H. Michael Shepard, PhD
Cancer Research in the 21st Century

H. Michael Shepard, PhD Cancer Research in the 21st CenturyH. Michael Shepard, PhD Cancer Research in the 21st CenturyH. Michael Shepard, PhD Cancer Research in the 21st Century
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H. Michael Shepard, PhD
Cancer Research in the 21st Century

H. Michael Shepard, PhD Cancer Research in the 21st CenturyH. Michael Shepard, PhD Cancer Research in the 21st CenturyH. Michael Shepard, PhD Cancer Research in the 21st Century
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H. Michael Shepard

PUBLICATIONS (Favorites are in BOLD type)

  1.  Chen et al. Targeting deoxycytidine kinase improves symptoms in mouse models of multiple sclerosis. Immunology 168: 152-169, 2023.
  2. Wang L, et al. Targeting adenosine with adenosine deaminase to inhibit growth of solid tumors. Cancer Res. 81: 3319-3332, 2021. Describes method for reversing the immunosuppressive tumor microenvironment.
  3. Zhao C, et al. The growth of a xenograft breast cancer model with engineered hyaluronan-accumulating stroma is dependent on hyaluronan and independent of CD44. Oncotarget 10: 6561-6576, 2019.
  4. Shepard, HM. The Team that Just Wouldn’t Quit and a New Paradigm in Cancer Drug Discovery. Cell 179: 27-32. Story about the Team at Genentech that created trastuzumab.
  5. He Y, et al. Multiple cancer-specific antigens are targeted by a chimeric antigen receptor on a single cancer cell. JCI Insight. 2019 Dec 5;4(23):e135306. doi: 10.1172/jci.insight.135306. CAR-T cells that recognize multiple tumor associated antigens, thus preventing tumor cell escape.
  6. Li X, et al. Parallel Accumulation of Tumor Hyaluronan, Collagen, and Other Drivers of Tumor Progression. Clin Cancer Res. 2018 Oct 1;24(19):4798-4807. doi: 10.1158/1078-0432
  7. Marella M. et al. KIAA1199 expression and hyaluronan degradation colocalize in multiple sclerosis lesions. Glycobiology. 2018 Dec 1;28(12):958-967
  8. JR Infante, et al. Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with advanced solid tumors. Br. J. Cancer (2017), 1-9 (Published on-line).
  9. Shepard et al. Developments in therapy with monoclonal antibodies and related proteins. Clin Med (Lond). 2017 Jun;17(3):220-232
  10. Marella M et al. PH20 is not expressed in murine CNS and oligodendrocyte precursor cells. Ann Clin Transl Neurol. 2017 Feb 23;4(3):191-211.
  11. Hingorani, et al. Phase 1b study of PEGylated Recombinant Human Hyaluronidase and Gemcitabine in Patients with Advanced Pancreatic Cancer. Clin. Cancer Res. 2016 Jan 26, 2015 (Published on line).
  12. Shepard, HM. Breaching the Castle Walls: Hyaluronan Depletion as a Therapeutic Approach to Cancer Therapy. Front Oncol. 5: 192, 2015.
  13. C.J. Whatcott, C.H. Diep, P. Jiang, A. Watanabe, J. LoBello, C. Sima, G. Hostetter, H.M. Shepard, D.D. Von Hoff, H. Dan. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. Clin Cancer Res. 2015 Feb 18 [Epub ahead of print].
  14. N. C. Singha, T. Nekoroski, C. Zhao, R. Symons, P. Jiang, G.I. Frost, Z. Huang, H. M. Shepard. Tumor –Associated Hyaluronan Limits Efficacy of Monoclonal Antibody Therapy. Molecular Cancer Therapeutics 14(2): 523-532, 2015. Removal of hyaluronan from the tumor microenvironment allows access of MAbs for therapy of solid tumors.
  15. K.E. DelGiorno, M.A. Carlson, R. Osgood, P.P. Provenzano, J.S. Brockenbough, C.B. Thompson, H.M. Shepard, G.I. Frost, J.D. Potter, S.R. Hingorani. Response to Chauhan et al: Interstitial pressure and vascular collapse in pancreas cancer-fluids and solids, measurement and meaning. Cancer Cell 26(1):16-7, Jul 2014.
