| Laboratory Medicine and Pathobiology --- University of Toronto

Horizontal Tabs Group

Research

Our laboratory has recently cloned numerous novel genes, in particular those that belong to the kallikrein gene family.

The kallikreins are a group of related serine proteases, clustered in tandem on human chromosome 19q13.4

Our research interests related to kallikreins include the following:

1.         Kallikrein gene structure and transcriptional regulation.
2.         Kallikrein protein function and enzymology.
3.         Discovery of physiological pathways involving kallikreins (including enzymatic cascades).
4.         Identification of physiological substrates for kallikreins.
5.         Kallikrein gene rearrangements in cancer.
6.         Kallikreins as diagnostic and therapeutic targets.
7.         Kallikreins and Proteinase-Activated Receptors (PARs)

To achieve these goals we develop innovative tools for kallikrein research such as recombinant proteins, monoclonal antibodies, immunological and molecular assays and immunohistochemical procedures. Also, through our collaborators, we use fluorogenic combinatorial libraries and phage-display technology to delineate kallikrein substrates and function. More recently, we are using mass spectrometric techniques to discover novel kallikrein targets and inhibitors.

We have access to large biorepositories of biological fluids, tissues and nucleic acids, which are invaluable in our efforts to identify novel cancer biomarkers and new ways for diagnosing and monitoring human disease. An international group of investigators is working closely with us by providing valuable clinical material for translational research.

Translational Research

Some of our translational research interests include:

1.         Identification of potential clinical applications of kallikreins (diagnostic markers, therapeutic targets, predictors of prognosis and therapeutic response
2.         Involvement of kallikreins in non-malignant diseases (neurodegeneration, skin diseases, etc.)
3.         Identification of non-kallikrein biomarkers that could be used for diagnosis, therapy and monitoring of cancer and other diseases.

Cancer Therapeutics

We are using high-throughput technologies to screen candidate drug molecules from large chemical libraries. Recently, we screened libraries such as Spectrum, Prestwick and LOPAC and identified members of the cardiac glycoside family as potential anti-cancer agents. Our efforts to identify therapeutic molecules which could act either alone, or in a synergistic way, against cancer are continuing.

Male Infertility

In collaboration with Dr. Keith Jarvi from the Murrray Koffler Urologic Wellness Centre, we are delineating the proteomes of seminal plasma and associated fluids in our efforts to identify biomarkers of infertility and urological diseases such as prostate cancer. In collaboration with Dr. Alex Zlotta, we are studying genomic, proteomic and transcriptomic signatures of prostate cancer.

Pathobiology and Biomarkers of Autoimmune Diseases

In collaboration with Dr. Dafna Galdman and Dr. Vinod Chandran, Professors at the Department of Medicine, Division of Rheumatology, Center for Prognostic Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, we are conducting proteomic studies to identify novel biomarkers of autoimmune and rheumatic diseases including psoriasis, psoriatic arthritics, systemic lupus erythematosus, etc. In such studies, we also collaborate with Drs. Morley Hollenberg, University of Calgary and Dr. Martin Steinhoff, Center for the Neurobiology of Digestive Diseases, University of California, San Francisco, USA

Neurodegeneration

One research interest of the ACDC Laboratory is identification of biomarkers of early diagnosis of neurodegenerative diseases such as Alzheimer's and Parkinson's Disease. Some of our local and international collaborators on this project include Dr. Anthony Lang, Toronto Western Hospital, University Health Network and Dr. Ana-Maria Simundic, University Hospital "Sestre Milosrdnice", Zagreb, Croatia.

Professor

Dr. Diamandis currently serves as Division Head of Clinical Biochemistry at Mount Sinai Hospital and Biochemist-in-Chief at the University Health Network and is Professor & Head, Clinical Biochemistry, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. His research activities evolve around discovery and validation of cancer biomarkers, proteomics, mass spectrometry and translational research.

Dr. Diamandis received his B.Sc. in Chemistry, Ph.D. in Analytical Chemistry and M.D. from the University of Athens, Greece and a Diploma in Clinical Biochemistry from the University of Toronto, Canada. He is a Certified Clinical Chemist by the Canadian Academy of Clinical Biochemistry and the American Board of Clinical Chemistry.

