OVERVIEW – We study the Epidermal Growth Factor (EGF) family of peptide hormones and their receptors, the ErbB receptor tyrosine kinases. This network regulates the proliferation and differentiation of epithelial cells. Deregulated signaling by this network contributes to human tumorigenesis and increased tumor cell invasiveness, metastatic potential, and chemoresistance. Consequently, our ultimate goal is the development of novel cancer treatments. Citations in this section refer to the publication list below. For additional information about our work, please visit http://www.davidriese.com.
ERBB4 AND EPITHELIAL TUMORS - ErbB4 expression is lost in many epithelial tumors, suggesting that ErbB4 is a tumor suppressor in these tissues. Indeed, a constitutively active, ligand independent ErbB4 mutant inhibits clonigenic proliferation by human breast, pancreatic, and prostate tumor cell lines [19, 25, 26, 41, 50]. However, other data indicate that ErbB4 is coupled to tumor cell proliferation, motility, and invasiveness [41, 44]. We are using various expression systems, analytical approaches, ErbB4 ligands, and ErbB4 mutants to characterize ErbB4 coupling to tumor suppression and malignant phenotypes. We are focused on deciphering the mechanisms by which ErbB4 can be coupled to these divergent responses [13, 25, 26, 31, 32, 41, 43, 44, 50]. We are also pursuing the discovery and development of novel ErbB4 agonists and antagonists that can be used to pharmacologically probe ErbB4 function in human malignancies and hold potential for the treatment of ErbB4-dependent tumors [30, 36, 42, 46].
EGF FAMILY HORMONES - In collaboration with Mark Lemmon (University of Pennsylvania), Kathryn Ferguson (University of Pennsylvania), Stephen Ethier (Wayne State University), John Foley (Indiana University), Anne Lykkesfeldt (Danish Cancer Institute), James Leary (Purdue University), Laurie Parker (Purdue University) and Claudio Aguilar (Purdue University), we are characterizing the biological activities of EGF family hormones and we are identifying factors that regulate the affinity, potency, and efficacy of these peptide growth factors [13, 17, 20, 21, 23, 24, 29, 30, 32, 34, 36, 39, 40, 42, 43, 45, 46, 48, 51]. We are also interested in elucidating the structural features of EGF family hormones that are responsible for differences in affinity, potency, and efficacy.
EGFR AND HUMAN MALIGNANCIES - In collaboration with Jeffrey Settleman (Genentech) and John Foley (Indiana University), we are investigating the mechanisms by which EGFR mutants contribute to chemosensitivity and chemoresistance in non-small-cell lung carcinoma (NSCLC) [27, 28, 33]. We are also investigating the mechanisms by which these EGFR mutants contribute to tumor cell invasion and metastasis. We are focusing on the role that ligand-induced EGFR heterodimerization with other ErbB receptors may play in these processes. Finally, we are investigating the roles that ligand-induced EGFR signaling plays in the colonization of bone by lung and breast tumor cells [29, 39, 40, 47].
PEER-REVIEWED JOURNAL ARTICLES (Selected of 51)
A complete list of of my publications can be found at my personal web site (http://www.davidriese.com/publications) and at PubMed (http://www.ncbi.nlm.nih.gov/pubmed/?term=riese+dj). My Google Scholar profile can be found here (http://scholar.google.com/citations?user=55j1ZOEAAAAJ&hl=en&oi=ao).
#Indicates a publication that contributes to the Google Scholar i10-Index.