  16. Z. Huang, C. Zhao, Y. Chen, J.A. Cowell, G. Wei, A. Kultti, L. Huang, C.B. Thompson, S. Rosengren, G.I. Frost, H. M. Shepard. Recombinant Human Hyaluronidase PH20 Does Not Stimulate an Acute Inflammatory Response and Inhibits Lipopolysaccharide-Induced Neutrophil Recruitment in the Air Pouch Model of Inflammation. J Immunol published online 28 April 2014.
  17. A. Kultti, C. Zhao, N. C. Singha, S. Zimmerman, R. J. Osgood, R. Symons, P. Jiang, X. Li, C. B. Thompson, J. R. Infante, M. A. Jacobetz, D. A. Tuveson, G. I. Frost, H. M. Shepard, and Z. Huang. Accumulation of Extracellular Hyaluronan by Hyaluronan Synthase 3 Promotes Tumor Growth and Modulates the Pancreatic Cancer Microenvironment. BioMed Research International. Volume 2014, Article ID 817613, 15 pages, 2014.
  18. L. Jadin, L. Huang, G. Wei, Q. Zhao, A. Gelb, G. Frost, P. Jiang, H. M. Shepard. Characterization of a Novel Recombinant Hyaluronan Binding Protein for Tissue Hyaluronan Detection. Journal of Histochemistry & Cytochemistry, 12 pages, May 2014 (online publication).
  19. Z. Huang, C. Zhao, Y. Chen, J. A. Cowell, G. Wei, A. Kultti, L. Huang, C. B. Thompson, S. Rosengren, G. I. Frost, and H. M. Shepard. Recombinant Human Hyaluronidase PH20 (rHuPH20) Does Not Stimulate an Acute Inflammatory Response, and Inhibits LPS-Induced Neutrophil Recruitment in the Air Pouch Model of Inflammation. J. Immunol. 192: 5285–5295, 2014.
  20. A. Kultti, X. Li, P. Jiang, C. B. Thompson, G. Frost, H. M. Shepard. Therapeutic Targeting of Hyaluronan in the Tumor Stroma. Cancers 4(3), 873-903, 2012.
  21. M.A. Jocobetz, D.S. Chan, A. Neesse, T.E. Bapiro, N. Cook, K.K. Frese, C. Feig, T. Nakagawa, M.E. Caldwell, H.I. Zecchini, M.P. Olekma, P. Jiang, A. Kultti, C.B. Thompson, D.C. Maneval, D. Jodrell, G.I. Frost, H.M. Shepard, J.N. Skepper, D.A. Tuveson. Hyaluronan impairs Vascular Function and Drug Delivery in a Mouse Model of Pancreatic Cancer. GUT, 2012.
  22. P. Jiang, X. Li, C. Thompson, Z. Huang, Fl. Araiza, R. Osgood, G. Wei, M. Feldmann, G. Frost, H.M. Shepard. Effective Targeting of the Tumor Microenvironment for Cancer Therapy. Anticancer Res. 32: 1203-1212, 2012.
  23. L. L. Gompels, N. Malik, L. Madden, P. Jin, M. Feldmann, H. M. Shepard, E. M. Paleolog. Human Epidermal Growth Factor Receptor Bispecific Ligand Trap RB200: Abrogation Of Collagen Induced Arthritis In Combination With TNF Blockade. J Arthritis Research & Therapy, 2011. First proof of concept that growth factors activating the EGFR Family have a role in driving rheumatoid arthritis.
  24. C. B. Thompson, H. M. Shepard, P. M. O’Connor, S. Kadhim, P. Jiang, R.J. Osgood, X. Li, B.J. Sugarman, R. J. Connor, S. Nadjsombati, G. I. Frost. Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models. Mol Cancer Ther. (11): 3052-64, 2010.
  25. P. Jin, J. Zhang, M. Beryt, L. Turin, C. Brdlik, Y. Feng, X. Bai, J. Liu, B. Jorgenson, H. M. Shepard. Rational Optimization of a Bispecific Ligand Trap Targeting EGF Receptor Family Ligands. Mol. Med. 15:11-20, 2009. First description of an affinity-matured EGFR Family growth factor trap.
  26. H. M. Shepard, C.M. Brdlik, H. Schreiber. Signal integration: A framework for understanding the efficacy of therapeutics targeting the human EGFR family. J Clin Invest. (11): 3574-81, 2008.
  27. D. C. Maneval, P. Jin, H. M. Shepard. Pan-HER Biologics (Hermodulins) for the Treatment of Cancer. Drug Dev.Res. 69:472-479, 2008.