Dr. Diamandis is a Member of 45 Journal Advisory Scientific and Editorial Boards, including The Journal of Biological Chemistry, Cancer Research, Molecular Cancer Research, Journal of Clinical Oncology, Clinical Chemistry and Journal of Proteome Research. He has received numerous awards from both national and international organizations. These include: American Association for Clinical Chemistry Award for Outstanding Scientific Achievements by a Young Investigator (1985); Annual Research Excellence Award of the Canadian Society of Clinical Chemists (1995); Excellence in Teaching Award, Department of Clinical Biochemistry, University of Toronto (1997); Distinguished Scientist Award, Clinical Ligand Assay Society (CLAS) (1999); American Association for Clinical Chemistry Award for Outstanding Contributions to Clinical Chemistry in a Selected Area of Research (1999); Van Slyke Award, the New York Metro Section of the American Association for Clinical Chemistry (1999); Distinguished Scientist Award, National Academy of Clinical Biochemistry (NACB) (2000); Miriam Reiner Award from the Capital Section of the American Association for Clinical Chemistry (2001); Abbott Award from the International Society for Oncodevelopmental Biology and Medicine (ISOBM) (2002); Annual Education Excellence Award of the Canadian Society of Clinical Chemists (2003); Frey-Werle Commemorative Gold Medal from the Frey-Werle Foundation (2007); The Morton K. Schwartz Award for Significant Contributions in Cancer Research Diagnostics from the American Association for Clinical Chemistry (AACC) (2007); Outstanding Contributions to Clinical Biochemistry Award from the Ontario Society of Clinical Chemists (OSCC) (2008); The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)/Abbott Award for Significant Contributions to Molecular Diagnostics (2009); Excellence in Biomedical Research Nemitsas Prize in Medical Sciences, Takis and Louki Nemitsas Foundation (2010); Senior Sustained Excellence in Graduate Teaching Award, Faulty of Medicine, University of Toronto (2013)and the Carl Joliff Award for Lifetime Achievement in Clinical and Diagnostic Immunology (2013); CCSC Award for Outstanding Contributions to Clinical Chemistry (2014); The JJ Berry Smith Award for Doctoral Supervision, University of Toronto, Canada (2014). Dr. Diamandis is highlighted for his citation record in: The Provincial Government of Ontario document entitled “Ontario’s Innovation Agenda” (2010), [www.ontario.ca/innovation; page 11]. He has more than 43,000 lifetime citation and an H-index of 105.

Other major distinctions of Dr. Diamandis include his election as Corresponding Member of the Academy of Athens, Greece (2005), Member of the Royal Society of Canada (2008). Fellow of the American Association for the Advancement of Science (2011) and Fellow of the Canadian Academy of Health of the Sciences (2012). He has published 108 review papers, 531 research papers and co-authored 4 books and 39 book chapters. He is the inventor of 28 issue and 21pending patents and supervised 20 MSc. and 28 PhD. theses.

The research interests of Dr. Diamandis are as follows:

1.         Kallikrein Biology and Pathophysiology
2.         Proteomics
3.         Tumor Markers
4.         Mechanisms of Carcinogenesis and Metastatic Progression
5.         Translational Research
6.         Cancer Therapeutics
7.         Male Infertility
8.         Pathobiology and Biomarkers of Autoimmune Diseases
9.         Neurodegeneration

Lab

Lab Website:

Diamandis Lab Website

The Advanced Center for the Detection of Cancer (ACDC Lab) is the research laboratory of Dr. Eleftherios P. Diamandis and is located in Suite m6-201, 60 Murray Street, Toronto, Ontario, Canada M5T 3L9.

Our research group consists of approximately 20 to 25 members, including about 10 to 12 Graduate Students working towards a Doctoral or Masters Degree, 3 to 5 Post-Doctoral Fellows and 4 to 5 Research Technologists. We also accommodate 2 to 4 Undergraduate Students or volunteers. Our Graduate Students and Post-Doctoral Fellows are registered with the Graduate School of the Department of Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto.

Our laboratory research interests are outlined in the “Overview” section of this web site. Briefly, our laboratory focus is on basic and translational research related to cancer and other diseases. We use genomic, molecular, proteomic, immunological and other techniques to achieve our goals, working with cells, animal models and humans. We are focusing on discovery of better ways to diagnose, monitor, and treat cancer, especially endocrine-related cancers such as those of the ovary, breast and prostate.

We offer excellent space and other facilities, advanced instrumentation, computers and everything else that is necessary for leading-edge research. We collaborate with a large number of international investigators. Our laboratory is well funded.

The Laboratory Director promotes creativity, independence and supports a collaborative environment through weekly research meetings, daily discussions and participation at national and international conferences.

The Laboratory strives to create a pleasant and collegial environment and promotes extracurricular activities, including sports, music, an annual summer barbeque and social events.

Publications

See all Publications: PubMed

Selected list of publications

Reviews

2011

Cho C-KJ, Diamandis EP. Application of proteomics to prenatal screening and diagnosis for aneuploidies. Clin Chem Lab Med 2011;49:33-41.

Saraon P, Jarvi K, Diamandis EP. Molecular alterations during progression of prostate cancer to androgen independence. Clin Chem 2011;57:1366-1375.

Bayani J, Diamandis EP. The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6). Clin Chem Lab Med 2011;50:211-233.

2012

Konvalinka A, Diamandis EP. Searching for new biomarkers of renal diseases through proteomics. Clin Chem 2012;58:353-365.

