pmcid: PMC7787271.
    • Taylor-King JP, Buenzli PR, Chapman SJ, Lynch CC, Basanta D. Modeling Osteocyte Network Formation: Healthy and Cancerous Environments. Front Bioeng Biotechnol. 2020 Jul.8:757. Pubmedid: 32793566. Pmcid: PMC7387425.
    • Roselli E, Frieling JS, Thorner K, Ramello MC, Lynch CC, Abate-Daga D. CAR-T Engineering: Optimizing Signal Transduction and Effector Mechanisms. BioDrugs. 2019 Sep.33(6):647-659. Pubmedid: 31552606.
    • Cook LM, Frieling JS, Nerlakanti N, McGuire JJ, Stewart PA, Burger KL, Cleveland JL, Lynch CC. Betaglycan drives the mesenchymal stromal cell osteogenic program and prostate cancer-induced osteogenesis. Oncogene. 2019 Oct.38(44):6959-6969. Pubmedid: 31409900. Pmcid: PMC7771554.
    • Zhao N, Peacock SO, Lo CH, Heidman LM, Rice MA, Fahrenholtz CD, Greene AM, Magani F, Copello VA, Martinez MJ, Zhang Y, Daaka Y, Lynch CC, Burnstein KL. Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer. Sci Transl Med. 2019 Jun.11(498). Pubmedid: 31243151. Pmcid: PMC7864378.
    • Frieling JS, Lynch CC. Proteolytic Regulation of Parathyroid Hormone-Related Protein: Functional Implications for Skeletal Malignancy. Int J Mol Sci. 2019 Jun.20(11). Pubmedid: 31181800. Pmcid: PMC6600663.
    • Araujo A, Cook LM, Lynch CC, Basanta D. Size Matters: Metastatic Cluster Size and Stromal Recruitment in the Establishment of Successful Prostate Cancer to Bone Metastases. Bull Math Biol. 2018 May.80(5):1046-1058. Pubmedid: 29600344. Pmcid: PMC6482048.
    • Lo CH, Lynch CC. Multifaceted Roles for Macrophages in Prostate Cancer Skeletal Metastasis. Front Endocrinol (Lausanne). 2018 May.9:247. Pubmedid: 29867776. Pmcid: PMC5968094.
    • Warman PI, Kaznatcheev A, Araujo A, Lynch CC, Basanta D. Fractionated follow-up chemotherapy delays the onset of resistance in bone metastatic prostate cancer. Games (Basel). 2018 Jun.9(2). Pubmedid: 33552562. Pmcid: PMC7864372.
    • Tauro M, Lynch CC. Cutting to the Chase: How Matrix Metalloproteinase-2 Activity Controls Breast-Cancer-to-Bone Metastasis. Cancers (Basel). 2018 Jun.10(6). Pubmedid: 29874869. Pmcid: PMC6025260.
    • Betts BC, Locke FL, Sagatys EM, Pidala J, Walton K, Menges M, Reff J, Saha A, Djeu JY, Kiluk JV, Lee MC, Kim J, Kang CW, Tang CA, Frieling J, Lynch CC, List A, Rodriguez PC, Blazar BR, Conejo-Garcia JR, Del Valle JR, Hu CA, Anasetti C. Inhibition of Human Dendritic Cell ER Stress Response Reduces T Cell Alloreactivity Yet Spares Donor Anti-tumor Immunity. Front Immunol. 2018 Dec.9:2887. Pubmedid: 30574153. Pmcid: PMC6291501.
    • Tauro M, Shay G, Sansil SS, Laghezza A, Tortorella P, Neuger AM, Soliman H, Lynch CC. Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth. Mol Cancer Ther. 2017 Mar.16(3):494-505. Pubmedid: 28069877. Pmcid: PMC5337166.
    • McGuire J, Utset-Ward TJ, Reed DR, Lynch CC. Re-calculating! Navigating through the osteosarcoma treatment roadblock. Pharmacol Res. 2017 Mar.117:54-64. Pubmedid: 27940205.
    • Ember SW, Lambert QT, Berndt N, Gunawan S, Ayaz M, Tauro M, Zhu JY, Cranfill PJ, Greninger P, Lynch CC, Benes CH, Lawrence HR, Reuther GW, Lawrence NJ, Schonbrunn E. Potent Dual BET Bromodomain-Kinase Inhibitors as Value-Added Multitargeted Chemical Probes and Cancer Therapeutics. Mol Cancer Ther. 2017 Jun.16(6):1054-1067. Pubmedid: 28336808. Pmcid: PMC5457702.
