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Division of Genitourinary Pathology


Email jepstein@jhmi.edu
Phone (410) 955-5043

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Division of Surgical Pathology


Jonathan I. Epstein, M.D.

Director, Division of Genitourinary Pathology
Director, Division of Surgical Pathology
Primary Appointment in Pathology; Secondary Appointments in Oncology and Urology


Carcinoma of the prostate can vary from extremely indolent lesions such as those found incidentally at autopsy to aggressive tumors responsible for the second leading cause of cancer death in men. We have the largest number of completely studied radical prostatectomy specimens in the world and the largest anatomic pathology consult service of genitourinary specimens (>60/day). We are involved in multiple clinico-pathologic studies using a wide range of techniques on both biopsy and prostatectomy specimens to enhance our prognostic capabilities. Tissue microarrays are available for bladder and prostate cancer projects. The consult material also provides the unique opportunity to identify and describe new entities in genitourinary pathology.

Publications
Epstein JI, Walsh PC, CarMichael M, Brendler CB. Pathological and clinical findings to predict tumor extent of non-palpable (stage T1c) prostate cancer JAMA 271:368-374, 1994. Epstein JI, Allsbrook Jr. WC, Amin MB, Egevad LL & The ISUP grading committee. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 29: 1228-42, 2005.

Epstein JI, Amin MB, Reuter VR, Mostofi FK, and the Bladder Consensus Conference Committee. The World Health Organization/International Society of Urological Pathology Consensus Classification of Urothelial (Transitional Cell) Neoplasms of the Urinary Bladder. Am J Surg Pathol 22:1435-1448, 1998.

Pan C-C, Potter SR, Partin AW, Epstein, JI. The prognostic significance of tertiary Gleason patterns of higher grade in radical prostatectomy specimens: a proposal to modify the Gleason grading system Am J Surg Pathol 24:563-569, 2000.

Duffield A, Epstein JI. Detection of cancer in radical prostatectomy specimens with no residual carcinoma in the initial specimen. Am J Surg Pathol (January) 33:120-125,2009.




Email ljarend@jhu.edu
Phone (443) 287-0166
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Lois J. Arend, M.D., Ph.D.

Primary Appointment in Pathology


My laboratory studies the mechanisms of mammalian kidney development. Specifically, our studies involve various cell and molecular biology techniques to determine the role of the bioactive sphingolipid, sphingosine-1-phosphate (S1P), in organogenesis of the kidney. Our research indicates that S1P may be involved in development of conditions such as cystic kidney disease and Meckel syndrome. We also study the pathologic aspects of other kidney disease by various morphologic techniques, including light, immunofluorescence, and electron microscopy.

Publications
Arend LJ, Smart AM, and JP Briggs. Metanephric rat-mouse chimeras to study cell lineage of the nephron. Developmental Genetics 24(3/4):230-240, 1999

Arend LJ, Smart A, and JP Briggs. Mouse beta 6 integrin sequence, pattern of expression, and role in kidney development. J Am Soc Nephrol 11:2297-2305, 2000

Phillips CL, Arend LJ, Filson A, Kojetin D, Clendenon J, Fang S, and KW Dunn. Three dimensional imaging of embryonic mouse kidney by two-photon microscopy. Am J Pathol 158(1):49-55, 2001

Fu J, Jin Y, and LJ Arend. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of XIAP. J Biol Chem Dec 26;278(52):52660-72, 2003

Lorenz, JN, L.J. Arend, R Robitz, RJ Paul, AJ MacLennan. Vascular dysfunction in S1P2 sphingosine-1-phosphate receptor knockout mice. American Journal of Physiology- Regulatory, Integrative and Comparative Physiol 292(1):R440-6, 2007

Kirby RJ, Jin Y, Fu J, Cubillos J, Swertfeger, D, Arend LJ. Dynamic regulation of sphingosine-1-phosphate homeostasis is critical for branching morphogenesis of the mouse metanephric kidney. Am J Physiol Renal Physiol 296:F634-F641, 2009

Kirby RJ, Swertfeger, D, Arend LJ. Crosstalk between GDNF/RET and S1P/S1PR signaling pathways regulates kidney epithelial cell migration. In Preparation.




Email sbagnas1@jhmi.edu
Phone (410) 502-0812
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Serena M. Bagnasco, M.D.