Musrap N, Diamandis EP. Revisiting the complexity of the ovarian cancer microenvironment - clinical implications for treatment strategies. Mol Cancer Res 2012;10:1254-1264.

Chung, H, Hamza M, Oikonomopoulou K, Gratio V, Saifeddine M, Virca GD, Diamandis EP, Hollenberg MD, Darmoul D. Kallikrein-related peptidase signaling in colon carcinoma cells: Targeting proteinase-activated receptors. Biol Chem 2012;393:413-420.

Rifai N, Diamandis EP, Lo YM, Kricka LJ, Wilding P, Ladenson JH, Wittwer CT. Advancing laboratory medicine through innovation: a tale of six inventors. Clin Chem 2012;58:502-510.

Leung F, Diamandis EP, Kulasingam V. From the bench to bedside: discovery of ovarian cancer biomarkers using high-throughput technologies in the past decade. Biomark Med 2012;6:613-625.

Sardana G, Diamandis EP. Biomarkers for the diagnosis of new and recurrent prostate cancer. Biomark Med 2012;6:587-596.

Karagiannis GS, Poutahidis T, Erdman SE, Kirsch R, Riddell RH, Diamandis EP. Cancer-associated fibroblasts drive the progression of metastasis through both paracrine and mechanical pressure on cancer tissue. Mol Cancer Res 2012;10:1403-1418.

2013

Pavlou M, Diamandis EP, Blasutig IM. The long journey of cancer biomarkers from the bench to the clinic. Clin Chem 2013;59:147-157.

Chan A, Diamandis EP, Blasutig I. Strategies for discovering novel pancreatic cancer biomarkers. J Proteomics 2013;81:126-134.

Oikonomopoulou K, Brinc D, Kyriacou K, Diamandis EP. Infection and cancer: Revaluation of the hygiene hypothesis. Clin Cancer Res 2013;19:2834-2841.

Cretu D, Diamandis EP, Chandran V. Delineating the synovial fluid proteome: Recent advancements and ongoing challenges in biomarker research. Crit Rev Clin Lab Sci 2013;50:51-63.

Kuzmanov U, Kosanam H, Diamandis EP. The sweet and sour of serological glycoprotein tumor biomarker quantification. BMC Med 2013;11:31.

Schmitt M, Magdolen V, Yang F, Kiechle M, Bayani J, Yousef GM, Scorilas A, Diamandis EP, Dorn J. Emerging clinical importance of the cancer biomarkers kallikrein-related peptidases (klk) in female and male reproductive organ malignancies. Radiol Oncol 2013;47:319-329

Dorn J, Bayani J, Yousef G, Yang f, Magdolen V, Kiechle M, Diamandis EP, Schmitt M. Clinical utility of kallikrein-related peptidases (KLK) in urogenital malignancies. Thromb Haemost 2013;110:408-422.

Leung F, Musrap N, Diamandis EP, Kulasingam V. Advances in mass spectrometry-based technologies to direct personalized medicine in ovarian cancer. Transl Proteomics 2013;1:74-86.

Sölétormos G, Duffy MJ, Hayes DF, Sturgeon CM, Barak V, Bossuyt PM, Diamandis EP, Gion M, Hyltoft-Petersen P, Lamerz RM, Nielsen DL, Sibley P, Tholander B, Tuxen MK, Bonfrer JM. Design of tumor biomarker-.monitoring trials: a proposal by the European Group on Tumor Markers. Clin Chem 2013;59:52-9

2014

Dorn J, Beaufort N, Schmitt M, Diamandis EP, Goettig P, Magdolen V. Function and clinical relevance of kallikrein-related peptidases and other serine proteinases in gynaecological cancers. Crit Rev Clin Lab Sci 2014;51:63-84.

Chrystoja CC, Diamandis EP. Whole genome sequencing as a diagnostic test: Challenges and opportunities. Clin Chem 2014:60;724-33.

Drabovich AP, Saraon P, Jarvi K, Diamandis EP. Seminal plasma as a diagnostic fluid for disorders of male reproductive system. Nat Rev Urol 2014:11;278-88.

Sokratous K, Hadjisavvas A, Diamandis EP, Kyriacou K. The role of ubiquitin-binding domains in human pathophysiology. Crit Rev Clin Lab Sci 2014;51:280-90.

Yu Y, Prassas I, Diamandis EP. Putative kallikrein substrates and their (patho) biological functio. Biol Chem. 2014;395:931-43

Oikonomopoulou K, Brinc D, Hadjisavvas A, Christofi G, Kyriacou K, Diamandis EP. The bifacial role of helminths in cancer: involvement of immune and non-immune mechanisms. Crit Rev Clin Lab Sci 2014;51:138-48.

Bauça JM, Martínez-Morillo E, Diamandis EP. Peptidomics of Urine and Other Biofluids for Cancer Diagnostics. Clin Chem. 2014;60:1052-1061.

