Cancer, prostate cancer, breast cancer, Biophysics
Fellow, Collage of American Pathologists.
Study Section Member, USDVA, 1995-99.
Study Section Member, NIH NCI, 2004-2006.
Headed multi-institutional U01 grant programs of the NCI on prostate cancer research 1999-2017.
1970-1974, Post Doctoral Fellow, Chemical Crystallography, Oxford University, with Prof. Dorothy Crowfoot Hodgkin. Crystal Structure of Ultralente (4 zinc) Insulin.
The major focus of our research is on prostate cancer and breast cancer in particular the identification of gene signatures useful for diagnosis, prognosis, and the understanding of mechanism. The approach has been to combine previous training and research in biophysics with previous training and practice of pathology to investigate molecular mechanisms of disease. Early studies used spectroscopy and protein crystallography to study the mechanism of insulin action and muscle contraction progressing to prostate and breast cancer. A novel analytical method was developed to resolving global gene expression data of prostate cancer into gene expression by the four major cell-type contributions, tumor cells, normal epithelial cells, stroma cells, and BPH cells. Another novel aspect has been the recognition that gene expression changes in the tumor adjacent stroma, a component necessary for tumor formation, may be used to develop highly accurate multigene profiles (classifiers) for diagnosis and for prognosis for patients treated by prostatectomy. Recently working with Dr. Kathleen McGuire, we have realized that hundreds of gene expression changes in the stroma of prostate cancer of African Americans is explaining the deficient immune response which may be related to the aggressive phenotype of prostate cancer in African Americans. A prognostic classifier for African Americans is being developed. To facilitate translation of the gene profiles, the Regents of the University of California have sponsored four patent filings one of which is issued and has provided a license to the biotechnology startup, Proveri Inc. for development of specific tests. Proveri Inc. has formed a co-development agreement with Koelis Inc., an MRI imagining company. The prostate cancer studies have led to the development of a prostate tissue biorepository and associated annotated database with over 2900 patients by informed consent, outcomes data, over 300 microarrays and a large TMA. Translational development of tests for African Americans is a major priority.
157. Rahmatpanah F, Agrawal S, Scarfone VM, Kapadia S, Mercola D, & Agrawal A (2018) Transcriptional Profiling of Age-Associated Gene Expression Changes in Human Circulatory CD1c+ Myeloid Dendritic Cell Subset. J Gerontol A Biol Sci Med Sci. 2018; Published online and as PMCID: PMC6298184. PMID: 29718193. https://www.ncbi.nlm.nih.gov/pubmed/29718193
132. Zhenyu Jia, Yipeng Wang, Yuanjie Hu, Christine McLaren, Yingyan Yu, Kai Ye, Xiao-Qin Xia, James A.
Koziol, Waldemar Lernhardt, Michael McClelland, Dan Mercola. A Sample Selection Strategy to Boost the
Statistical Power of Signature Detection In Cancer Expression Profile Studies. Bentham Science Publishers.
Anti-Cancer Agents in Medicinal Chemistry. 2012;13:203-211. Epublication, August 24, 2012.
PMID: 22934703; PMCID: PMC3786411.http://www.ncbi.nlm.nih.gov/pubmed/22934703
133. Zhenyu Jia, Farahnaz Rahmatpanah, Xin Chen, Waldemar Lernhardt, Yipeng Wang, Xiao-Qin Xia, Anne
Sawyers, Michael McClelland, and Dan Mercola. Expression changes in the stroma of prostate cancer predict subsequent relapse. PloS ONE 2012;7: Epublication 8/3/12. PMID: 22870216. PMCID:3411675.
134. Chen X, Xu S, McClelland M, Rahmatpanah F, Sawyers A, Jia Z, Mercola D. An accurate prostate cancer prognosticator using a seven-gene signature plus Gleason score and taking cell type heterogeneity into account. PLoS ONE 2012;7(9):e45178. doi: 10.1371/journal.pone.0045178. Epub 2012 Sep 28. PMCID 3460949; PMID 3460942. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23028830
135. Khan S, Jutzy JM, Valenzuela MM, Turay D, Aspe JR, Ashok A, Mirshahidi S, Mercola D, Lilly MB, Wall NR. Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer. PLoS
ONE. 2012;7(10):e46737. doi: 10.1371/journal.pone.0046737. Epub 2012 Oct 16. PubMed PMID: 23091600; PMCID: PMC3473028. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473028/
136. Lee C, Zhang Q, Zi X, Dash A, Soares MB, Rahmatpanah F, Jia Z, McClelland M, Mercola D. TGF-ß
Mediated DNA methylation in prostate cancer. Translational Andrology and Urology 2012;1(2):78-88.DOI: 0.3978/j.issn.2223-4683.2012.05.06. PMCID: 4131550.
