Phs 398/2590 (rev. 06/09), biographical sketch format page

Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.
Professor of Pathology, Urology and Oncology eRA COMMONS USER NAME (credential, e.g., agency login) ADEMARZ1 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)
A. Personal Statement
Our laboratory is extensively involved in tissue banking in the prostate cancer research program at Johns
Hopkins, and I am director of the Pathology Core for our prostate SPORE. I am a trained surgical pathologist
with clinical expertise and more than 10 years of experience in prostate pathology. Our laboratory focuses on
the study of prostate cancer, paying special attention to disease etiology and prevention. We have postulated
that inflammation and dietary practices result in injury to prostate epithelial cells. This injury results in DNA
damage, cell death, regeneration, CpG island gene methylation, mutation and ultimately the formation of
prostatic intraepithelial neoplasia (PIN), a neoplastic lesion that can lead to invasive prostate cancer. The
laboratory is also interested in determination of the molecular and cellular mechanisms of neoplastic
transformation in the prostate. For example, using human tissue specimens, genetically engineered mouse
models, and cell culture systems, our group is studying the role of the MYC oncogene, and a number of its
downstream target genes, in prostate cancer cell neoplastic transformation and cell growth regulation. Since
MYC is a key regulator of stem cells, these studies have direct implications for stem cell models of prostate
cancer formation. The laboratory also has a number of ongoing translational research efforts. One such
program focuses on biomarker development, where our group has been leading efforts to apply novel
biomarkers to human prostate tissues, where such biomarkers might aid the pathologist in making a diagnosis
on challenging biopsy cases. As director of the tissue microarray core at Johns Hopkins, I have also been
involved in tissue microarray technology including the development of an open source tissue microarray
software and database system (TMAJ), implemented at a number of institutions.
B. Positions and Honors
Positions and Employment
Intern, Dept. of Pathology, The Johns Hopkins University School of Medicine Resident, Dept. of Pathology, The Johns Hopkins University School of Medicine Chief Resident, Dept. of Pathology, The Johns Hopkins University School of Medicine Research Fellow, Depts. of Urology and Pathology, The Johns Hopkins University School of Medicine Instructor, Dept. of Pathology, The Johns Hopkins University School of Medicine Assistant Professor, Pathology, Urology, and Oncology, The Johns Hopkins University School of Medicine Director, Johns Hopkins Tissue Microarray Laboratory Associate Professor of Pathology, Urology, and Oncology, The Johns Hopkins University School of Medicine Associate Director for Pathology Cancer Research, The Sidney Kimmel Comprehensive Cancer Center Professor of Pathology, Urology, and Oncology. The Johns Hopkins University School of Medicine Other Experience and Professional Memberships
Ad Hoc Reviewer: U01 Application – NIH/NCI Ad Hoc Reviewer: Special Emphasis Panel R21 Application – NIH/NCI Study Section Initial Review Group Member: Bioengineering Sciences and Technology IRG, Center for Scientific NIH Integration Panel Committee Member – Department of Defense, Congressionally Directed Medical Research Prostate Cancer Research Program Member of Special Emphasis Panel/Scientific Review Group, the Specialized Program of Research Excellence (SPORE), National Cancer Institute Ad Hoc Reviewer: Chemo/Dietary Prevention Study Section [CDP], R01 and R21 grants Prostate Cancer Foundation Challenge Awards Standing Peer Review Committee, 4/2008 Study Section Member ARRA RC1 Challenge Grant applications. Mail reviewer for ZRG1 OTC-K (58) in the Oncology-2 Translational Clinical IRG (OTC) Member of Special Emphasis Panel/Scientific Review Group, the Specialized Program of Research Excellence (SPORE), National Cancer Institute, SPORE in Brain, Prostate, Kidney, Breast Cancers and Melanoma Editorial Board Member on The Prostate, Cancer Prevention Research Honors