Drabovich AP, Martinez-Morillo E, Diamandis EP. Toward an integrated pipeline for protein biomarker development. BBA - Proteins and Proteomics 2014

Karagiannis GS, Treacy A, Messenger D, Grin A, Kirsch R, Riddell RH, Diamandis EP. Expression patterns of bone morphogenetic protein antagonists in colorectal cancer desmoplastic invasion fronts. Mol Oncol 2014;8:1240-1252 [PMID:24812030.

Leung F, Diamandis EP, Kulasingam V. Ovarian cancer biomarkers: current state and future implications from high-throughput technologies. Adv Clin Chem. 2014;66:25-77.

2015

Prassas I, Eissa A, Poda G,Diamandis EP. Unleashing the therapeutic potential of human kallikrein-related serine peptidases. Nat Rev Drug Discov 2015;14:183-202

Drabovich AP, Martinez-Morillo E, Diamandis EP. Toward an integrated pipeline for protein biomarker development. BBA - Proteins and Proteomics 2015;1854:677-686

Schully SD, Carrick DM, Mechanic LE, Srivastava S, Anderson GL, Baron JA, Berg CD, Cullen J, Diamandis EP, Doria-Rose VP, Goddard KAB, Hankinson SE, Kushi LH, Larson EB, McShane LM, Schilsky RL, Shak S, Skates SJ, Urban N, Kramer BS, Khoury MJ, Ransohoff DF. Leveraging biospecimen resources for discovery or validation of markers for early cancer detection. J Nat Cancer Inst 2015;107

Cretu D, Liang K, Saraon P, Batruch I, Diamandis EP, Chandran V. Quantitative tandem mass-spectrometry of skin tissue reveals putative psoriatic arthritis biomarkers. Clin Proteomics. 2015;12:1

2016

Li M, Diamandis EP. Technology-driven diagnostics: from smart doctor to smartphone. Crit Rev Clin Lab Sci. 2016:1-35.

Filippou PS, Karagiannis GS, Musrap N, Diamandis EP. Kallikrein-related peptidases (KLKs) and the hallmarks of cancer. Crit Rev Clin Lab Sci. 2016;17:1-58

Diamandis EP, Li M. The side effects of translational omics: overtesting, overdiagnosis and overtreatment. Clin Chem Lab Med 2016; 54:389-96.

Original Research Papers

2011

Eissa A, Amodeo V, Smith CR, Diamandis EP. Kallikrein-related peptidase-8 (KLK8) is an active serine protease in human epidermis and sweat and is involved in a skin barrier proteolytic cascade. J Biol Chem 2011;286:687-706.

Bayani J, Marrano P, Graham C, Zheng Y, Li L, Katsaros D, Lassus H, Butzow R, Squire JA, Diamandis EP. Genomic instability and copy-number heterogeneity of chromosome 19q, including the kallikrein locus, in ovarian carcinomas. Mol Oncol 2011;5:48-60.

Cramer DW, Bast RC Jr, Berg CD, Diamandis EP, Goodwin AK, Hartge P, Lokshin AE, Lu KH, McIntosh MW, Mor G, Patriotis C, Pinsky PF, Thornquist MD, Scholler N, Skates SJ, Sluss PM, Srivastava S, Ward DC, Zhang Z, Zhu CS, Urban N. Ovarian cancer biomarker performance in prostate, lung, colorectal and ovarian cancer screening trial specimens. Cancer Prev Res 2011;4:365-374.

Batruch I, Lecker I, Kagedan D, Smith CR, Mullen B, Grober E, Lo K, Diamandis eP, Jarvi KA. Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system. J Proteome Res 2011;10:941-953.

Nam RK, Kattan MW, Chin JL, Trachtenberg J, Singal R, Rendon R, Klotz L, Sugar L, Sherman C, Izawa J, Bell D, Stanimirovic A, Venkateswaran V, Diamandis E, Yu C, Loblaw DA, Narod SA. Prospective multi-institutional study evaluating the performance of prostate cancer risk calculators. J Clin Oncol 2011;29:2959-2964.

Guillon-Munos A, Oikonomopoulou K, Michel N, Smith CR, Petit-Courty A, Canepa S, Reverdiau P, Heuze-Vourc’h N, Diamandis EP, Courty Y. Kallikrein-related peptidase 12 hydrolyzes matricellular proteins of the CCN family and modifies interactions of CCN1 and CCN5 with growth factors. J Biol Chem 2011;286:25505-25518.

Cho C-K J, Drabovich AP, Batruch I, Diamandis EP. Verification of biomarker discovery approach for detection of Down syndrome in amniotic fluid via multiplex selected reaction monitoring (SRM) assay. J Proteomics 2011;74:2052-2059.

Dorn J, Madgolen V, Gkazepis A, Gerte T, Harlozinska A, Sediaczek P, Diamandis EP, Schuster T, Harbeck N, Kiechle M, Schmitt M. Circulating biomarker tissue kallikrein-related peptidase KLK5 impacts ovarian cancer patients’ survival. Ann Oncol 2011;22:1783-1790.