  28. Z. Huang, C. Brdlik, P. Jin, H. M. Shepard. A Pan-HER approach for cancer therapy: background, current status and future development. Exp.Opin.Biol.Ther. 9:97-110, 2008.
  29. H. M. Shepard, C.M. Brdlik, H. Schreiber. Signal integration: a framework for understanding efficacy of therapeutics targeting the human EGFR family. J.Clin.Invest. 118:3574-3581, 2008.
  30. J. Sarup, P. Jin, L. Turin, X. Bai, M. Beryt, C. Brdlik, J.N. Higaki, B. Jorgensen, F.W. Lau, P. Lindley, J. Lui, I. Ni, J. Rozzelle, R. Kumari, S.A. Watson, J. Zhang, H. M. Shepard. Human EGF receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activity in vitro and in human tumor xenografts. Mol.Cancer Ther. 7:3223-3236, 2008.
  31. P.F. Sumariwalla, P. Jin, D. Crawford, E. M. Paleolog, H. M. Shepard, M. Feldmann. Antagonism of the human epidermal growth factor receptor family controls disease severity in murine collagen- induced arthritis. Arthritis Rheum. 58(10): 3071-3080, 2008.
  32. P. Jin, J. Zhang, P. Sumariwalla, I., B. Jorgensen, D. Crawford, S. Phillips, M. Feldmann, H.M. Shepard, E.M. Paleolog. Novel splice variants derived from the receptor tyrosine kinase superfamily are potential therapeutics for rheumatoid arthritis. Arthritis Res.Ther. 10:R73, 2008.
  33. H. M. Shepard. Judo Biology. Voices of Breast Cancer: The Healing Companion: Stories for Courage, Comfort and Strength, (LaChance, New York, 2007).
  34. H.M. Shepard, Pei Jin, Zhu Pirot, Daniel C. Maneval. Herceptin. Handb Exp Pharmacol. 181-183-219, 2007.
  35. L.H. Bookbinder, A. Hofer, M.F. Haller, M.L. Zepeda, G.A. Keller, J.E. Lim, T.S. Edgington, H.M. Shepard, J.S. Patton, G.I. Frost. A Recombinant Human Enzyme for Enhanced Interstitial Transport of Therapeutics. J.Control.Release 114(2):230-241, 2006.
  36. S.T. Neuteboom, P.L. Karjian, C.R. Boyer, M. Berty, M. Pegram, G.M. Wahl, H.M. Shepard. Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction. Mol.Cancer Ther. 1(6):377-384, 2002.
  37. Q. Li, J. Lee, R. Castillo, M.S. Hixon, C. Pujol, V.R. Doppalapudi, H.M. Shepard, G.M. Wahl, T.J. Lobl, M.F. Chan. NB2001, a novel antibacterial agent with broad-spectrum activity and enhanced potency against -lactamase-producing strains. Antimicrob.Agents Chemother. 46(5):1262-1268, 2002.
  38. Q. Li, C. Boyer, J.Y. Lee, H.M. Shepard. A novel approach to thymidylate synthase as a target for cancer chemotherapy. Mol.Pharmacol. 59(3):446-452, 2001. Proof of concept that enzymes overexpressed in tumor suppressor deficient tumor cells can be used to activate prodrugs, thus establishing another technology for selective targeting of cancer vs.normal cells.
  39. D.B. Lackey, M.P. Groziak, M. Sergeeva, M. Beryt, C. Boyer, R.M. Stroud, P. Sayre, J.W. Park, P. Johnston, D. Slamon, H.M. Shepard, M. Pegram. Enzyme-catalyzed therapeutic agent (ECTA) design: activation of the antitumor ECTA compound NB1011 by thymidylate synthase. Biochem.Pharmacol. 61(2):179-189, 2001.
  40. S.C. Anderson, D.E. Johnson, M.P. Harris, H. Engler, W. Hancock, W.M. Huang, K.N. Wills, R.K/ Gregory, S. Sutjipto, S.F. Wen, S. Lofgren, H.M. Shepard, D.C. Maneval. p53 gene therapy in a rat model of hepatocellular carcinoma: intra-arterial delivery of a recombinant adenovirus. Clin.Cancer Res. 4(7):1649-1659, 1998. Demonstrates that adenovirus-mediated gene therapy can be useful for solid tumors. Later applied to Bladder Cancer.