Stowell-Orbison Award for Research by a Pathologist-In-Training, International Academy of Pathology Harvey/Burrough’s Wellcome Clinician Scientist Award, The Johns Hopkins School of Medicine Mentored Clinician Scientist Award (K08), National Cancer Institute Donald S. Coffey Prostate Cancer Foundation Physician/Scientist Award
C. Selected Peer-reviewed Publications
Most relevant to the current application
1. Nelson WG, De Marzo AM, and Isaacs WB. Mechanisms of disease. The Molecular Pathogenesis of
Prostate Cancer: a New Role for Inflammati 2. Van Leenders, GJ, Gage, WR, Hicks JL, Van Balken, B, Aalders, TW, Schalken, JA, and De Marzo AM. Intermediate Cells in Human Prostate Epithelium are Enriched in Proliferative inflammatory Atrophy. Am J Pathol, 2003; 162:1529-37. 3. De Marzo AM, Nelson WG, Isaacs WB, and Epstein JI. Pathological and Molecular Aspects of Prostate 4. Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG, and De Marzo AM. Hypermethylation of the Human Glutathione S-transferase-pi Gene (GSTP1) CpG Island is Present in a subset of Proliferative Inflammatory Atrophy Lesions But Not in Normal or Hyperplastic Epithelium of the Prostate: A Detailed Study Using Laser-Capture Microdissection. Am J Pathol., 2003; 163:923-933. 5. Bethel CR, Faith D, Li X, Guan B, Hicks JL, Lan F, Jenkins RB, Bieberich CJ, and De Marzo AM. Decreased NKX3.1 Protein Expression in Focal Prostatic Atrophy, Prostatic Intraepithelial Neoplasia and Adenocarcinoma: Association with Gleason Score and Chromosome 8p Deletion. Cancer Res. 2006; 66:10683-90. 6. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG. Inflammation in Prostate Carcinogenesis. Nat Rev Cancer. 2007; 7:256-69. 7. Gurel B, Iwata T, Koh C, Jenkins RB, Lan F, Dang CV, Hicks JL, Morgan J, Cornish TC, Sutcliff S, Isaacs WB, Luo J, De Marzo AM. Nuclear MYC Protein Overexpression Is an Early Alteration in Human Prostate Carcinogenesis. Modern Path. 2008; 21:1156-1167. PMC Journal - In Process. 8. Yegnasubramanian S, Haffner MC, Zhang Y, Gurel B, Cornish TC, Wu Z, Irizarry RA, Morgan J, Hicks J, DeWeese TL, Isaacs WB, Bova GS, De Marzo AM, Nelson WG. DNA Hypomethylation Arises Later in Prostate Cancer Progression Than CpG Island Hypermethylation and Contributes to Metastatic Tumor Heterogeneity. Cancer Res, 2008; 68:8954-8967. PMCID2577392. 9. Dunn TA, Fedor H, Isaacs WB, De Marzo, AM, Luo J. Genome-Wide Expression Analysis of Recently Processed Formalin-Fixed Paraffin Embedded Human Prostate Tissues. Prostate, 2009 Oct 30; 69:214-8. PMCID2612089. 10. Parsons JK, Saria EA, Nakayama M, Vessella RL, Sawyers CL, Isaacs WB, Faith DA, Bova GS, Samathanam CA, Mitchell R, De Marzo AM. Comprehensive Mutational Analysis and mRNA Isoform Quantification of TP63 in Normal and Neoplastic Human Prostate Cells. Prostate 2009; 69:559-69. PMCID2875878. 11. Hill KM, Kalifa S, Das JR, Bhatti T, Gay M, Williams D, Taliferro-Smith L, De Marzo AM. The Role of PI 3- Kinase p110 Beta in AKT Signally, Cell Survival, and Proliferation in Human Prostate Cancer Cells. Prostate. 2010 Jan 7 [Epub ahead of print]. NIHMS179040. 12. Haffner MC, Aryee MJ, Toubaji A, Esopi DM, Albadine R, Gurel B, Isaacs WB, Bova GS, Liu W, Xu J, Meeker AK, Netto G, De Marzo AM, Nelson WG, Yegnasubramanian S. Androgen-induced TOP2B-Mediated Double-Strand Breaks and Prostate Cancer Gene Rearrangements. Nat Genet. 2010; 42:647-8. PMC Journal - In Process. Additional recent publications of importance to the field (in chronological order)
1. Meeker AK, Hicks JL, Iacobuzio-Donahue CA, Montgomery EA, Westra WH, Chan TY, Ronnett BM, De
Marzo AM. Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis. Clin Cancer Res. 2004; 10: 3317-26. 2. c-Myc Suppression of miR-23a/b Enhances Mitochondrial Glutaminase Expression and Glutamine Metabolism. Gao P, Tchernyshyov I, Chang TC, Lee YS, Kita K, Ochi T, Zeller KI, De Marzo AM, Van Eyk JE, Mendell JT, Dang CV. Nature. 2009; 458:762-5. PMCID2729443. 3. Sfanos KS, Wilson BA, De Marzo AM, Isaacs WB. Acute Inflammatory Proteins Constitute the Organic Matrix of Prostatic Corpora Amylacea and Calculi in Men with Prostate Cancer. Proc Natl Acad Sci U S A, 2009; 106:3443-8. PMCID2651291.