Dorn J, Harbeck N, Kates R, Ghazapis A, Scorilas A, Soosaipillai A, Diamandis E, Kiechle M, Schmalfeldt B, Schmitt M. Impact of expression differences of kallikrein-related peptidases and of uPA and PAI-1 between primary tumor and omentum metastasis in advanced ovarian cancer. Ann Oncol 2011;22:877-883.

Diamandis EP, Goodglick L, Planque C, Thornquist M. Pentraxin-3 is a novel biomarker of lung carcinoma. Clin Cancer Res 2011;17:2395-2399.

Makawita S, Smith C, Batruch I, Zheng Y, Ruckert F, Grutzmann R, Pilarsky C, Gallinger S, Diamandis EP. Integrated proteomic profiling of cell line conditioned media and pancreatic juice for the identification of pancreatic cancer biomarkers. Mol Cell Proteomics 2011;10:M111.008599.

Gratio V, Loriot C, Virca GD, Oikonomopoulou K, Walker F, Diamandis EP, Hollenberg MD, Darmoul D. Kallikrein-related peptidase 14 acts on proteinase-activated receptor 2 to induce signalling pathway in colon cancer cells. Am J Pathol 2011;179:2625-2636.

Kosanam H, Makawita S, Judd B, Newman A, Diamandis EP. Mining the malignant ascites proteome for pancreatic cancer biomarkers. Proteomics 2011;11:4551-4558.

Prassas I, Karagiannis GS, Batruch I, Dimitromanolakis A, Datti A, Diamandis EP. Digitoxin-induced cytotoxicity in cancer cells is mediated through distinct kinase and interferon signalling networks. Mol Cancer Ther 2011;10:2083-2093.

Drabovich AP, Jarvi K, Diamandis EP. Verification of male infertility biomarkers in seminal plasma by multiplex selected reaction monitoring assay. Mol Cell Proteomics 2011;10:M110-.004127.

Kulasingam V, Smith CR, Batruch I, Diamandis EP. Immuno-mass spectrometry: Quantification of low-abundance proteins in biological fluids. Methods Mol Biol 2011;728:207-218.

2012

Kosanam H, Sato M, Batruch I, Smith CR, Keshavjee S, Liu M, Diamandis EP. Differential proteomic analysis of bronchoalveolar lavage fluid from lung transplant patients with and without chronic graft dysfunction. Clin Biochem 2012;45:223-230.

Florentinus AK, Bowden P, Sardana G, Diamandis EP, Marshall JG. Identification and quantification of peptides and proteins secreted from prostate epithelial cells by unbiased liquid chromatography tandem mass spectrometry using goodness of fit and analysis of variance. J Proteomics 2012;75:1303-1317.

Rückert F, Aust D, Böhme I, Werner K, Brnadt A, Diamandis EP, Krautz C, Hering S, Saeger H-D, Grützmann R, Pilarsky C. Five primary human pancreatic adenocarcinoma cell lines established by the outgrowth method. J Surg Res 2012;172:29-39.

Batruch I, Smith CR, Mullen BJ, Grober E, Lo KC, Diamandis EP, Jarvi KA. Analysis of seminal plasma from patients with non-obstructive azoospermia and identification of candidate biomarkers of male infertility. J Proteome Res 2012;11:1503-1511.

Petraki C, Dubinski W, Scorilas A, Saleh C, Pasic MD, Komborozos V, Khalil B, Gabril M, Streutker C, Diamandis EP, Yousef GM. Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6 (KLK6) in colorectal cancer. Pathol Res Prac 2012;208:104-108.

Kagedan D, Lecker I, Batruch I, Smith C, Kaploun I, Kirk, L, Groban E, Diamandis EP, Jarvi K. Characterization of the seminal plasma proteome in men with prostatitis by mass spectrometry. Clin Proteomics 2012;9:2.

Seiz L, Dorn J, Kotzsch M, Walch A, Grebenchtchikov N, Gkazepis A, Schmalfeldt B, Kiechle M, Bayani J, Diamandis EP, Langer R, Sweep F, Schmitt M, Magdolen V. Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients. Biol Chem 2012;393:391-401.

Karagiannis GS, Petraki C, Prassas I, Saraon P, Musrap N, Dimitromanolakis A, Diamandis EP. Proteomic signatures of the desmoplastic invasion front reveal collagen type XII as a marker of myofibroblastic differentiation during colorectal cancer metastasis. Oncotarget 2012;3:267-285.

McDermed JE, Sanders R, Fait S, Klem RE, Sarno MJ, Adams TH, Diamandis EP. Nucleic acid detection immunoassay for prostate-specific antigen based on immuno-PCR methodology. Clin Chem 2012;58:732-740.