    • Shay G, Tauro M, Loiodice F, Tortorella P, Sullivan DM, Hazlehurst LA, Lynch CC. Selective inhibition of matrix metalloproteinase-2 in the multiple myeloma-bone microenvironment. Oncotarget. 2017 Jun.8(26):41827-41840. Pubmedid: 28611279. Pmcid: PMC5522031.
    • Lwin ST, Fowler JA, Drake MT, Edwards JR, Lynch CC, Edwards CM. A loss of host-derived MMP-7 promotes myeloma growth and osteolytic bone disease in vivo. Mol Cancer. 2017 Feb.16(1):49. Pubmedid: 28241871. Pmcid: PMC5330156.
    • Frieling JS, Shay G, Izumi V, Aherne ST, Saul RG, Budzevich M, Koomen J, Lynch CC. Matrix metalloproteinase processing of PTHrP yields a selective regulator of osteogenesis, PTHrP1-17. Oncogene. 2017 Aug.36(31):4498-4507. Pubmedid: 28368420. Pmcid: PMC7771297.
    • Bankaitis K, Borriello L, Cox T, Lynch C, Zijlstra A, Fingleton B, Gužvić M, Anderson R, Neman J. Meeting report: Metastasis Research Society-Chinese Tumor Metastasis Society joint conference on metastasis. Clin Exp Metastas. 2017 Apr.34(3-4):203-213. Pubmedid: 28260197.
    • Shay G, Lynch CC, Fingleton B. Moving targets: Emerging roles for MMPs in cancer progression and metastasis. Matrix Biol. 2016 Mar.44-46:200-206. Pubmedid: 25652204. Pmcid: PMC4564058.
    • Cook LM, Araujo A, Pow-Sang JM, Budzevich MM, Basanta D, Lynch CC. Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer. Sci Rep. 2016 Jul.6:29384. Pubmedid: 27411810. Pmcid: PMC4944130.
    • Shay G, Hazlehurst L, Lynch CC. Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities. J Mol Med (Berl). 2016 Jan.94(1):21-35. Pubmedid: 26423531. Pmcid: PMC4707075.
    • Yu D, Kahen E, Cubitt CL, McGuire J, Kreahling J, Lee J, Altiok S, Lynch CC, Sullivan DM, Reed DR. Identification of Synergistic, Clinically Achievable, Combination Therapies for Osteosarcoma. Sci Rep. 2015 Nov.5:16991. Pubmedid: 26601688. Pmcid: PMC4658502.
    • Frieling JS, Basanta D, Lynch CC. Current and emerging therapies for bone metastatic castration-resistant prostate cancer. Cancer Control. 2015 Jan.22(1):109-120. Pubmedid: 25504285. Pmcid: PMC4673894.
    • Luhach I, Idiyatullin D, Lynch CC, Corum C, Martinez GV, Garwood M, Gillies RJ. Rapid ex vivo imaging of PAIII prostate to bone tumor with SWIFT-MRI. Magn Reson Med. 2014 Sep.72(3):858-863. Pubmedid: 24155275. Pmcid: PMC3997623.
    • Cook LM, Shay G, Aruajo A, Lynch CC. Integrating new discoveries into the "vicious cycle" paradigm of prostate to bone metastases. Cancer Metastasis Rev. 2014 Sep.33(2-3):511-525. Pubmedid: 24414228. Pmcid: PMC4096318.
    • Araujo A, Cook LM, Lynch CC, Basanta D. An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer. Cancer Res. 2014 May.74(9):2391-2401. Pubmedid: 24788098. Pmcid: PMC4023121.
    • Gallaher J, Cook LM, Gupta S, Araujo A, Dhillon J, Park JY, Scott JG, Pow-Sang J, Basanta D, Lynch CC. Improving treatment strategies for patients with metastatic castrate resistant prostate cancer through personalized computational modeling. Clin Exp Metastas. 2014 Dec.31(8):991-999. Pubmedid: 25173680. Pmcid: PMC5399888.
    • Cook LM, Shay G, Araujo A, Lynch CC. Erratum to: Integrating new discoveries into the "vicious cycle" paradigm of prostate to bone metastases. Cancer Metastasis Rev. 2014 Dec.33(4):1125. Pubmedid: 25096218.
    • Tauro M, McGuire J, Lynch CC. New approaches to selectively target cancer-associated matrix metalloproteinase activity. Cancer Metastasis Rev. 2014 Dec.33(4):1043-1057. Pubmedid: 25325988.