Primary Appointment in Pathology


My research interests are in the field of renal physiology and pathophysiology, and in the mechanisms of adaptation of renal cells to the environment of the kidney medulla, characterized by high concentration of salt and urea. We have defined the genomic organization of the gene that encodes the major renal urea transporters, which are essential for the process of urine concentration in the mammalian kidney. We are currently studying the pathways regulating expression and function of these transporters in the kidney and at extrarenal sites.



Publications

Nakayama, Y., T. Peng, J.M. Sands, S.M. Bagnasco. The TonE/TonEBP pathway mediates tonicity-responsive regulation of UT-A urea transporter expression. Journal of Biological Chemistry, 275: 38275-38280, 2000.

Bagnasco, S.M., Tao Peng, M.G. Janech, A. Karakashian, J.M. Sands. Cloning and characterization of the human urea transporter UT-A1, and mapping of the human Slc14a2 gene. American Journal of Physiology- Renal, 281: F400-406, 2001.

Peng, T., J.M.Sands, S.M. Bagnasco. Glucocorticoids inhibit transcription and expression of the UT-A urea transporter gene. American Journal of Physiology- Renal, 282:F859-F865, 2002.

Bagnasco, S.M.. Gene structure of urea transporters. American Journal of Physiology- Renal Physiology, F3-F10, 2003.

Inoue, H., Jackson, S.D., Vikulina,T., Klein, J.D., Tomita, K., Bagnasco, S.M.. Identification and characterization of a Kidd antigen/UT-B urea transporter expressed in human colon. American Journal of Physiology-Cell Physiology, 287:C30-C35, 2004.




Email ncarte13@jhmi.edu
Phone (410) 955-2386
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Naima Carter-Monroe, M.D.

Primary Appointment in Pathology


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Publications
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Email ademarz@jhmi.edu
Phone (410) 614-5686

Related Websites
DeMarzo Laboratory

Tissue Microarray Core

Brady Urological Institute

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Angelo M. DeMarzo, M.D., Ph.D.

Primary Appointment in Pathology; Secondary Appointments in Oncology and Urology Member; Graduate Program in Pathobiology


Our basic research is focused on understanding the paradoxical organ selectivity of cancer. Specifically, why is the prostate so commonly targeted for cancer formation?

We have 4 main areas of overlapping interest.

  1. We study gene expression alterations involved in the molecular regulation of the growth of the normal prostate and how this regulation is altered in neoplastic and pre-neoplastic states.

  2. The role of inflammation, atrophy and dietary factors in prostate carcinogenesis.

  3. The role of telomere shortening as a potential mechanism for the generation of genetic instability.

  4. Using tissue microarrays we examine the clinical significance of various biomarkers in prostate cancer.
We make extensive use of immunohistochemistry, immunofluorescence, and in situ hybridization. We also employ laser capture microdissection for molecular analysis of individual tissue and cell types. We collaborate closely with several others in the Brady Urological Research Institute and The Oncology Center.

Publications

Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG, and DeMarzo 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.,163:923-933, 2003.

Nelson, W.G., De Marzo, A.M., and Isaacs, W.B. Mechanisms of disease. The molecular pathogenesis of prostate cancer: a new role for inflammation? New Eng. J. Med., 349:366-81, 2003.

Meeker, A.K., Hicks, J.L., Platz, E.A., March, G.E., Bennett, C.J.,Delannoy, M.J., De Marzo, A.M. Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Res., 62:6405-9, 2002.

De Marzo, A.M., Nelson, W.G., Isaacs, W.B., and Epstein, J.I. Pathological and molecular aspects of prostate cancer. Lancet, 361:955-64, 2003.

Meeker, A.K., Hicks, J.L., Iacobuzio-Donahue, C.A., Montgomery, E.A., Westra, W.H., Chan, T.Y., Ronnett, B.M., and De Marzo, A.M. Telomere length abnormalities occur early in the initiation of epithelial carcinogenesis. Clin Cancer Res., 10:3317-26. 2004




Email cheaphy@jhmi.edu
Phone (443) 287-4730
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Christopher M. Heaphy, Ph.D.

Primary Appointment in Pathology


The overall research goal of my laboratory is to further understand the contribution of telomere biology in cancer development and progression. For a variety of human cancers (eg. prostate, breast, ovarian, brain, pancreas), new molecular biomarkers are urgently needed for improving risk assessment and for accurate prognostication of the disease to improve upon current prevention and treatment strategies. One molecular marker that may address these clinical problems is tissue-based telomere length measurements. Telomeres are nucleoprotein complexes that function to protect and stabilize the chromosomal ends by preventing chromosome fusions, masking inappropriate double strand DNA break damage signals, and inhibiting exonucleolytic degradation. In addition to assessing the translational potential of telomere length measurements, my laboratory also is working to elucidate the underlying mechanisms of tumor initiation and progression (e.g through telomere length alterations), as well as understanding how the interactions between the tumor and its' tissue microenvironment may facilitate this process.

