Photo of James W. Mier,  MD

James W. Mier, MD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 667-0430
Fax: (617) 975-5398


jmier@caregroup.Harvard.edu

James W. Mier, MD

Beth Israel Deaconess Medical Center

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our laboratory is interested in the signaling pathways downstream of ras that are involved in the regulation of expression of actin-binding proteins such as tropomyosin (TM) that have been shown to affect the growth and metastatic potential of tumor cells. We have shown that the expression of TM-2 is suppressed by oncogenic ras through a pathway that involves Raf, but not MEK. To further clarify the specific pathway involved, we are assessing the effects of various dominant negative fibroblasts and epithelial cells. Our laboratory is also interested in the factors that regulate the expression of the leukocyte adhesion molecule L-selection. Unlike most adhesion molecules, L-selectin is shed from the cell surface in response to leukocyte activation or exposure to L-selectin ligands. Ligand-induced shedding appears to be mediated by a protease distinct from the recently characterized ADAMS family member TACE (TNF-Alpha Converting Enzyme), which is responsible for the shedding of L-selectin in response to leukocyte activation. We are currently investigating the signaling pathways activated by encountering L-selectin ligands.

Publications

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  • Sullivan RJ, Ibrahim N, Lawrence DP, Aldridge J, Giobbie-Hurder A, Hodi FS, Flaherty KT, Conley C, Mier JW, Atkins MB, McDermott DF. A Phase I Trial of Bortezomib and Sorafenib in Advanced Malignant Melanoma. Oncologist 2015; 20:617-8. PubMed
  • Zhang L, Wang X, Bullock AJ, Callea M, Shah H, Song J, Moreno K, Visentin B, Deutschman D, Alsop DC, Atkins MB, Mier JW, Signoretti S, Bhasin M, Sabbadini RA, Bhatt RS. Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer. Clin Cancer Res 2015. PubMed
  • Mier JW. Immune checkpoint inhibitors in the treatment of metastatic melanoma. Clin Ther 2015. PubMed
  • McDermott DF, Cheng SC, Signoretti S, Margolin KA, Clark JI, Sosman JA, Dutcher JP, Logan TF, Curti BD, Ernstoff MS, Appleman L, Wong MK, Khushalani NI, Oleksowicz L, Vaishampayan UN, Mier JW, Panka DJ, Bhatt RS, Bailey AS, Leibovich BC, Kwon ED, Kabbinavar FF, Belldegrun AS, Figlin RA, Pantuck AJ, Regan MM, Atkins MB. The high-dose aldesleukin "select" trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res 2015; 21:561-8. PubMed
  • Panka DJ, Buchbinder E, Giobbie-Hurder A, Schalck AP, Montaser-Kouhsari L, Sepehr A, Lawrence DP, McDermott DF, Cohen R, Carlson A, Wargo JA, Merritt R, Seery VJ, Hodi FS, Gunturi A, Fredrick D, Atkins MB, Iafrate AJ, Flaherty KT, Mier JW, Sullivan RJ. Clinical utility of a blood-based BRAF(V600E) mutation assay in melanoma. Mol Cancer Ther 2014. PubMed
  • Wang X, Bullock AJ, Zhang L, Wei L, Yu D, Mahagaokar K, Alsop DC, Mier JW, Atkins MB, Coxon A, Oliner J, Bhatt RS. The role of angiopoietins as potential therapeutic targets in renal cell carcinoma. Transl Oncol 2014. PubMed
  • Panka DJ, Mier JW, Sullivan RJ. Assaying for BRAF V600E in tissue and blood in melanoma. Methods Mol Biol 2013; 1102:117-36. PubMed
  • Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS ONE 2014; 9:e101286. PubMed
  • Zhu S, Cohen MB, Bjorge JD, Mier JW, Cho DC. PI3K inhibition potentiates Bcl-2-dependent apoptosis in renal carcinoma cells. J Cell Mol Med 2013; 17:377-85. PubMed
  • Wang X, Zhang L, O'Neill A, Bahamon B, Alsop DC, Mier JW, Goldberg SN, Signoretti S, Atkins MB, Wood CG, Bhatt RS. Cox-2 inhibition enhances the activity of sunitinib in human renal cell carcinoma xenografts. Br J Cancer 2013; 108:319-26. PubMed
  • Cho DC, Mier JW. Dual inhibition of PI3-kinase and mTOR in renal cell carcinoma. Curr Cancer Drug Targets 2013; 13:126-42. PubMed
  • Panka DJ, Liu Q, Geissler AK, Mier JW. Effects of HDM2 antagonism on sunitinib resistance, p53 activation, SDF-1 induction, and tumor infiltration by CD11b+/Gr-1+ myeloid derived suppressor cells. Mol Cancer 2013; 12:17. PubMed
  • Hong DS, Kurzrock R, Supko JG, He X, Naing A, Wheler J, Lawrence D, Eder JP, Meyer CJ, Ferguson DA, Mier J, Konopleva M, Konoplev S, Andreeff M, Kufe D, Lazarus H, Shapiro GI, Dezube BJ. A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas. Clin Cancer Res 2012; 18:3396-406. PubMed
  • Pandya SS, Mier JW, McDermott DF, Cho DC. Addition of gemcitabine at the time of sunitinib resistance in metastatic renal cell cancer. BJU Int 2011. PubMed