    • Shah M, Huang D, Blick T, Connor A, Reiter LA, Hardink JR, Lynch CC, Waltham M, Thompson EW. An MMP13-selective inhibitor delays primary tumor growth and the onset of tumor-associated osteolytic lesions in experimental models of breast cancer. PLoS One. 2012 May.7(1):e29615. Pubmedid: 22253746. Pmcid: PMC3256168.
    • Thiolloy S, Edwards JR, Fingleton B, Rifkin DB, Matrisian LM, Lynch CC. An osteoblast-derived proteinase controls tumor cell survival via TGF-beta activation in the bone microenvironment. PLoS One. 2012 May.7(1):e29862. Pubmedid: 22238668. Pmcid: PMC3251607.
    • Halpern JL, Kilbarger A, Lynch CC. Mesenchymal stem cells promote mammary cancer cell migration in vitro via the CXCR2 receptor. Cancer Lett. 2011 Sep.308(1):91-99. Pubmedid: 21601983. Pmcid: PMC3311035.
    • Nyman JS, Lynch CC, Perrien DS, Thiolloy S, O'Quinn EC, Patil CA, Bi X, Pharr GM, Mahadevan-Jansen A, Mundy GR. Differential effects between the loss of MMP-2 and MMP-9 on structural and tissue-level properties of bone. J Bone Miner Res. 2011 Jun.26(6):1252-1260. Pubmedid: 21611966. Pmcid: PMC3312757.
    • Lynch CC, Vargo-Gogola T, Matrisian LM, Fingleton B. Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA. J Oncol. 2011 Jul.2010:530745. Pubmedid: 20628524. Pmcid: PMC2902104.
    • Lynch CC. Matrix metalloproteinases as master regulators of the vicious cycle of bone metastasis. Bone. 2011 Jan.48(1):44-53. Pubmedid: 20601294.
    • Bi X, Patil CA, Lynch CC, Pharr GM, Mahadevan-Jansen A, Nyman JS. Raman and mechanical properties correlate at whole bone- and tissue-levels in a genetic mouse model. J Biomech. 2011 Jan.44(2):297-303. Pubmedid: 21035119. Pmcid: PMC3019269.
    • Fingleton B, Lynch CC. A new dress code for MMPs: cleavage optional. Dev Cell. 2010 Jan.18(1):3-4. Pubmedid: 20152171.
    • Fowler JA, Mundy GR, Lwin ST, Lynch CC, Edwards CM. A murine model of myeloma that allows genetic manipulation of the host microenvironment. Dis Model Mech. 2010 Feb.2(11-12):604-611. Pubmedid: 19779066. Pmcid: PMC2776114.
    • Schoenecker J, Mignemi N, Stutz C, Liu Q, Edwards J, Lynch C, Holt G, Schwartz H, Mencio G, Hamm H. 2010 Young Investigator Award winner: Therapeutic aprotinin stimulates osteoblast proliferation but inhibits differentiation and bone matrix mineralization. Spine (Phila Pa 1976). 2010 Apr.35(9):1008-1016. Pubmedid: 20407341.
    • Min Y, Ren X, Vaught DB, Chen J, Donnelly E, Lynch CC, Lin PC. Tie2 signaling regulates osteoclastogenesis and osteolytic bone invasion of breast cancer. Cancer Res. 2010 Apr.70(7):2819-2828. Pubmedid: 20233869. Pmcid: PMC2848896.
    • Bruni-Cardoso A, Johnson LC, Vessella RL, Peterson TE, Lynch CC. Osteoclast-derived matrix metalloproteinase-9 directly affects angiogenesis in the prostate tumor-bone microenvironment. Mol Cancer Res. 2010 Apr.8(4):459-470. Pubmedid: 20332212. Pmcid: PMC2946627.
    • Martin MD, Fingleton B, Lynch CC, Wells S, McIntyre JO, Piston DW, Matrisian LM. Establishment and quantitative imaging of a 3D lung organotypic model of mammary tumor outgrowth. Clin Exp Metastas. 2009 Jan.25(8):877-885. Pubmedid: 18787962. Pmcid: PMC2588650.
    • Thiolloy S, Halpern J, Holt GE, Schwartz HS, Mundy GR, Matrisian LM, Lynch CC. Osteoclast-derived matrix metalloproteinase-7, but not matrix metalloproteinase-9, contributes to tumor-induced osteolysis. Cancer Res. 2009 Aug.69(16):6747-6755. Pubmedid: 19679556. Pmcid: PMC2745595.
    • Welch DR, Cooper CR, Hurst DR, Lynch CC, Martin MD, Vaidya KS, VanSaun MN, Mastro AM. Metastasis Research Society-American Association For Cancer Research Joint Conference on Metastasis. Cancer Res. 2008 Dec.68(23):9578-9582. Pubmedid: 19047132. Pmcid: PMC2741417.