  41. T. Watanabe, L. Kelsey, A. Ageitos, C. Kuszynski, K. Ino, D.G. Heimann, M.T. Varney, H.M. Shepard, M.T. Vaillancourt, D.C. Maneval, J.E. Talmadge. Enhancement of adenovirus-mediated gene transfer to human bone marrow cells. Leuk.Lymphoma 29(5-6):439- 451, 1998.
  42. S. P. Linke, M.P. Harris, S.E. Neugebauer, K.C. Clarkin, H.M. Shepard, D.C. Maneval, G. Wahl. P53-mediated accumulation of hypophosphorylated pRb after the G1 restriction point fails to halt cell cycle progression. Oncogene 15(3):337-345, 1997.
  43. H. Kock, M.P. Harris, S.C. Anderson, T. Machemer, W. Hancock, S. Sutjipto, K.N. Wills, R.J. Gregory, H.M. Shepard, M. Westphal, D.C. Maneval. Adenovirus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo. Int.J.Cancer 67(6):808-815, 1996.
  44. T. Watanabe, C. Kuszynski, K. Ino, D. G. Heimann, H.M. Shepard, Y. Yasui, D.C. Maneval, J.E. Talmadge. Gene transfer into human bone marrow hematopoietic cells mediated by adenovirus vectors. Blood 87(12):5032-5039, 1996.
  45. C.E. Kotts, F.M. Su, C. Leddy, T. Dodd, S. Scates, M.R. Shalaby, C.M. Wirth, D. Giltinan, R.W. Schroff, A.R. Fritzberg, H.M. Shepard, D.J. Slamon, B.M. Hutchins. 186Re-labeled antibodies to p185HER2 as HER2-targeted radioimmunopharmaceutical agents: comparison of physical and biological characteristics with 125I and 131I-labeled counterparts. Cancer Biother.Radiopharm. 11(2):133-144, 1996.
  46. M.P. Harris, S.Sutjipto, K.N. Wills, W. Hancock, D. Cornell, D.E. Johnson, R.J. Gregory, H.M. Shepard, D.C. Maneval. Adenovirus-mediated p53 gene transfer inhibits growth of human tumor cells expressing mutant p53 protein. Cancer Gene Ther. 3(2):121-130, 1996.
  47. B.G. Huyghe, X. Liu, S. Sutjipto, B.J. Sugarman, M.T. Horn, H.M. Shepard, C.J. Scandella, P. Shabram. Purification of a type 5 recombinant adenovirus encoding human p53 by column chromatography. Hum.Gene Ther. 6(11):1403-1416, 1995.
  48. L.C. Pagliaro, D. Antelman, D.E. Johnson, T. Machemer, E.A. McCulloch, E.J. Freireich, S.A. Stass, H.M. Shepard, D. Maneval, J.U. Gutterman. Recombinant human retinoblastoma protein inhibits cancer cell growth. Cell Growth Differ. 6(6):673-680, 1995.
  49. D. Antelman, T. Machemer, B. G. Huyghe, H.M. Shepard, D. Maneval, D.E. Johnson. Inhibition of tumor cell proliferation in vitro and in vivo by exogenous p110RB, the retinoblastoma tumor suppressor protein. Oncogene 10(4):697-704, 1995.
  50. S.F. Wen, M. Nodelman, K. Nared-Hood, J. Duncan, J. Geradts, H.M. Shepard. Retinoblastoma protein monoclonal antibodies with novel characteristics. J.Immunol.Methods 169(2):231-240, 1994.
  51. J.A. Kern, L. Torney, D. Weiner, A. Gazdar, H.M. Shepard, B. Fendly. Inhibition of human lung cancer cell line growth by an anti-p185HER2 antibody. Am.J.Respir.Cell Mol.Biol. 9(4):448-454, 1993.
  52. G.D. Lewis, I. Figari, B. Fendly, W.L. Wong, P. Carter, C. Gorman, and H.M. Shepard. Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol.Immunother. 37(4):255-263, 1993. Great review of our preclinical work including much new data characterizing anti-HER2 antibodies and the basis for the biomarker.
  53. S. Soomro, P. Taylor, H.M. Shepard, M. Feldmann, H.D. Sinnett, S. Shousha. c-ErbB-2 oncoprotein in screen-detected breast carcinoma: an immunohistological study. Int.J.Cancer 55(1):63-65, 1993.