137. Rahmatpanah F, Jia Z, Chen X, Jones FE, McClelland M, Mercola D. Expression of HER2 in Breast Cancer
Promotes a Massive Reorganization of Gene Activity and Suggests a Role for Epigenetic Regulation. J Data
Mining Genomics Proteomics. 2012;3: pii: e102. doi: 10.4172/2153-0602.1000e102. PMID: 24009986;
PubMed Central PMCID: PMC3760961.September 3, 2012. JDMGP an open access journal
138. Rebecca Pio, Zhenyu Jia, Veronique T. Baron, and Dan Mercola. Early Growth Response Gene 3 (Egr3) is
highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer. PloS ONE, 2013;
8: January 14, 2013. PMCID: PMC3544741; DOI 10.1371.
139. Matthew A. Kinseth, Zhenyu Jia, Farahnaz Rahmatpanah, Anne Sawyers, Manuel Sutton, Jessica Wang-
Rodriguez, Kathleen L. McGuire*, and Dan Mercola*. Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes. Int. J. Cancer, 2013;134 : 81-91.PMID:23754304; PMCID: PMC3800217. Online June 10, 2013, DOI: 0.1002/ijc.28326.
*Contributed equally. http://onlinelibrary.wiley.com/doi/10.1002/ijc.28326/pdf.
notice in MDLinx.com: http://www.mdlinx.com/oncology/news-article.cfm/4669757.*+Cpmytoniyrf
140. Chung Lee; Qiang Zhang, James Kozlowski, Charles Brendler, Marcelo B. Soares, Atreya Dash, Michael
McClelland, and Dan Mercola, Natural products and transforming growth factor-beta (TGF-ß) signaling in
cancer development and progression. Current Cancer Drug Targets. 2013; 13(5): 500-505. PMID:23597196.
ISSN (Print): 1568-0096, ISSN (Online): 1873-5576, DOI: 10.2174/15680096113139990034. June.
141. Xuejiao Tian, Saiyang Zhang, Hong-Min Liu, Yan-Bing Zhang, Christopher A Blair, Dan Mercola, Paolo
Sassone-Corsi and Xiaolin Zi. Histone Lysine-Specific Methyltransferases and Demethylases, in Carcinogenesis: New Targets for Cancer Therapy and Prevention. Current Cancer Drug Targets. 2013;13:558-579.PMID: 23713993; PMCID: PMC3703250.June. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703250/.
142. Yifei Chen, Zhenyu Jia, Dan Mercola and Xiaohui Xie, A gradient boosting algorithm for survival analysis via direct optimization of concordance index. Computational and Mathematical Methods in Medicine.Volume 2013, Article ID 873595, 8 pages, Hindawi Publishing Corp.,Epub 1/2013.PMCID: 2434876; PMID: 24348746.http://dx.doi.org/10.1155/20134/873595.
143. Zhenyu Jia, Michael Lilly, James A. Koziol, Xin Chen, Xiao-Qin Xia, Yipeng Wang, Douglas, Skarecky, Manuel Sutton, Anne Sawyers, Herb Ruckle, Philip Carpenter, Jessica-Wang Rodriquez, J. Jiang, Thomas Ahlering, Michael Kattan, and Dan Mercola. A method for generation of virtual controls for single arm prostate cancer adjuvant trials with application to a high risk cohort. PloS ONE, 9(1): e85010. doi:10.1371/journal.pone.0085010 Epublication January 21, 2014. PMCID: 3897405; PMID: 24465467.
144. Yokoyama NN, Shao S, Hoang BH, Mercola D (CPP), Zi X (CPP): Wnt signaling in castration-resistant prostate cancer: implications for therapy. Am J Clin Exp Urol 2014 2(1): 27-44. PMCID: 4135057; PMID 25143959.