    • Holt GE, Halpern JL, Lynch CC, Devin CJ, Schwartz HS. Imaging analysis of the in vivo bioreactor: a preliminary study. Clin Orthop Relat Res. 2008 Aug.466(8):1890-1896. Pubmedid: 18506563. Pmcid: PMC2584254.
    • Martin MD, Carter KJ, Jean-Philippe SR, Chang M, Mobashery S, Thiolloy S, Lynch CC, Matrisian LM, Fingleton B. Effect of ablation or inhibition of stromal matrix metalloproteinase-9 on lung metastasis in a breast cancer model is dependent on genetic background. Cancer Res. 2008 Aug.68(15):6251-6259. Pubmedid: 18676849. Pmcid: PMC2789265.
    • Halpern J, Lynch CC, Fleming J, Hamming D, Martin MD, Schwartz HS, Matrisian LM, Holt GE. The application of a murine bone bioreactor as a model of tumor: bone interaction. Clin Exp Metastas. 2007 Mar.23(7-8):345-356. Pubmedid: 17136574.
    • Lynch CC, Vargo-Gogola T, Martin MD, Fingleton B, Crawford HC, Matrisian LM. Matrix metalloproteinase 7 mediates mammary epithelial cell tumorigenesis through the ErbB4 receptor. Cancer Res. 2007 Jul.67(14):6760-6767. Pubmedid: 17638887.
    • Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK, Vargo-Gogola TC, Begtrup JL, Peterson TE, Fingleton B, Shirai T, Matrisian LM, Futakuchi M. MMP-7 promotes prostate cancer-induced osteolysis via the solubilization of RANKL. Cancer Cell. 2005 May.7(5):485-496. Pubmedid: 15894268.
    • Lynch CC, Crawford HC, Matrisian LM, McDonnell S. Epidermal growth factor upregulates matrix metalloproteinase-7 expression through activation of PEA3 transcription factors. Int J Oncol. 2004 Jun.24(6):1565-1572. Pubmedid: 15138601.
    • McIntyre JO, Fingleton B, Wells KS, Piston DW, Lynch CC, Gautam S, Matrisian LM. Development of a novel fluorogenic proteolytic beacon for in vivo detection and imaging of tumour-associated matrix metalloproteinase-7 activity. Biochem J. 2004 Feb.377(Pt 3):617-628. Pubmedid: 14556651. Pmcid: PMC1223892.
    • Harmey JH, Bucana CD, Lu W, Byrne AM, McDonnell S, Lynch C, Bouchier-Hayes D, Dong Z. Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion. Int J Cancer. 2002 Oct.101(5):415-422. Pubmedid: 12216068.
    • Lynch CC, Matrisian LM. Matrix metalloproteinases in tumor-host cell communication. Differentiation. 2002 Dec.70(9-10):561-573. Pubmedid: 12492497.
    • Lynch CC, McDonnell S. The role of matrilysin (MMP-7) in leukaemia cell invasion. Clin Exp Metastas. 2000 Dec.18(5):401-406. Pubmedid: 11467772.
    • McDonnell S, Morgan M, Lynch C. Role of matrix metalloproteinases in normal and disease processes. Biochem Soc Trans. 1999 Aug.27(4):734-740. Pubmedid: 10917674.
  • Grants

    • Title: Developing ULK3 inhibitors for Multiple Myeloma
      Sponsor: Moffitt Cancer Center
      PI (Contact): Lynch, C., PI: Lawrence, N.
    • Title: Proprietary arginine vasopressin receptor type 1a (AVPR1a) antagonists for treatment of lethal prostate cancer
      Sponsor: US Army
      PI: Lynch, C.
    • Title: Identifying How HDAC Suppression of SLC17A7 Drives Osteosarcoma Progression and Metastasis
      Sponsor: Florida Biomedical Research Program (FBRP)
      PI: Lynch, C.
    • Title: Role of ULK3 in Sensitive and Refractory Multiple Myeloma
      Sponsor: Nat Institutes of Health
      PI: Lynch, C.
    • Title: Local and Systemic Control of Multiple Myeloma Colonization and Growth by MMP-13
      Sponsor: Nat Institutes of Health
      PI: Lynch, C.
    • Title: Defining bone ecosystem effects on metastatic prostate cancer evolution and treatment response using an integrated mathematical modeling approach
      Sponsor: Nat Institutes of Health
      PI (Contact): Lynch, C., PI (MPI): Basanta Gutierrez, D.

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