  54. W. Hamel, M. Westphal, H.M. Shepard. Loss in expression of the retinoblastoma gene product in human gliomas is associated with advanced disease. J.Neurooncol. 16(2):159-165, 1993.
  55. C.C. Benz, G.K. Scott, J.C. Sarup, R.M. Johnson, D. Tripathy, E. Coronado, H.M. Shepard, C.K. Osborne. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res.Treat. 24(2):85-95, 1993.
  56. W.E. Holmes, M.X. Sliwkowski, R.W. Akita, W.J. Henzel, J. Lee, J.W. Park, D. Yansura, N.Abadi, H. Raab, G.D. Lewis, H.M. Shepard, Wun-Jing Kuang, W.I. Wood, D.V. Goeddel, R.L. Vandlen. Identification of Heregulin, a Specific Activator of p185erB2. Science 256: 1205-1210, 1992. Much cited paper re. the characterization of heregulins/neuregulins.
  57. H. Arnaout, P.M. Dawson, S. Soomro, P. Taylor, N.A. Theodorou, M. Feldmann, B.M. Fendly, H.M. Shepard, S. Shousha. HER2 (c-ErbB-2) oncoprotein expression in colorectal adenocarcinoma: an immunohistological study using three different antibodies. J.Clin.Pathol. 45(8):726-727, 1992
  58. P. Carter, L. Presta, C.M. Gorman, J.B. Ridgway, D. Henner, W.L. Wong, A.M. Rowland, C. Kotts, M.E. Carver, and H.M. Shepard. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc.Natl.Acad.Sci.U.S.A 89(10):4285-4289, 1992. Very important paper.
  59. J.W. Park, R. Stagg, G.D. Lewis, P. Carter, D. Maneval, D.J. Slamon, H. Jaffe, H.M. Shepard. Anti-p185HER2monoclonal antibodies: biological properties and potential for immunotherapy. Cancer Treat.Res. 61:193-211, 1992.
  60. M.R. Shalaby, H.M. Shepard, L. Presta, M.L. Rodrigues, P.C. Beverley, M. Feldmann, P. Carter. Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells overexpressing the HER2 protooncogene. J.Exp.Med. 175(1):217-225, 1992. This was the first ever humanized bispecific antibody.
  61. H.M. Shepard, G.D. Lewis, J.C. Sarup, B.M. Fendly, D. Maneval, J. Mordenti, I. Figari, C.E. Kotts, M.A. Palladino Jr., A. Ullrich, et al. Monoclonal antibody therapy of human cancer: taking the HER2 protooncogene to the clinic. J Clin Immunol. 11(3):117-27, 1991.
  62. G.K. Scott, J.M. Dodson, P.A. Montgomery, R.M. Johnson, J.C. Sarup, W.L. Wong, A. Ullrich, H.M. Shepard, and C.C. Benz. P185HER2signal transduction in breast cancer cell. J. Biol. Chem. 226(22): 14300-14305, 1991.
  63. J.C. Sarup, R.M. Johnson, K.L. King, B.M, Fendly, M.T. Lipari, M.A. Napier, A. Ullrich, H.M. Shepard. Characterization of an anti-p185HER2 monoclonal antibody that stimulates receptor function and inhibits tumor cell growth. Growth Regul.1(2): 72-82, 19. C. Sarup, R. M. Johnson, K. L. King, B. M. Fendly, M. T. Lipari, M. A. Napier, A. Ullrich, and H.M. Shepard. Characterization of an anti-p185HER2 monoclonal antibody that stimulates receptor function and inhibits tumor cell growth. Growth Regul. 1(2):72-82, 1991.
  64. H.M. Shepard, G.D. Lewis, J.C. Sarup, B.M. Fendly, D. Maneval, J. Mordenti. I. Figari, C.E. Kotts, M.A. Palladino, Jr., A. Ullrich, et al. Monoclonal antibody therapy of human cancer taking the HER2 protooncogene to the clinic. J. Clin. Immunol.11(3):117-127, 1991.
  65. S. Soomro, S. Shousha, P. Taylor, H.M. Shepard, and M. Feldmann. c-ErbB-2 expression in different histological types of invasive breast carcinoma. J.Clin.Pathol. 44(3):211-214, 1991.