*Indicates a publication that contributes to the Google Scholar H-index
#*13. C Sweeney, C Lai, DJ Riese II, AJ Diamonti, LC Cantley, and KL Carraway III. Ligand discrimination in signaling through an ErbB4 receptor homodimer. J Biol Chem 275: 19803-19807 (2000). PMID: 10867024. Personal Copy http://tinyurl.com/68h6oha
#*17. SS Hobbs, SL Coffing, ATD Le, EM Cameron, EE Williams, M Andrew, EN Blommel, RP Hammer, H Chang, and DJ Riese II. Neuregulin isoforms exhibit distinct patterns of ErbB family receptor activation. Oncogene 21: 8442-8452 (2002). PMID: 12466964. Personal Copy http://tinyurl.com/4wg5d2g
#*19. EE Williams, LJ Trout, RM Gallo, SE Pitfield, DJ Penington, I Bryant, and DJ Riese II. A constitutively-active ErbB4 mutant inhibits drug-resistant colony formation by the DU-145 and PC-3 human prostate tumor cell lines. Cancer Lett 192: 67-74 (2003). PMID: 12637154. Personal Copy http://tinyurl.com/5s89b8j
#20. SS Hobbs, EM Cameron, RP Hammer, ATD Le, RM Gallo, EN Blommel, SL Coffing, and DJ Riese II. Five carboxyl-terminal residues of Neuregulin2 are critical for stimulation of signaling by the ErbB4 receptor tyrosine kinase. Oncogene 23: 883-894 (2004). PMID: 14661053. Personal Copy http://tinyurl.com/69cu4xr
21. JL Gilmore and DJ Riese II. secErbB4-26/549 antagonizes ligand-induced ErbB4 tyrosine phosphorylation. Oncol Res 14: 589-602 (2004). PMID: 15667000. Personal Copy http://tinyurl.com/6c6a7vg
23. SS Hobbs, RM Gallo, and DJ Riese II. Phe45 of NRG2 is critical for the affinity of NRG2 for ErbB4 and for potent stimulation of ErbB4 signaling by NRG2. Growth Factors 23: 273-283 (2005). PMID: 16338790. Personal Copy http://tinyurl.com/4nacmvz
#24. JL Gilmore, RM Gallo, and DJ Riese II. The EGFR-S442F mutant displays increased affinity for Neuregulin2 and agonist-independent coupling to downstream signaling events. Biochem J 396: 79-88 (2006). PMID: 16445385. Personal Copy http://tinyurl.com/4smxy5s
#25. RM Gallo, I Bryant, R Fry, EE Williams, and DJ Riese II. Phosphorylation of ErbB4 on Tyr1056 is critical for inhibition of colony formation by prostate tumor cell lines. Biochem Biophys Res Com 349: 372-382 (2006). PMID: 16934755. Personal Copy http://tinyurl.com/5rytyyo
#26. SE Pitfield, I Bryant, DJ Penington, G Park, and DJ Riese II. Phosphorylation of ErbB4 on tyrosine 1056 is critical for ErbB4 coupling to inhibition of colony formation by human mammary cell lines. Oncol Res 16: 179-193 (2006). PMID: 17120616. Personal Copy http://tinyurl.com/46jj7q7
#*27. DJ Riese II, RM Gallo, and J Settleman. Mutational activation of ErbB receptor tyrosine kinases: Insights into mechanisms of signal transduction and tumorigenesis. Bioessays 29: 558-565 (2007). PMID: 17508401. Personal Copy http://tinyurl.com/4qa42hp
#*28. N Godin-Heymann, I Bryant, MN Rivera, L Ulkus, DW Bell, DJ Riese II, J Settleman, and DA Haber. Oncogenic activity of EGFR kinase mutant alleles is enhanced by the T790M drug resistance mutation. Cancer Res 67: 7319-7326 (2007). PMID: 17671201. Personal Copy http://tinyurl.com/4ehfeox
#*29. JL Gilmore, JA Scott, Z Bouizar, A Robling, SE Pitfield, DJ Riese II, and J Foley. Amphiregulin-EGFR signaling regulates PTHrP gene expression in breast cancer cells. Breast Cancer Res Treat 110: 493-505 (2008). PMID: 17882547. Personal Copy http://tinyurl.com/4ko56ch
30. KJ Wilson, CP Mill, EM Cameron, SS Hobbs, RP Hammer, and DJ Riese II. Interconversion of Neuregulin2 full and partial agonists for ErbB4. Biochem Biophys Res Com 364: 351-357 (2007). PMID: 17945187. Personal Copy http://tinyurl.com/4ka7lxq
31. RM Gallo and DJ Riese II. The antibody sc-33040-R fails to specifically recognize phosphorylation of ErbB4 on tyrosine 1056. Growth Factors 25: 329-333 (2007). PMID: 18236211. Personal Copy http://tinyurl.com/4p25p5m