Kuzmanov U, Smith CR, Batruch I, Soosaipillai A, Diamandis A, Diamandis EP. Separation of kallikrein 6 glycoprotein subpopulations in biological fluids by anion-exchange chromatography coupled to ELISA and identification by mass spectrometry. Proteomics 2012;12:799-809.

Martinez-Morillo E, Diamandis A, Diamandis EP. Reference intervals and biological variation for kallikrein 6: Influence of age and renal failure. Clin Chem Lab Med 2012;50:931-934.

Martinez-Morillo E, Diamandis A, Romaschin A, Diamandis EP. Kallikrein 6 as a serum prognostic marker in patients with aneurysmal subarachnoid hemorrhage. PloS One 2012;7:e45676.

Saraon P, Musrap N, Cretu D, Karagiannis GS, Batruch I, Smith C, Drabovich AP, Trudel D, van der Kwast T, Morrissey C, Jarvi KA, Diamandis EP. Proteomic profiling of androgen-independent prostate cancer cell lines reveals a role for protein S during the development of high grade and castrate-resistant prostate cancer. J Biol Chem 2012;287:34019-34031.

Olkov-Mitsel E, Van der Kwast T, Kron KJ, Ozcelik H, Briollais L, Massey C, Recker F, Dwiatkowski M, Fleshner NE, Diamandis EP, Zlotta AR, Bapat B. Quantitative DNA methylation analysis of geners coding for kallikrein-related peptidases 6 and 10 as biomarkers for prostate cancer. Epigenetics 2012;7:1037-1045.

Martinez-Morillo E, Cho C-K, Drabovich A, Shaw J, Soosaipillai A, Diamandis EP. Development of a multiplex selected reaction monitoring assay for quantification of biochemical markers of Down syndrome in amniotic fluid samples. J Proteome Res 2012;11:3880-3887.

Prakash A, Rezai T, Krastins B, Sarracinol D, Athanas M, Russo P, Zhang H, Tian Y, Kulasingam V, Drabovich AP, Smith C, Batruch I, Oran LP, Fredolini C, Luchini A, Liotta L, Petricoin E, Diamandis EP, Chan DW, Nelson RW, Lopez MF. Inter laboratory reproducibility of SRM assays using multiple upfront analyte enrichment strategies. J Proteome Res 2012;11:3986-3995.

Drabovich AP, Pavlou MP, Dimitromanolakis A, Diamandis EP. Quantitative analysis of energy metabolic pathways in MCF-7 breast cancer cells by selected reaction monitoring assay. Mol Cell Proteomics 2012;11:422-434.

Petraki C, Yousef YM, Dubinski W, Lichner Z, Scorilas A, Pasic MD, Komborozos V, Khalil B, Streutker C, Diamandis EP, Yousef GM. Evaluation and prognostic significance of human tissue kallikrein-related peptidase 10 (KLK10) in colorectal cancer. Tumor Biol 2012;33:1209-1214.

Prassas I, Chrystoja CC, Makawita S, Diamandis EP. Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery. BMC Med 2012;10:39.

Ramachandran R, Eissa A, Mihara K, Oikonomopoulou K, Saifeddine M, Renaux B, Diamandis EP, Hollenberg M. Proteinase-activated receptors (PARs): Differential signalling by kallikrien-related peptidases KLK8 and KLK14. Biol Chem 2012;393:421-427.

Chen Y, Kinney L, Bozovic A, Smith H, Tarr H, Diamandis EP, LeBlanc A. Performance evaluation of Siemens ADVIA Centaur and Roche MODULAR Analytics E170. Total 25-OH Vitamin D assays. Clin Biochem 2012;45:1485-1490.

Leung F, Soosaipillai A, Kulasingam V, Diamandis EP. CUB and zona pellucida-like domain-containing protein 1 (CUZD1): A novel serological biomarker for ovarian cancer. Clin Biochem 2012;45:1543-1546.

Darling ME, Hashem NN, Zhang I, Mohamed AB, Fung K, Kwan K, Mara TW, Daley TD, Diamandis EP. Kallikrein-related peptidase 10 expression in salivary gland tissues and tumours. Int J Biol Markers 2012;27:e381-e388.

2013

Sölétormos G, Duffy MJ, Hayes DF, Sturgeon C, Barak V, Bossuyt PM, Diamandis EP, Gion M, Hyltoft-Petersen P, Lamerz RM, Nielsen DL, Sibley P, Tholander B, Tuxen MK, Bonfrer JM. Design of tumor biomarker-monitoring trials: a proposal by the European group on tumor markers. Clin Chem 2013;59:52-59.

Bayani J, Kuzmanov U, Saraon P, Fung WA, Soosaipillai A, Squire JA, Diamandis EP. Copy-number and expression alterations of miRNAs in the ovarian cancer cell line OVCAR-3: Impact on kallikrien 6 protein expression. Clin Chem 2013;59:296-305.

