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Department of Medicinal Chemistry and Molecular Pharmacology Personnel - David J. Riese

David J. Riese, Ph.D.
Adjunct Professor of Medicinal Chemistry and Molecular Pharmacology

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Specialization: ErbB Receptor Signal Transduction in Human Malignancies


A.B. - 1987 - Wabash College
M.Phil. - 1989 - Yale University (Human Genetics)
Ph.D. - 1993 - Yale University (Genetics)
Postdoc - 1993-97 - Yale University (Pathology)

Research: ErbB Receptor Signal Transduction in Human Malignancies

OVERVIEW - Our group studies the Epidermal Growth Factor (EGF) family of peptide hormones and their receptors, the ErbB family of receptor tyrosine kinases. This network plays a significant role in regulating the proliferation and differentiation of epithelial cells. Moreover, deregulated signaling by this network is a causative event in many human tumors, and contributes to increased tumor cell invasiveness, metastatic potential, and chemoresistance. Consequently, our group studies this signaling network with the ultimate goal being the development of novel cancer diagnostic and treatment strategies.  Citations in this section refer to publications listed below.

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]. 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].

EGF FAMILY HORMONES - In collaboration with Mark Lemmon (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 identifying factors that regulate the affinity, potency, and efficacy of EGF family hormones [13, 17, 20, 21, 23, 24, 29, 30, 32, 34, 36, 39, 40, 42, 43, 45, 46].  We are also interested in elucidating the structural features of EGF family hormones that are responsible for differences in affinity, potency, and efficacy. Recently we have discovered that some EGF family hormones can antagonize the activity of other EGF family hormones and that single amino acid substitutions can be sufficient to change an agonist to an antagonist and vice versa. Thus, these studies have the potential to yield new cancer therapies.

EGFR MUTANTS 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, BC3]. We are also investigating the mechanisms by which these EGFR mutants contribute to tumor cell invasion an 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, BC4].

NOTE - Dr. Riese is now a member of the faculty at the Auburn University Harrison School of Pharmacy. For more information about his work, please visit

Honors and Credentials

Predoctoral Fellowship, Howard Hughes Medical Institute (1988-93)
Postdoctoral Fellowship, Department of Defense Breast Cancer Research Program (1994-97)
Henry W. Heine Award for Excellence in Undergraduate Teaching, Purdue School of Pharmacy (2000)
Career Development Award, Department of Defense Breast Cancer Research Program (2000-04)
New Investigator Award, Department of Defense Prostate Cancer Research Program (2002-05)
Purdue/Lafayette Lions Club Cancer Research Award (2010)


"Regulation of ErbB4 Signaling by Neuregulin Isoforms", NIH R01CA114209
08/01/2006 - 07/31/2012 (NCE), Principal Investigator.

Administration and Committee Work

Editorial Advisory Board, Biochemical Journal

Editorial Board, Breast Cancer - Targets and Therapy

Editorial Board, Advances in Biological Chemistry

Representative Publications


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.

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.

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.

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.

21.  JL Gilmore and DJ Riese II. secErbB4-26/549 antagonizes ligand-induced ErbB4 tyrosine phosphorylation.  Oncol Res 14: 589-602 (2004). PMID: 15667000.

23.   SS Hobbs, RM Gallo, and DJ Riese II.  Phe45 of NRG2β is critical for the affinity of NRG2b for ErbB4 and for potent stimulation of ErbB4 signaling by NRG2b.  Growth Factors 23: 273-283 (2005). PMID: 16338790.

24.   JL Gilmore, RM Gallo, and DJ Riese II.  The EGFR-S442F mutant displays increased affinity for Neuregulin2β and agonist-independent coupling to downstream signaling events.  Biochem J  396: 79-88 (2006). PMID: 16445385.  PMCID: 1450006.

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.  PMCID: 1618953.

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.  PMCID: 2788506.

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. PMCID: 2789424.

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. PMCID: 2882853.

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.  PMCID: 2730887.

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.  PMCID: 2094732.

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.  PMCID: 2435050.

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. PMCID: 2764248.

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.  PMCID: 2517605.

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.  PMCID: 2632975.

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.  PMCID: 2665203.

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.  PMCID: 2784013.

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. PMCID: 2991402.

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.  PMCID: 3022118.

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.  PMCID: 3083243.

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.  Free PMC Article.

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.  Free PMC Article.

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, in press. PMID: 22260327.  PMCID: In process.

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: xxxxxxxx. PMCID: In process.



BC3.  RM Gallo and DJ Riese II.  "Activating Mutations of ErbB Family Receptor Tyrosine Kinases."  In: Recent Progress in Cancer Research, C.K. Tang, ed.  Transworld Research Network, Kerala, India (2007).  ISBN: 81-7895-253-X.

BC4.  NK Nickerson, JL Gilmore, KT Allen, DJ Riese II, KP Nephew and J Foley. "EGFR Ligand-Specific Signaling in Breast Cancer Metastasis: Recurring Developmental Themes." In: Breast Cancer – Carcinogenesis, Cell Growth, and Signalling Pathways, Mehmet Gunduz and Esra Gunduz, eds.  Intech Publishing, Rijeka, Croatia (2011).  ISBN: 978-953-307-714-7.

Curriculum Vitae

Click here for a full CV for David J. Riese. (an Adobe Acrobat file)

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