#*32. T Frogne, RV Benjaminsen, K Sonne-Hansen, BS Sorensen, E Nexo, A-V Laenkholm, LM Rasmussen, DJ Riese II, P de Cremoux, J Stenvang, and AE Lykkesfeldt. Activation of ErbB3, EGFR, and Erk is essential for growth of human breast cancer cell lines with acquired resistance to fulvestrant. Breast Cancer Res Treat 114: 263-275 (2009). PMID: 18409071. Personal Copy http://tinyurl.com/46egf7q
#*33. SM Rothenberg, JA Engelman, S Le, DJ Riese II, DA Haber, and J Settleman. Modeling oncogene addiction with RNA interference. Proc Natl Acad Sci USA 105: 12480-12484 (2008). PMID: 18711136. Personal Copy http://tinyurl.com/4off42o
#*34. NE Willmarth, A Baillo, ML Dziubinski, K Wilson, DJ Riese II, and SP Ethier. Altered EGFR localization and degradation in human breast cancer cells with an amphiregulin/EGFR autocrine loop. Cell Signal 21: 212-219 (2009). PMID: 18951974. Personal Copy http://tinyurl.com/4q6zeum
#*36. KJ Wilson, JL Gilmore, J Foley, MA Lemmon, and DJ Riese II. Functional selectivity of EGF Family Peptide Growth Factors: Implications for Cancer. Pharmacol Ther 122: 1-8 (2009). PMID: 19135477. Personal Copy http://tinyurl.com/4jsglyv
#39. JL Gilmore, RM Gonterman, K Menon, G Lorch, DJ Riese II, A Robling, and J Foley. Reconstitution of amphiregulin-EGFR signaling in lung squamous carcinomas activates PTHrP gene expression and cancer-mediated diseases of the bone. Mol Cancer Res 7: 1714-1728 (2009). PMID: 19825997. Personal Copy http://tinyurl.com/4ozf3ox
#*40. J Foley, NK Nickerson, S Nam, KT Allen, JL Gilmore, KP Nephew, and DJ Riese II. EGFR signaling in breast cancer: Bad to the bone? Sem Cell Dev Biol 21: 951-960 (2010). PMID 20813200. Personal Copy http://tinyurl.com/66xttg2
#41. CP Mill, K Gettinger, and DJ Riese II. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines. Exp Cell Res 317: 392-404 (2011). PMID: 21110957. Personal Copy http://tinyurl.com/63xebh5
42. DJ Riese II. Ligand-based receptor tyrosine kinase partial agonists: New paradigm for cancer drug discovery? Expert Opin Drug Disc 6: 185-193 (2011). PMID: 21532939. Personal Copy http://tinyurl.com/65jhomr
#43. MD Zordan, CP Mill, DJ Riese II, and JF Leary. A high-throughput, interactive imaging, bright-field wound healing assay. Cytometry A 79A: 227-232 (2011). PMID: 22045642. Personal Copy http://tinyurl.com/47ur49r
44. CP Mill, MD Zordan, SM Rothenberg, J Settleman, JF Leary, and DJ Riese II. ErbB2 is necessary for ErbB4 ligands to stimulate oncogenic activities in models of human breast cancer. Genes & Cancer 2: 792-804 (2011). PMID: 22393464. Personal Copy http://tinyurl.com/7tbr684
#45. KJ Wilson, CP Mill, S Lambert, J Buchman, TR Wilson, V Hernandez-Gordillo, RM Gallo, Laura MC Ades, J Settleman, and DJ Riese II. EGFR ligands exhibit functional differences in models of paracrine and autocrine signaling. Growth Factors 30: 107-116 (2012). PMID: 22260327. Personal Copy http://tinyurl.com/d2ua4wf
46. KJ Wilson, CP Mill, RM Gallo, EM Cameron, H VanBrocklin, J Settleman, and DJ Riese II. The Q43L mutant of Neuregulin 2beta is a pan-ErbB receptor antagonist. Biochem J 443: 133-144 (2012). PMID: 22216880. Personal Copy http://tinyurl.com/6og7coh
47. J Foley, NK Nickerson, DJ Riese II, PC Hollenhorst, G. Lorch, and AM Foley. At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of the bone. Odontology 100: 109-129 (2012). PMID: 22684584. Personal Copy http://tinyurl.com/d8mxuoo
48. NK Nickerson, CP Mill, HJ Wu, DJ Riese II, and J Foley. Autocrine-derived epidermal growth factor receptor ligands contribute to recruitment of tumor-associated macrophage and growth of basal breast cancer cells in vivo. Oncol Res 20: 303-17 (2013). PMID: 23879171. Personal Copy http://tinyurl.com/qg239gx
50. RM Gallo, IN Bryant, CP Mill, S Kaverman, and DJ Riese II. Multiple functional motifs are required for the tumor suppressor activity of a constitutively-active ErbB4 mutant. J Cancer Res Ther Oncol 1: 104 (2013). PMID: 24791013. Personal Copy http://tinyurl.com/nygnyg8
51. DJ Riese II and RL Cullum. Epiregulin: Roles in Normal Physiology and Cancer. Sem Cell Dev Biol. In press. doi: 10.1016/j.semcdb.2014.03.005. PMID 24631357.