145. Ponti, D., Bellenchi, G. C., Puca, R., Bastianelli, D., Maroder, M., Ragona, G., Roussel, P., Thiry, M. ,Mercola, D. and Calogero. The Transcription Factor EGR1 Localizes to the Nucleolus and Is Linked Suppression of Ribosomal Precursor Synthesis" Plos ONE, 2014; Epublication. PMCID: 4006901; PMID: 24787739. http://www.ncbi.nlm.nih.gov/pubmed/24787739 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006901/pdf/pone.0096037.pdf
146. Kinseth MA, Jia Z, Rahmatpanah F, Sawyers A, Sutton M, Wang-Rodriguez J,, McGuire KL (2014) Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes. International journal of cancer. Journal international du cancer 134(1):81-91. PMID 23754304, PMCID 3800217. http://www.ncbi.nlm.nih.gov/pubmed/23754304.
147. Chung Lee, Zhenyu Jia, Farahnaz Rahmatpanah, Qiang Zhang, Xiaolin Zi, Michael McClelland, and Dan Mercola. Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-ß and IGF Signaling. BioMed Research International. 2014; volume 2014: Epub, 8 pages, Article ID 502093 (review article). PMCID: PMC4095744.
148. Baron, V. T., Pio, R., Jia, Z., and Mercola, D. Early Growth Response 3 regulates genes of inflammation & directly activates IL6 & IL8 expression in prostate cancer. Br J Cancer 2015;112: 755-764;PMC4333488.
149. Chen, X., McClelland, M., Jia, Z., Rahmatpanah, F. B., Sawyers, A., Trent, J., Duggan, D., and Mercola, D. The identification of trans-associations between prostate cancer GWAS SNPs and RNA expression differences in tumor-adjacent stroma. Oncotarget 2015; 6: 1865-1873; PMC25638161.
150. Helfand, B. T., Roehl, K. A., Cooper, P. R., McGuire, B. B., Fitzgerald, L. M., Cancel-Tassin, G., Cornu, J. N., Bauer, S., Van Blarigan, E. L., Chen, X., Duggan, D., Ostrander, E. A., Gwo-Shu, M., Zhang, Z. F., Chang, S. C., Jeong, S., Fontham, E. T., Smith, G., Mohler, J. L., Berndt, S. I., McDonnell, S. K., Kittles, R., Rybicki, B. A., Freedman, M., Kantoff, P. W., Pomerantz, M., Breyer, J. P., Smith, J. R., Rebbeck, T. R., Mercola, D., Isaacs, W. B., Wiklund, F., Cussenot, O., Thibodeau, S. N., Schaid, D. J., Cannon-Albright, L., Cooney, K. A., Chanock, S. J., Stanford, J. L., Chan, J. M., Witte, J., Xu, J., Bensen, J. T., Taylor, J. A., and Catalona, W. J. Associations of prostate canceRisk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases. Human genetics 2015;134: 439-450; PMC25715684. http://www.ncbi.nlm.nih.gov/pubmed/25715684.
151. Rahmatpanah, F. B., Jia, Z., Chen, X., Char, J. E., Men, B., Franke, A. C., Jones, F. E., McClelland, M., and Mercola, D. A ccanlass of genes in the HER2 regulon that is poised for transcription in breast cancer cell lines and expressed in human breast tumors. Oncotarget 2015;6: 1286-130; PMC25428913. http://www.ncbi.nlm.nih.gov/pubmed/25428913.
152. Tian, Y., Choi, C. H., Li, Q. K., Rahmatpanah, F. B., Chen, X., Kim, S. R., Veltri, R., Chia, D., Zhang, Z., Mercola, D., and Zhang, H. Overexpression of periostin in stroma positively associated with aggressive prostate cancer. PLoS One 2015; 10: e0121502. PMC25781169. http://www.ncbi.nlm.nih.gov/pubmed/26043260.
153. Zhu, Jianguo, Cong Pan1, Jun Jiang, Mingsen Deng, Hengjun Gao, Bozhao Men, Michael McClelland, Dan Mercola, Wei-De Zhong and Zhenyu Jia. Six stroma-based RNA markers diagnostic for prostate cancer in European-Americans validated at the RNA and protein levels in patients in China. Oncotarget 2015;6:16757-65. 16:Epub. PMCID 4599350.