Publications
Heaphy CM, de Wilde RF, Jiao Y, Klein AP, Edil BH, Shi C, Bettegowda C, Rodriguez FJ, Eberhart CG, Hebbar S, Offerhaus GJ, McLendon R, Rasheed BA, He Y, Yan H, Bigner DD, Oba-Shinjo SM, Nagahashi Marie SK, Riggins GJ, Kinzler KW, Vogelstein B, Hruban RH, Maitra A, Papadopoulos N, Meeker AK. Altered telomeres in tumors with ATRX and DAXX mutations. Science, 333:425, 2011.

Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih IM, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu T, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK. Prevalence of the Alternative Lengthening of Telomeres (ALT) telomere maintenance mechanism in human cancer subtypes. The American Journal of Pathology, 179:1608-1615, 2011.

Heaphy CM, Subhawong AP, Gross A, Konishi Y, Kouprina N, Argani P, Visvanathan K, Meeker AK. Shorter telomeres in luminal B, HER-2 and triple-negative breast cancer subtypes. Modern Pathology, 24:194-200, 2011.

Heaphy CM, Schreck KC, Raabe E, Mao X, Chu Q, An P, Poh W, Jiao Y, Rodriguez FJ, Odia Y, Meeker AK, Eberhart CG. A glioblastoma neurosphere line with alternative lengthening of telomeres. Acta Neuropathologica, 126:607-8, 2013.

Heaphy CM, Yoon GS, Peskoe SB, Joshu CE, Lee TK, Giovannucci E, Mucci LA, Kenfield SA, Stampfer MJ, Hicks JL, De Marzo AM, Platz EA, Meeker AK. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discovery, 3:1130-41, 2013.




Email tlotan1@jhmi.edu
Phone (410) 434-1003

Related Websites
Institute for Basic Biomedical Sciences

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Tamara Lotan, M.D.

Primary Appointment in Pathology; Secondary Appointment in Oncology


I am a urologic pathologist with a research laboratory focused on the role of PTEN/PI3K/mTOR signaling in epithelial development and tumorigenesis. My basic science lab works with a number of epithelial systems (prostate, breast, skin) and we are principally interested in understanding how these oncogenic signaling pathways regulate epithelial differentiation, apico-basal polarity and cell migration. Using transgenic mouse models combined with 3D culture and state-of-the-art live cell imaging techniques, our hope is that by understanding the role of this signal transduction network in epithelial embryonic development, we can help to elucidate the significance of these oncogenic signals during tumorigenesis and tumor progression.

The more translational arm of my laboratory effort is focused on validating PTEN as a potential predictive and prognostic biomarker in prostate cancer, and on defining alternative mechanisms of PTEN inactivation in prostate cancer. We also have an ongoing interest in the molecular phenotype of rare subtypes of prostate cancer, including small cell carcinoma, p63-positive prostatic carcinoma and intraductal prostatic carcinoma.

Publications

Lotan TL, Wang W,Gupta NS, Toubaji A, Haffner MC, Meeker AK, De Marzo AM, Epstein JI, and Netto GJ. ERG Gene Rearrangements are Common in Prostatic Small Cell Carcinoma. Modern Pathology. 2011; 24(6):820-8.

Lotan TL, Gurel B, Sutcliffe S, Esopi D, Liu W, Xu J, Hicks JL, Park BH, Humphreys E, Partin AW, Han M, Netto GJ, Isaacs WB, De Marzo AM. PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients. Clinical Cancer Research. 2011; 17(20):6563-73.

Ghosh S, Lau H, Simons BW, Powell JD, Meyers DJ, De Marzo AM, Berman DM, Lotan TL. PI3K/mTOR Signaling Regulates Prostatic Branching Morphogenesis. Developmental Biology. 2011; 360(2):329-42.




Email ameeker@mail.jhmi.edu
Phone (410) 502-3398
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Alan K. Meeker, Ph.D.

