Research Summary

The Herman lab's work explores the importance and clinical utility of epigenetic changes in cancer. In earlier work, they developed a simple and sensitive method, methylation- specific PCR, for the detection of methylation changes. It is the most widely used method for the study of methylation changes in cancer. This approach, and others developed in the lab, is now used to identify new genes that are silenced in cancer. The Herman lab also continues to examine methylation events in pre-invasive lesions associated with solid tumors to understand tumor development and progression and to develop these findings into early detection markers. The Herman lab also has explored the use of gene methylation as predictive and prognostic markers in cancer. Both in the lab and in a phase 1 trial, Herman has studied approaches to reverse gene silencing in patients with cancer.

Journal Citations

Bailey, V.J.; Easwaran, H.; Zhang, Y.; Griffiths, E.; Belinsky, S.A.; Herman, J.G.; Baylin, S.B.; Carraway, H.E.; Wang, T.H. MS-qFRET: a quantum dot-based method for analysis of DNA methylation. Genome Res. 2009 Aug;19(8):1455-1461.

Chen, L.; Gallicchio, L.; Boyd-Lindsley, K.; Tao, X.G.; Robinson, K.A.; Lam, T.K.; Herman, J.G.; Caulfield, L.E.; Guallar, E.; Alberg, A.J. Alcohol consumption and the risk of nasopharyngeal carcinoma: a systematic review. Nutr Cancer. 2009;61(1):1-15.

Emens, L.A.; Asquith, J.M.; Leatherman, J.M.; Kobrin, B.J.; Petrik, S.; Laiko, M.; Levi, J.; Daphtary, M.M.; Biedrzycki, B.; Wolff, A.C.; Stearns, V.; Disis, M.L.; Ye, X.; Piantadosi, S.; Fetting, J.H.; Davidson, N.E.; Jaffee, E.M. Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J Clin Oncol. 2009 Dec 10;27(35):5911-5918.

Fandy, T.E.; Herman, J.G.; Kerns, P.; Jiemjit, A.; Sugar, E.A.; Choi, S.H.; Yang, A.S.; Aucott, T.; Dauses, T.; Odchimar-Reissig, R.; Licht, J.; McConnell, M.J.; Nasrallah, C.; Kim, M.K.; Zhang, W.; Sun, Y.; Murgo, A.; Espinoza-Delgado, I.; Oteiza, K.; Owoeye, I.; Silverman, L.R.; Gore, S.D.; Carraway, H.E. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. Blood. 2009 Sep 24;114(13):2764-2773.

Glockner, S.C.; Dhir, M.; Yi, J.M.; McGarvey, K.E.; Van Neste, L.; Louwagie, J.; Chan, T.A.; Kleeberger, W.; de Bruine, A.P.; Smits, K.M.; Khalid-de Bakker, C.A.; Jonkers, D.M.; Stockbrugger, R.W.; Meijer, G.A.; Oort, F.A.; Iacobuzio-Donahue, C.; Bierau, K.; Herman, J.G.; Baylin, S.B.; Van Engeland, M.; Schuebel, K.E.; Ahuja, N. Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer. Cancer Res. 2009 Jun 1;69(11):4691-4699.

Licchesi, J.D.; Herman, J.G. Methylation-specific PCR. Methods Mol Biol. 2009;507:305-323.

Lin, J.; Gilbert, J.; Rudek, M.A.; Zwiebel, J.A.; Gore, S.; Jiemjit, A.; Zhao, M.; Baker, S.D.; Ambinder, R.F.; Herman, J.G.; Donehower, R.C.; Carducci, M.A. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin Cancer Res. 2009 Oct 1;15(19):6241-6249.

Rudin, C.M.; Avila-Tang, E.; Harris, C.C.; Herman, J.G.; Hirsch, F.R.; Pao, W.; Schwartz, A.G.; Vahakangas, K.H.; Samet, J.M. Lung cancer in never smokers: molecular profiles and therapeutic implications. Clin Cancer Res. 2009 Sep 15;15(18):5646-5661.

Wang, J.S.; Guo, M.; Montgomery, E.A.; Thompson, R.E.; Cosby, H.; Hicks, L.; Wang, S.; Herman, J.G.; Canto, M.I. DNA promoter hypermethylation of p16 and APC predicts neoplastic progression in Barrett's esophagus. Am J Gastroenterol. 2009 Sep;104(9):2153-2160.

Ye, Y.; McDevitt, M.A.; Guo, M.; Zhang, W.; Galm, O.; Gore, S.D.; Karp, J.E.; Maciejewski, J.P.; Kowalski, J.; Tsai, H.L.; Gondek, L.P.; Tsai, H.C.; Wang, X.; Hooker, C.; Smith, B.D.; Carraway, H.E.; Herman, J.G. Progressive chromatin repression and promoter methylation of CTNNA1 associated with advanced myeloid malignancies. Cancer Res. 2009 Nov 1;69(21):8482-8490.