  66. R. Kumar, H.M. Shepard, J. Mendelsohn. Regulation of phosphorylation of the c-ErbB- 2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol.Cell Biol. 11(2):979-986, 1991.
  67. M.H. Beresini, B.J. Sugarman, H.M. Shepard, L.B. Epstein. Synergistic induction of polypeptides by tumor necrosis factor and interferon-gamma in cells sensitive or resistant to tumor necrosis factor: assessment by computer based analysis of two-dimensional gels using the PDQUEST system. Electrophoresis 11(3):232-241, 1990.
  68. R.M. Hudziak, G.D. Lewis, W.E. Holmes, A. Ullrich, H.M. Shepard. Selection for transformation and met protooncogene amplification in NIH/3T3 fibroblasts using tumor necrosis factor- . Cell Growth Differ. 1(3):129-134, 1990. Paper that suggests macrophages might be important in amplification of proto-oncogenes in early stage tumors.
  69. B.M. Fendly, C. Kotts, D. Vetterlein, G.D. Lewis, M. Winget, M.E. Carver, S.R. Watson, J. Sarup, S. Saks, A. Ullrich, H.M. Shepard. The extracellular domain of HER2/neu is a potential immunogen for active specific immunotherapy of breast cancer. J.Biol.Response Mod. 9(5):449-455, 1990.
  70. R.M. Hudziak, G.D. Lewis, M. Winget, B.M. Fendly, H.M. Shepard, A. Ullrich. p185HER2monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol.Cell Biol. 9(3):1165-1172, 1989. Paper that started to convince others about HER2 as a target in cancer therapy.
  71. H.M. Shepard, G. D. Lewis. Resistance of tumor cells to tumor necrosis factor. J.Clin.Immunol. 8 (5):333-341, 1988.
  72. G. S. Feng, P. W. Gray, H. M. Shepard, M. W. Taylor. Antiproliferative activity of a hybrid protein between interferon-gamma and tumor necrosis factor. Science 241 (4872):1501-1503, 1988.
  73. R.M. Hudziak, G.D. Lewis, M.R. Shalaby, T.E. Eessalu, B.B. Aggrawal, A. Ullrich, H.M. Shepard. Amplified expression of the HER2/ErbB2 oncogene induces resistance to tumor necrosis factor in NIH/3T3 cells. Proc.Natl.Acad.Sci.U.S.A. 85(14):5102-5106, 1988. Paper that showed us that HER2 would be a good target.
  74. G.D. Lewis, B.B. Aggrawal, T.E. Eessalu, B.J. Sugarman, H.M. Shepard. Modulation of the growth of transformed cells b human tumor necrosis factor- and interferon-gamma. Cancer Res. 47(20):5382-5385-1987.
  75. S.J. Liebovich, P.J. Polverini, H.M. Shepard, D.M. Wiseman, V. Shively, Nuseir. Macrophage-induced angiogenesis is mediated by tumor necrosis factor. Nature. 329(6140):630-632, 1987.
  76. R.M. Locksley, F.P. Heinzel, H.M. Shepard, J. Agosti, T.E. Eessalu, B.B. Aggrawal, J.M. Harlan. Tumor necrosis factors differ in their capacities to generate interleukin 1 release from human endothelial cells. J. Immunol. 139(6): 1891-1895, 1987.
  77. J. E. Talmadge, O. Bowersox, H. Tribble, S.H. Lee, H. M. Shepard, D. Liggitt. Toxicity of tumor necrosis factor is synergistic with gamma-interferon and can be reduced with cyclooxygenase inhibitors. Am.J.Pathol. 128(3):410-425, 1987.
  78. T. Espevik, I. S. Figari, M.R. Shalaby, G.A. Lackides, G.D. Lewis, H.M. Shepard, M. Palladino, Jr. Inhibition of cytokine production by cyclosporin A and transforming growth factor- J.Exp.Med. 166(2):571-576, 1987.
  79. M.R. Shalaby, M.A. Palladino, Jr., S.E. Hirabayashi, T.E. Eessalu, G.D. Lewis, H.M. Shepard, B.B. Aggarwal. Receptor binding and activation of polymorphonuclear neutrophils by tumor necrosis factor. J.Leukoc.Biol. 41(3):196-204, 1987.
  80. B.J. Sugarman, G.D. Lewis, T.E. Eessalu, B.B. Aggarwal, H.M. Shepard. Effects of growth factors on the antiproliferative activity of tumor necrosis factors. Cancer Res. 47(3):780-786, 1987. This is the paper that took us to HER2 as a target.