  • Panka DJ, Sullivan RJ, Mier JW. An inexpensive, specific and highly sensitive protocol to detect the BrafV600E mutation in melanoma tumor biopsies and blood. Melanoma Res 2010; 20:401-7. PubMed
  • Bhatt RS, Wang X, Zhang L, Collins MP, Signoretti S, Alsop DC, Goldberg SN, Atkins MB, Mier JW. Renal cancer resistance to antiangiogenic therapy is delayed by restoration of angiostatic signaling. Mol Cancer Ther 2010; 9:2793-802. PubMed
  • Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S, Mier JW. The Efficacy of the Novel Dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 Compared with Rapamycin in Renal Cell Carcinoma. Clin Cancer Res 2010; 16:3628-38. PubMed
  • Atkins MB, Bukowski RM, Escudier BJ, Figlin RA, Hudes GH, Kaelin WG, Linehan WM, McDermott DF, Mier JW, Pedrosa I, Rini BI, Signoretti S, Sosman JA, Teh BT, Wood CG, Zurita AJ, King L. Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference. Cancer 2009; 115:2247-51. PubMed
  • Cho DC,Puzanov I,Regan MM,Schwarzberg T,Seery V,Lee MY,Liu V,Bhatt R,Koon H,Mier JW,Sosman JA,Atkins MB,McDermott DF. Retrospective analysis of the safety and efficacy of interleukin-2 after prior VEGF-targeted therapy in patients with advanced renal cell carcinoma. J Immunother 2009; 32:181-5. PubMed
  • Sosman JA, Carrillo C, Urba WJ, Flaherty L, Atkins MB, Clark JI, Dutcher J, Margolin KA, Mier J, Gollob J, Kirkwood JM, Panka DJ, Crosby NA, O'Boyle K, LaFleur B, Ernstoff MS. Three phase II cytokine working group trials of gp100 (210M) peptide plus high-dose interleukin-2 in patients with HLA-A2-positive advanced melanoma. J Clin Oncol 2008; 26:2292-8. PubMed
  • Negin B, Panka D, Wang W, Siddiqui M, Tawa N, Mullen J, Tahan S, Mandato L, Polivy A, Mier J, Atkins M. Effect of melanoma on immune function in the regional lymph node basin. Clin Cancer Res 2008; 14:654-9. PubMed
  • Panka DJ, Cho DC, Atkins MB, Mier JW. GSK-3beta inhibition enhances sorafenib-induced apoptosis in melanoma cell lines. J Biol Chem 2007; 283:726-32. PubMed
  • Cho D, Signoretti S, Regan M, Mier JW, Atkins MB. The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res 2007; 13:758s-763s. PubMed
  • Cho D, Atkins MB, Mier JW. Inhibition of glycogen synthase 3b (GSK3b) enhances the in vitro activity of the Akt inhibitor perifosine in renal cell carcinoma (RCC) cell lines J Am Diet Assoc 2006.
  • Cho D, Panka P, Panka D, Atkins MB, Mier JW. Sensitivity of renal cell carcinoma (RCC) cell lines to Sorafenib in vitro is dependent upon Akt and GSK3activity J Am Diet Assoc 2006; 2006:4515.
  • Robertson MJ, Mier JW, Logan T, Atkins M, Koon H, Koch KM, Kathman S, Pandite LN, Oei C, Kirby LC, Jewell RC, Bell WN, Thurmond LM, Weisenbach J, Roberts S, Dar MM. Clinical and biological effects of recombinant human interleukin-18 administered by intravenous infusion to patients with advanced cancer. Clin Cancer Res 2006; 12:4265-73. PubMed
  • Panka DJ, Atkins MB, Mier JW. Targeting the mitogen-activated protein kinase pathway in the treatment of malignant melanoma. Clin Cancer Res 2006; 12:2371s-2375s. PubMed
  • Atkins MB, Elder DE, Essner R, Flaherty KT, Gajewski TF, Haluska FG, Hwu P, Keilholz U, Kirkwood JM, Mier JW, Ross MI, Slingluff CL, Sondak VK, Sosman JA, Weinstock MA, King L. Innovations and challenges in melanoma: summary statement from the first Cambridge conference. Clin Cancer Res 2006; 12:2291s-2296s. PubMed
  • Panka DJ, Wang W, Atkins MB, Mier JW. The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells. Cancer Res 2006; 66:1611-9. PubMed
  • van der Mijn JC, Mier JW, Broxterman HJ, Verheul HM. Predictive biomarkers in renal cell cancer: insights in drug resistance mechanisms. Drug Resist Updat 2014; 17:77-88. PubMed
  • Bhatt R, Wang X, Zhang L, Bhasin M, Libermann T, O’Neil A, Signoretti S, Atkins M, Mier J, Goldberg SN. Cox-2 inhibition delays resistance to sunitinib in RCC xenograft models. 2009.
  • Panka DJ, Collins M, Atkins MB, Signoretti S, Mier JW. Enhancement of efficacy of sorafenib and sunitinib with the HDM2 antagonist MI-319 in RCC tumor xenografts. 2010.
  • Bhatt RS, Zhang L, Bullock A, Moreno K, Signoretti S, Atkins M, Sabbadini R, Mier J. Sphingosine-1-phosphate (S1P) as a novel target in renal cancer (RCC). 2010.
  • Bullock AJ, Zhang L, AM O’Neill, Percy A, Sukhatme V, Mier JW, Atkins MB, Bhatt RS. Plasma angiopoietin-2 (ANG2) as an angiogenic biomarker in renal cell carcinoma (RCC) 2010.
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