Zhang, Y.; Bailey, V.; Puleo, C.M.; Easwaran, H.; Griffiths, E.; Herman, J.G.; Baylin, S.B.; Wang, T.H. DNA methylation analysis on a droplet-in-oil PCR array. Lab Chip. 2009 Apr 21;9(8):1059-1064.

Bailey, V.J.; Keeley, B.P.; Zhang, Y.; Ho, Y.P.; Easwaran, H.; Brock, M.V.; Pelosky, K.L.; Carraway, H.E.; Baylin, S.B.; Herman, J.G.; Wang, T.H. Enzymatic incorporation of multiple dyes for increased sensitivity in QD-FRET sensing for DNA methylation detection. Chembiochem. 2010 Jan 4;11(1):71-74.

Bailey, V.J.; Zhang, Y.; Keeley, B.P.; Yin, C.; Pelosky, K.L.; Brock, M.; Baylin, S.B.; Herman, J.G.; Wang, T.H. Single-tube analysis of DNA methylation with silica superparamagnetic beads. Clin Chem. 2010 Jun;56(6):1022-1025.

Easwaran, H.P.; Van Neste, L.; Cope, L.; Sen, S.; Mohammad, H.P.; Pageau, G.J.; Lawrence, J.B.; Herman, J.G.; Schuebel, K.E.; Baylin, S.B. Aberrant silencing of cancer-related genes by CpG hypermethylation occurs independently of their spatial organization in the nucleus. Cancer Res. 2010 Oct 15;70(20):8015-8024 NIHMSID # 263537 PMCID Journal: In process.

Griffiths, E.A.; Gore, S.D.; Hooker, C.; McDevitt, M.A.; Karp, J.E.; Smith, B.D.; Mohammad, H.P.; Ye, Y.; Herman, J.G.; Carraway, H.E. Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylation. Leuk Lymphoma. 2010 Sep;51(9):1711-1719

Healey, M.A.; Deaton, S.L.; Alder, J.K.; Winnepenninckx, V.; Casero, R.A., Jr.; Herman, J.G. Id1 overexpression is independent of repression and epigenetic silencing of tumor suppressor genes in melanoma. Epigenetics. 2010 Jul 1;5(5):410-421

Jia, Y.; Yang, Y.; Liu, S.; Herman, J.G.; Lu, F.; Guo, M. SOX17 antagonizes WNT/beta-catenin signaling pathway in hepatocellular carcinoma. Epigenetics. 2010 Nov-Dec;5(8):743-749

Middeldorf, I.; Galm, O.; Osieka, R.; Jost, E.; Herman, J.G.; Wilop, S. Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML). Am J Hematol. 2010 Jul;85(7):477-481

Noushmehr, H.; Weisenberger, D.J.; Diefes, K.; Phillips, H.S.; Pujara, K.; Berman, B.P.; Pan, F.; Pelloski, C.E.; Sulman, E.P.; Bhat, K.P.; Verhaak, R.G.; Hoadley, K.A.; Hayes, D.N.; Perou, C.M.; Schmidt, H.K.; Ding, L.; Wilson, R.K.; Van Den Berg, D.; Shen, H.; Bengtsson, H.; Neuvial, P.; Cope, L.M.; Buckley, J.; Herman, J.G.; Baylin, S.B.; Laird, P.W.; Aldape, K. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010 May 18;17(5):510-522.

Savic, S.; Franco, N.; Grilli, B.; Barascud Ade, V.; Herzog, M.; Bode, B.; Loosli, H.; Spieler, P.; Schonegg, R.; Zlobec, I.; Clark, D.P.; Herman, J.G.; Bubendorf, L. Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology. Chest. 2010 Jul;138(1):137-144

van Vlodrop, I.J.; Baldewijns, M.M.; Smits, K.M.; Schouten, L.J.; van Neste, L.; van Criekinge, W.; van Poppel, H.; Lerut, E.; Schuebel, K.E.; Ahuja, N.; Herman, J.G.; de Bruine, A.P.; van Engeland, M. Prognostic significance of Gremlin1 (GREM1) promoter CpG island hypermethylation in clear cell renal cell carcinoma. Am J Pathol. 2010 Feb;176(2):575-584.

Veeck, J.; Ropero, S.; Setien, F.; Gonzalez-Suarez, E.; Osorio, A.; Benitez, J.; Herman, J.G.; Esteller, M. BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors. J Clin Oncol. 2010 Oct 10;28(29):e563-564; author reply e565-566