Eissa A, Cretu D, Soosaipillai A, Thavaneswaran A, Pellett F, Diamandis A , Cevikbas F, Steinhoff M, Diamandis EP, Gladman D, ChandranV. Serum kallikrein-8 correlates with skin activity, but not psoriatic arthritis, in patients with psoriatic disease. Clin Chem Lab Med 2013;51:317-325.

Saraon P, Cretu D, Musrap N, Karagiannis GS, Batruch I, Drabovich AP, van der Kwast T, Mizokami A, Morrissey CM, Jarvi K, Diamandis EP. Quantitative proteomics reveals that enzymes of the ketogenic pathway are associated with prostate cancer progression. Mol Cell Proteomics 2013;12:1589-1601.

Cho C-KJ, Drabovich AP, Karagiannis GS, Martinez-Morillo E, Dason S, Dimitromanolakis A, Diamandis EP. Quantitative proteomic analysis of amniocytes reveals potentially dysregulated molecular networks in Down syndrome. Clin Proteomics 2013;12:1589-1601.

Begcevic I, Kosanam H, Martinez Morillo E, Dimitromanolakis A, Diamandis P, Kuzmanov U, Hazrati L-N, Diamandis EP. Semiquantitative proteomic analysis of human hippocampal tissues from Alzheimer’s disease and age-matched control brains. Clin Proteomics 2013;10:5.

Kuzmanov U, Musrap N, Kosanam H, Smith C, Batruch I, Dimitromanolakis A, Diamandis EP. Glycoproteomic identification of potential glycoprotein biomarkers in ovarian cancer proximal fluids. Clin Chem Lab Med 2013;51:1467-1476.

Karagiannis GS, Berk A, Dimitromanolakis A, Diamandis EP. Enrichment map profiling of the cancer invasion front suggests regulation of colorectal cancer progression by bone morphogenetic protein antagonist, gremlin-1. Mol Oncol 2013;7:826-839.

Konvalinka A, Zhou J, Dimitromanolakis A, Drabovich AP, Fang F, Gurley S, Coffman T, John R, Zhang S-L, Diamandis EP, Scholey JW. Determination of an angiotensin II-regulated proteome in primary human kidney cells by stable isotope labelling of amino acids in cell culture (SILAC). J Biol Chem 2013;288:24834-24847.

Oikonomopoulou K, Deangelis RA, Chen H, Diamandis EP, Hollenberg MD, Ricklin D, Lambris JD. Induction of complement C3a receptor responses by kallikrein-related peptidase 14. J Immunol 2013;191:3858-3866.

Childs C, Martinez-Morillo E, Wai AP, Zu MM, Diamandis A, Diamandis EP. Exploring the relationship between serum biomarkers, acute intracerebral changes and outcome after severe traumatic brain injury (TBI). Clin Chem Lab Med 2013;51:e195-e197.

Kosanam H, Prassas I, Chrystoja CC, Soleas I, Chan A, Dimitromanolakis A, Blasutig IM, Rückert F, Gruetzmann R, Pilarsky C, Maekawa M, Brand R, Diamandis EP. Laminin, gamma 2 (LAMC2): A promising new putative pancreatic cancer biomarker identified by proteomic analysis of pancreatic adenocarcinoma tissues. Mol Cell Proteomics 2013;12:2820-2832.

Pavlou MP, Dimitromanolakis A, Diamandis EP. Coupling proteomics and transcriptomics in the quest of subtype-specific proteins in breast cancer. Proteomics 2013;13:1083-1095.

Makawita S, Dimitromanolakis A, Soosaipillai A, Soleas I, Chan A, Gallinger S, Haun R, Blasutig I, Diamandis EP. Validation of four candidate pancreatic cancer biomarkers identifies multiple panels to improve the performance of CA19.9. BMC Cancer 2013;13:404.

Leung F, Dimitromanolakis A, Kobayashi H, Diamandis EP, Kulasingam V. Folate-receptor 1 (FOLR1) protein is elevated in the serum of ovarian cancer patients. Clin Biochem 2013;46:1462-1468.

Radulovic M, Yoon H, Larson N, Wu J, Linbo R, Burda JE, Diamandis EP, Blaber SI, Blaber M, Fehlings MG, Scarisbrick IA. Kallikrein cascades in traumatic spinal cord injury: In vitro evidence for roles in axonopathy and neuron degeneration. J Neuropathol Exp Neurol 2013;72:1072-1089.

Schmitt M, Magdolen V, Yang F, Kiechle M, Bayani J, Yousef GM, Scorilas A, Diamandis EP, Dorn J. Emerging clinical importance of the cancer biomarkers kallikrein-related peptidases (KLK) in female and male reproductive organ malignancies. Radiol Oncol 2013;47:319-329.