D. Research Support
Ongoing Research Projects
2P50CA103175-06A2 (Bhujwalla)
NCI JHU ICMIC Program This center grant funds an in vivo Cellular and Molecular Imaging Center at Johns Hopkins. The program consists of four research components, four developmental projects, one career development award and four resources. P50 CA58236 (Nelson) NCI SPORE in Prostate Cancer Core 2 – Tissue Archive Core The major goals of this project are to provide a core facility for pathology for the Prostate SPORE. This involves a tissue repository, tissue microarray production, pathology diagnostics, immunohistochemistry, and DNA microarray facilities. P50DK082998-01A109 (Getzenberg) Novel Translational Approaches to BPH/LUTS Project 1 (Platz) Benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) represents one of the most
common diseases occurring in aging men in the United States. These are complex diseases that require
molecular classification and novel therapeutic approaches. To address these needs, we have prepared this
application for a George M. O’Brien Urology Center which is focused on BPH/LUTS. The Center consists of
four projects, each of which is translational / clinical in nature. This O’Brien Center should provide new insights
and approaches to these common issues that affect almost all men as they age. The goal of Project 1 is to
test whether intraprostatic inflammation and focal atrophy contribute to lower urinary tract symptoms (LUTS)
and their progression irrespective of concurrent transition zone hyperplasia or diagnosis of benign prostatic
hyperplasia (BPH), and to determine whether finasteride reduces the extent of intraprostatic inflammation and
focal atrophy and thus LUTS.

Completed Projects Within Last Three Years
Johns Hopkins Medical Institution (Eisenberg)
Patrick C. Walsh Prostate Cancer Research Foundation Molecular Studies in men with Prostate Cancer treated with androgen deprivation. To evaluate clinical and molecular parameters that can help identify patients that will or will not benefit from androgen deprivation. Johns Hopkins Medical Institution (De Marzo) Patrick C. Walsh Prostate Cancer Research Foundation MYC Induced Transformation of Prostate Epithelial Cells. The aim of this project is investigate mechanism by which the oncogenic transcription factor MYC transforms prostate epithelial cells. Maryland Technology Development Corp (Isaacs) Developing Methods for the Identification and Isolation of Prostate Cancer Stem Cells The major goal of this project is to accelerate rational development of effective therapies for both the prevention and treatment of prostate cancer. 5P30CA006973-469041 (Nelson) Comprehensive Cancer Center Core Grant Regional Oncology Research Center The major goals of this core are to provide a center for the creation of tissue microarrays (TMAs), and for imaging of TMA slides for Johns Hopkins and other researchers. U54 CA091409 (Nelson) NCI Howard/Hopkins Cancer Center Partnership Biospecimen Core The major aim of this grant proposal is to continue the development of a sustainable partnership between Howard University Cancer Center (HUCC) and the Sidney Kimmel comprehensive Cancer Center (SKCCC) at Johns Hopkins that enhances the research, training, education, and outreach missions of both institutions. The primary mission of this Core is to serve investigators at both institutions in their studies related to health disparities by providing high quality prostate tissue specimens obtained from both African American and Caucasians with the ultimate goals of contributing to the prevention and/or cure of prostate cancer and the understanding of the basis of the marked disparity in prostate cancer incidence and outcomes. PC050457 (De Marzo) Department of Defense Congressional Dir. Med. Research Program Interactions Between Dietary Factors and Inflammation in Prostate Carcinogenesis The major goals of this project are to determine whether there are synergistic actions between diet and infectious agents in causing chronic inflammation and cancer in the rat prostate.


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