154. Li, X., Yokoyama, N. N., Zhang, S., Ding, L., Liu, H. M., Lilly, M. B., Mercola, D., and Zi, X. (2015) Flavokawain A induces deNEDDylation and Skp2 degradation leading to inhibition of tumorigenesis and cancer progression in the TRAMP transgenic mouse model. Oncotarget 6, 41809-41824, PMID 26497688, http://www.ncbi.nlm.nih.gov/pubmed/26497688.
155. vanDraanen, J. M.,. Davidson, H. Bour-Jordan, L. Bowman-Carpio1, D. Boyle3, S. Dubinett1, B. Gardner, J. Gardner, C. McFall, D. Mercola, T. Nakazono, S. Soares, H. Stoppler, M. Tempero, S. Vandenberg, Y.Y. Wan, S. Dry Assessing Researcher Needs for a Virtual Biobank. Biopreservation and Biobanking. 2016, DOI . 10.1089/bio.2016.0009; as print 2017;15:203-210.
156. Jia A, Lee, Chung, McClelland, Michael, Mercola, Dan. Tumor Microenvironment: Prospects for Diagnosis and Prognosis of Prostate Cancer Based on Changes in Tumor-Adjacent Stroma. Chapter 16, In: Mosquera, J. and Robinson, B., editors. Precision Molecular Pathology of Prostate Cancer, New York.: Springer-Nature, International Publishing. 2017, ISBN: 978-3-319-64094-5 ( in press).
MRI-19-601366 (D. Mercola) Jan 1, 2019 - Dec 31, 2021
UCOP University 0f California Office of the President
Development of the University of California-wide clinical genomic database
The major goal of this project is to work with four of the six UC medical centers to obtain genomic test results from providers of tests for all patients and combined with with the clinical records of UC patients in the UC Clinical Data Warehouse
1R01CA193967-01A1 (X. Zi) Jul 1, 2016 - Jun 30, 2021
The NEDD8 pathway mediated Skp2 degradation in chemoprevention of prostate cancer by FKA
The major goals of this project are to 1) Define mechanisms of FKA mediated Cullin1 deNEDDylation and Skp2 degradation; 2) Test the hypothesis that accumulation of Skp2 substrates is required for FKA mediated cell growth inhibition via cell cycle arrest and induction of apoptosis; 3) Perform pharmacokinetic/pharmacodynamics (PK/PD) and in vivo mechanistic studies on FKA mediated Skp2 degradation. Role: Co-investigator.
3U01CA086402-14S2 (I. Thompson) Jul 1, 2014 - Jun 30, 2020
San Antonio Center for Biomarkers of Risk for Prostate Cancer (SABOR)”, a multisite study
The goal of this program is to develop biomarkers based on blood, urine, and tissue using clinical values or, at UCI, molecular values that predict the upgrading of Gleason Scores of 3+3 or less as observed in diagnostic biopsies of prostate cancer patients to Gleason Scores of 3+4 or greater as observed in surgical prostatectomy tissue. Such upgrade predictors would, for example, overcome the under sampling believed to cause the deficient score from biopsy tissue and would be important in considering active surveillance regimens.
Role: UCI site-PI.
Completed, U01CA152738 (MERCOLA, DAN) Sep 1, 2010 - Jun 30, 2016
The Prostate Cancer Tumor Microenvironment Exhibits Differentially Expressed Gene
Role: Principal Investigator
U01CA114810 (MERCOLA, DAN) Sep 30, 2005 - Jun 30, 2011
Evaluation of Predictive Signatures of Prostate Cancer
Role: Principal Investigator
R01CA084107 (MERCOLA, DAN) Jul 31, 2000 - Jun 30, 2005
ONCOGENIC ROLE OF JUN KINASE IN HUMAN PROSTATE CANCER
Role: Principal Investigator
U01CA084998 (MERCOLA, DAN) Sep 30, 1999 - Mar 31, 2005
CHARACTERIZATION OF EARLY STAGE PROSTATE CANCER
Role: Principal Investigator
Collage of American Pathologists, fellow
American Urology Association
American Association for the Advancement of Scieince
American Association for Cancer Research
Dept. Veterans Affairs, San Diego 1986—1997
Assit. Clin. Prof., Pathology
Sidney Kimmel Cancer Center 1992—2005
Oxford University 1969—1973
Chemical Crystallography, Oxford Univierstiy 1970—1074
Member of the Faculty of Zoology and Principle Scientific Officer,
Oxford University, Department of Zoology, Agricultural Research Council of the U.K. 1974—1980