Primary Appointment in Pathology; Secondary Appointment in Urology


Telomere Shortening in Cancer

The genesis and progression of cancer is thought to depend upon genetic instability. This is clearly seen at the chromosomal level in epithelial cancers, such as prostate and breast cancers, which show chromosomal instability as reflected by aberrations in both chromosomal number and structure, yet the molecular mechanisms responsible for chromosome destabilization during carcinogenesis and progression are largely unknown. Our lab is examining defective telomeres which appear to be an important route to chromosomal instability. Telomeres are specialized chromosomal structures consisting of terminal DNA tracts and associated binding proteins. Telomeres protect chromosome ends from fusing with other chromosome ends or other chromosomes containing DNA double strand breaks. In the absence of the telomere synthetic enzyme telomerase, telomeric DNA is subject to loss during cell division. Results from telomerase knockout mouse models indicate that telomere shortening can lead to an increased incidence of cancer in these animals, thus apparently playing a role in cancer initiation.

In close collaboration with Angelo De Marzo’s lab in the John Hopkins Pathology Department, we developed a novel quantitative fluorescence microscopy technique to measure telomere lengths directly in archival tissues, in order to find out if telomere shortening is playing a role in the initiation of human cancers. Making use of this technique in collaborative efforts with other faculty members in the Johns Hopkins Department of Pathology (Drs. Pedram Argani, Theresa Chan, Christine Iacobuzio-Donahue, Elizabeth Montgomery, Bridgette Ronnett and William Westra) we found that, indeed, telomeres are abnormally short in the vast majority of microscopic cancer precursor lesions in common epithelial cancers, including those of the bladder, breast, cervix, colon, esophagus, gall bladder, oral cavity and prostate.

Telomere length abnormalities appear to be one of the earliest and most prevalent molecular genetic alterations acquired in the multi-step process of tumorigenesis. These findings support a model whereby telomere dysfunction induces a mutator phenotype that acts at the chromosomal and sub-chromosomal levels to accelerate tumor development. We hypothesize that pre-malignant lesions displaying short telomeres are poised on the edge of genetic instability, and are therefore at risk of progressing on to fully invasive carcinomas.

Practically speaking, telomere shortening may have utility in cancer diagnosis, as well as an intermediate endpoint marker in chemoprevention studies. In addition, if telomere shortening is indeed playing a causal role in cancer initiation, then it represents a valid prevention target in its own right.

Telomere Shortening in Aging

Cells normally respond to short telomeres by halting their cell division activities or by committing cellular suicide (apoptosis). It is thought that these responses evolved in long-lived multicellular organisms to prevent the outgrowth of potentially cancerous cell populations. It has been postulated that a loss of division potential due to telomere shortening in proliferating tissues might contribute to certain age-related pathologies, such as the decreased wound healing seen in the elderly. This theory has been difficult to evaluate, as previous methods of telomere length measurement only gave information on the average telomere length of a large number of cells combined.

We believe that our telomere length assay, which features single cell resolution, can be used to test the hypothesized link between telomere shortening and human aging.

Publications

Meeker, A.K., Gage, W.R., Simon, I., Coffman, J.R., Platz, E.A., March, G., and DeMarzo, A.M. Telomere Length Assessment in Human Archival Tissues: Combined Telomere Fluorescent in Situ Hybridization and Immunostaining. American Journal of Pathology. 160:1259-1268, 2002.

Meeker, A.K., Hicks, J.L., Platz, E.A., March, G.E., Bennett, C.J., and De Marzo, A.M. Telomere Shortening is an Early Somatic DNA Alteration in Human Prostate Tumorigenesis. Cancer Research. 62:6405-6409, 2002.

Montgomery, E.A., Argani, P., Hicks, J.L., DeMarzo, A.M., and Meeker, A.K. Telomere Lengths of Translocation Associated and Non-Translocation Associated Sarcomas Differ Dramatically. American Journal of Pathology. 164:1523-1529, 2004.

Meeker, A.K., Hicks, J.L., Iacobuzio-Donahue, C.A., Montgomery, E.A., Westra, W.H., Chan, T.Y., Ronnett, B.M., and DeMarzo, A.M. Telomere Length Abnormalities Occur Early in the Initiation of Epithelial Carcinogenesis. Clinical Cancer Research. 10:3317-3326, 2004.

Meeker, A.K., Hicks, J.L., Gabrielson, E., Strauss, W.M., De Marzo, A.M., and Argani, P. Telomere Shortening Occurs in Subsets of Normal Breast Epithelium as well as In Situ and Invasive Carcinoma. American Journal of Pathology. 164:925-935, 2004.




Email hmiyamo1@jhmi.edu
Phone (410) 614-1442
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Hiroshi Miyamoto, M.D., Ph.D.