  81. D. V. Goeddel, B. B. Aggarwal, P. W. Gray, D. W. Leung, G. E. Nedwin, M. A. Palladino, J. S. Patton, D. Pennica, H. M. Shepard, B. J. Sugarman, et al. Tumor necrosis factors: gene structure and biological activities. Cold Spring Harb.Symp.Quant.Biol. 51 Pt 1:597-609, 1986.
  82. G. M. Malacinski, C. C. Simonsen, H. M. Shepard (editors). Molecular Genetics of Mammalian Cells. Primers in Developmental Biology, (Macmillan, London, 1986).
  83. J.S. Patton, H. M. Shepard, H. Wilking, G. Lewis, B. B. Aggarwal, T. E. Eessalu, L. A. Gavin, C. Grunfeld. Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells. Proc.Natl.Acad.Sci.U.S.A 83(21):8313-8317, 1986.
  84. J. L. Urban, H. M. Shepard, J. L. Rothstein, B. J. Sugarman, H. Schreiber. Tumor necrosis factor: a potent effector molecule for tumor cell killing by activated macrophages. Proc.Natl.Acad.Sci.U.S.A 83(14):5233-5237, 1986.
  85. B.J. Sugarman, B. B. Aggarwal, P. E. Hass, I. S. Figari, M. A. Palladino, Jr., H. M. Shepard. Recombinant human tumor necrosis factor- : effects on proliferation of normal and transformed cells in vitro. Science 230(4728):943-945, 1985.
  86. D. J. Capon, H. M. Shepard, D. V. Goeddel. Two distinct families of human and bovine interferon- genes are coordinately expressed and encode functional polypeptides. Mol.Cell Biol. 5(4):768-779, 1985.
  87.  L. P. Svedersky, H. M. Shepard, S. A. Spencer, M. R. Shalaby, M. A. Palladino. Augmentation of human natural cell-mediated cytotoxicity by recombinant human interleukin 2. J.Immunol. 133(2):714-718, 1984.
  88.  H. A. de Boer, H. M. Shepard. Strategies for optimizing foreign gene expression in Escherichia coli. Horiz.Biochem.Biophys. 7:205-248, 1983.
  89. E. Franke, H. M. Shepard, C. M. Houck, D. W. Leung, D. V. Goeddel, R. M. Lawn. Carboxyterminal region of hybrid leukocyte interferons affects antiviral specificity. DNA 1(3):223- 230, 1982.
  90. H. M. Shepard, E. Yelverton, D. V. Goeddel. Increased synthesis in E. coli of fibroblast and leukocyte interferons through alterations in ribosome binding sites. DNA 1(2):125-131, 1982.
  91. H. M. Shepard, D. Leung, N. Stebbing, D. V. Goeddel. A single amino acid change in IFN- 1 abolishes its antiviral activity. Nature 294(5841):563-565, 1981.
  92. P. K. Weck, S. Apperson, N. Stebbing, P. W. Gray, D. Leung, H. M. Shepard, D. V. Goeddel. Antiviral activities of hybrids of two major human leukocyte interferons. Nucleic Acids Res. 9(22):6153-6166, 1981.
  93. M. Muesing, J. Tamm, H. M. Shepard, B. Polisky. A single base-pair alteration is responsible for the DNA overproduction phenotype of a plasmid copy-number mutant. Cell 24(1):235-242, 1981.
  94. D. V. Goeddel, H. M. Shepard, E. Yelverton, D. Leung, R. Crea, A. Sloma, and S. Pestka. Synthesis of human fibroblast interferon by E. coli. Nucleic Acids Res. 8(18):4057-4074, 1980.
  95. H. M. Shepard, D. H. Gelfand, B. Polisky. Analysis of a recessive plasmid copy number mutant: evidence for negative control of Col E1 replication. Cell 18(2):267-275, 1979.
  96. H.M. Shepard, B. Polisky. Measurement of Plasmid copy number. Methods Enzymol. 68:503-513, 1979.
  97. D. H. Gelfand, H. M. Shepard, P. H. O'Farrell, B. Polisky. Isolation and characterization of ColE1-derived plasmid copy-number mutant. Proc.Natl.Acad.Sci.U.S.A 75(12):5869-5873, 1978.

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