Primary Appointment in Pathology; Secondary Appointment in Urology


My research interests include molecular biology of steroid hormone receptors in genitourinary tumors. Specifically, we have been investigating the role of androgen receptor signals in the development and progression of bladder cancer. Epidemiological and clinical data indicate that men have a substantially higher risk of bladder cancer, whereas women tend to present with more aggressive tumors. The underlying mechanisms of how androgens regulate bladder tumorigenesis and tumor outgrowth will offer explanations for these gender-specific differences in cancer incidence and aggressiveness. We also assess the effects of new classes of androgen receptor antagonists on prostate cancer progression and characterize novel androgen receptor coregulators in prostate cancer cells.

Publications
Miyamoto H, Yang Z, Chen Y-T, Ishiguro H, Uemura H, Kubota Y, et al. Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst 99: 558-68, 2007.

Miyamoto H, Zheng Y, Izumi K. Nuclear hormone receptor signals as new therapeutic targets for urothelial carcinoma. Curr Cancer Drug Tar 12: 14-22, 2012.

Zheng Y, Izumi K, Li Y, Ishiguro H, Miyamoto H. Contrary regulation of bladder cancer cell proliferation and invasion by dexamethasone-mediated glucocorticoid receptor signals. Mol Cancer Ther 11: 2621-32, 2012.

Izumi K, Zheng Y, Hsu J-W, Chang C, Miyamoto H. Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: A potential mechanism of androgen-induced bladder carcinogenesis. Mol Carcinogen 52: 94-102, 2013.

Li Y, Zheng Y, Izumi K, Ishiguro H, Ye B, Li F, Miyamoto H. Androgen activates ß-catenin signaling in bladder cancer cells. Endocr-Relat Cancer 20: 293-304, 2013.




Email gnetto1@jhmi.edu
Phone (410) 955-5082
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Georges J. Netto, M.D.

Primary Appointment in Pathology; Secondary Appointment in Urology


Current research is focused on the evaluation of molecular biomarkers that can serve as potential prognosticators and or therapeutic targets in the management of urologic malignancies. These studies are facilitated by the construction of Tissue Micro Arrays coupled with Image Analysis technology to be used for immunohistochemistry and FISH analysis of prostatic, bladder, renal and testicular cancers. Molecular Diagnostic applications with potential role in screening and early detection of urologic malignancies are also investigated.

Ongoing prostate cancer studies include the evaluation of the role of TMPRSS2-ERG translocation, proliferation markers (MCM2 and Ki67) and members of the mTOR pathway in predicting progression of prostate cancer in a large well characterized nested case-control cohort of prostate carcinoma patients. The studies are funded by several grants awarded from the Koch Prostate Cancer Foundation and the Patrick C Walsh Foundation in addition to the NIH/NCI sponsored Johns Hopkins Prostate SPORE.

Studies on urothelial carcinoma involve evaluation of biomarkers in a newly constructed tissue array from a well characterized cohort of cystectomy patients treated at the Brady Institute of Urology. Markers under study include: cell cycle control elements, EGFR expression and mutation analysis, PIK3CA mutation analysis and DNA damage response elements and mTOR pathway members. These studies are supported by the 2008 FAMRI Clinical Innovator Award, Johns Hopkins Philanthropic Bladder Fund and NIH/NCI sponsored grants including a PO1 program award.

Studies on renal cell carcinoma involve evaluation of mTOR, anf HIF1a/VEGFpathways in a newly constructed tissue array from a well characterized partial and radical nephrectomy cohort of clear cell, papillary and chromphobe renal carcinoma patients treated at the Brady Institute of Urology. Investigation of biomarkers of potential diagnostic and targets of therapy in rarer types of renal tumors (medullary carcinoma and collecting duct carcinoma).

Testicular tumors research studies include the evaluation of telomere status , global and promoter methylation in Germ cell tumors of testis.

Publications

D'Antonio KB, Toubaji A, Albadine R, Mondul AM, Platz EA, Netto GJ, Getzenberg RH. Extracellular Matrix Associated Protein CYR61 is Linked to Prostate Cancer Development. J Urol. 2010 Feb 19. [Epub ahead of print] PubMed PMID: 20172544.

Miyamoto H, Miller JS, Fajardo DA, Lee TK, Netto GJ, Epstein JI. Non-invasive papillary urothelial neoplasms: the 2004 WHO/ISUP classification system. Pathol Int. 2010 Jan;60(1):1-8. PubMed PMID: 20055945.

Schaeffer EM, Guzzo TJ, Furge KA, Netto G, Westphal M, Dykema K, Yang X, Zhou M, The BT, Pavlovich CP. Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy. BJU Int. . [Epub ahead of print] PubMed PMID: 20002663..

Leman ES, Magheli A, Yong KM, Netto G, Hinz S, Getzenberg RH. Identification of nuclear structural protein alterations associated with seminomas. J Cell Biochem. 2009 Dec 15;108(6):1274-9.

Albadine R, Latour M, Toubaji A, Haffner M, Isaacs WB, A Platz E, Meeker AK, Demarzo AM, Epstein JI, Netto GJ. TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma. Mod Pathol. 2009 Nov;22(11):1415-22.

Verheul HM, van Erp K, Homs MY, Yoon GS, van Der Groep P, Rogers C, Hansel DE, Netto GJ, Pili R. The Relationship of Vascular Endothelial Growth Factor and Coagulation Factor (Fibrin and Fibrinogen) Expression in Clear Cell Renal Cell Carcinoma. Urology. 2009 Aug 14.




Email ksfanos@jhmi.edu
Phone (443) 287-4592

Related Websites
DeMarzo Laboratory

The Sfanos Lab

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Karen S. Sfanos, Ph.D.

Primary Appointment in Pathology


The Sfanos lab focuses on the study of human prostate cancer, with a particular emphasis on cancer prevention strategies as well as the etiological factors which may contribute to prostate cancer initiation and/or progression. We are specifically interested in agents that may lead to chronic prostatic inflammation, such as bacterial infections and prostatic concretions called corpora amylacea. Our work is based on the hypothesis that inflammation plays a key role in the development of the proposed “risk factor lesions” to human prostate cancer, i.e., proliferative inflammatory atrophy (PIA) and high grade prostatic intraepithelial neoplasia (PIN). Our previous studies have demonstrated the presence of multiple microbial species in the prostate of cancer patients and, importantly, many of the organisms identified are consistent with genera associated with inflammation-associated conditions including bacterial prostatitis and/or urinary tract infections. Dr. Sfanos works very closely with both genitourinary pathologists as well as epidemiologists in an effort to correlate discoveries in the laboratory with prostate cancer risk as well as disease pathology.

Publications

Sfanos K.S., Sauvageot J., Fedor H.L., Dick J.D., De Marzo A.M., Isaacs W.B. A molecular analysis of prokaryotic and viral DNA sequences in prostate tissue from patients with prostate cancer indicates the presence of multiple and diverse microorganisms. The Prostate, 68(3):306-320, 2008.

Sfanos K.S., Bruno T.C., Maris C.H., Xu L., Thoburn C.J., De Marzo A.M., Meeker A.K., Isaacs W.B., Drake C.G. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clinical Cancer Research, 14:3254-3261, 2008.

Sfanos K.S., Wilson B.A., De Marzo A.M., Isaacs W.B. Acute inflammatory proteins constitute the organic matrix of prostatic corpora amylacea and calculi in men with prostate cancer. Proceedings of the National Academy of Sciences (PNAS) U.S.A., 106:3443-3448, 2009.

Sfanos K.S., Bruno T.C., Meeker A.K., De Marzo A.M., Isaacs W.B., Drake C.G. Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. The Prostate, 69(15):1694-1703, 2009.

Aloia A.L.*, Sfanos K.S.*, Isaacs W.B., Zheng Q., Maldarelli F., De Marzo A.M., Rein A. XMRV: A new virus in prostate cancer? Cancer Research, 70:10028-10033, 2010.

Sfanos, K.S., Aloia, A.L., Hicks, J.L., Esopi, D.M., Steranka, J.P., Shao, W., Sanchez-Martinez, S., Yegnasubramanian, S., Burns, K.H., Rein, A., De Marzo, A.M. Identification of replication competent murine gammaretroviruses in commonly used prostate cancer cell lines. PLoS ONE, 6(6): e20874, 2011.

Sfanos, K.S., Aloia, A.L., De Marzo, A.M., Rein, A. XMRV and prostate cancer: A “final” perspective. Nature Reviews Urology, 9(2):111-118, 2012.

Mak T.N., Yu, S.H., De Marzo, A.M., Brüggemann H., Sfanos K.S. Multilocus Sequence Typing (MLST) Analysis of Propionibacterium acnes Isolates from Radical Prostatectomy Specimens. The Prostate 2012, In Press.



 


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