Niederkofler EE, Phillips DA, Krastins B, Kulasingam V, Kiernan UA, Tubbs KA, Peterman SM, Prakash A, Diamandis EP, Lopez MF, Nedelkov D. Targeted selected reaction monitoring mass spectrometric immunoassay for insulin-like growth factor 1. PLOS ONE 2013;8:e81125

Drabovich AP, Dimitromanolakis A, Saraon P, Soosaipillai A, Batruch I, Mullen B, Jarvi K, Diamandis EP. Differential diagnosis of azoospermia with proteomic biomarkers ECM1 and TEX101 quantified in seminal plasma. Sci Transl Med 2013;5:212ra160.

Kepecs D, Zhang Y, Thai K, Advani S, Yuen D, Connelly K, Kosanam H, Diamandis EP, Sefton M, Gilbert R. Application of modular therapy for renoprotection in experimental chronic kidney disease. Stem Cells 2013;31:2408-19

2014

Saraon P, Trudel D, Kron K, Dimitromanolakis A, Trachtenberg J, Bapat B, van der Kwast T, Jarvi K, Diamandis EP. Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression. The Prostate 2014;74: 372-80.

Martinez Morillo E, Nielsen H, Batruch I, Drabovich A, Begcevic I, Lopez M, Minthon L, Bu G, Mattsson N, Portelius E, Hansson O, Diamandis EP. Assessment of peptide chemical modifications on the development of an accurate and precise multiplex selected reaction monitoring assay for Apolipoprotein E isoforms. J Proteome Res 2014;13:1077-87.

Karagiannis G, Schaeffer D, Cho C-K, Musrap N, Saraon P, Batruch I, Grin A, Mitrovic B, Kirsch R, Riddell R, Diamandis EP. Collective migration of cancer-associated fibroblasts is enhanced by overexpression of tight junction-associated proteins Claudin-11 and Occludin. Mol Oncol 2014;8:178-195.

Dorn J, Gkazepis A, Kotzsch M, Kremer M, Propping C, Mayer K, Diamandis EP, Kiechle M, Magdolen V, Schmitt M. Clinical value of protein expression of kallikrein-related peptidase 7 (KLK7) in ovarian cancer. Biol Chem 2014;395:95-107.

Prassas I, Brinc D, Farkona S, Leung F, Dimitromanolakis A, Chrystoja C, Brand R, Kulasingam V, Blasutig I, Diamandis EP. False biomarker discovery due to reactivity of a commercial ELISA for CUZD1 with cancer antigen CA125. Clin Chem 2014;60:381-8.

Karagiannis GS, Saraon, P, Jarvi K, Diamandis EP. Proteomic signatures of angiogenesis in androgen-independent prostate cancer. Prostate 2014;74:260-72.

Karagiannis GS, Pavlou MP, Saraon P, Musrap N, Xie A, Batruch I, Prassas I, Dimitromanolakis A, Petraki C, Diamandis EP. In-depth proteomic delineation of the colorectal cancer exoproteome: Mechanistic insight and identification of potential biomarkers. J Proteomics 2014;103:121-36.

Pavlou MP, Dimitromanolakis A, Martinez-Morillo E, Smid M, John A. Foekens JA, Diamandis EP. Integrating meta-analysis of microarray data and targeted proteomics for biomarker identification: application in breast cancer. J Proteome Res 2014;13:2897-909.

Martinez-Morillo E, Hernández PG, Begcevic I, Kosanam H, Garcia BP, Alvarez-Menéndez FV, Diamandis EP. Identification of novel biomarkers of brain damage in patients with hemorrhagic stroke by integrating bioinformatics and mass spectrometry-based proteomics. J Proteome Res 2014;13:969-81.

Cretu D, Prassas I, Saraon P, Batruch I, Gandhi R, Diamandis EP, Chandran V. Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry. Clin Proteomics 2014;11:27.

Smith CR, Batruch I, Bauça JM, Kosanam H, Ridley J, Bernardini MQ, Leung F, Diamandis EP, Kulasingam V. Deciphering the peptidome of urine from ovarian cancer patients and healthy controls. Clin Proteomics 2014;11:23.

Musrap N, Karagiannis GS, Saraon P, Batruch I, Smith C, Diamandis EP. Proteomic analysis of cancer and mesothelial cells reveals an increase in Mucin 5AC during ovarian cancer and peritoneal interaction. J Proteomics 2014;103:204-15.

Bery A, Leung F, Smith CR, Diamandis EP, Kulasingam V. Deciphering the ovarian cancer ascites fluid peptidome. Clin Proteomics 2014;11:13.

Kosanam H, Thai K, Zhang Y, Advani A, Connelly KA, Diamandis EP, Gilbert RE. Diabetes induces lysine acetylation of intermediary metabolism enzymes in the kidney. Diabetes 2014;63:2432-9.

Martínez-Morillo E, Hansson O, Atagi Y, Bu G, Minthon L, Diamandis EP, Nielsen HM. Total apolipoprotein E levels and specific isoform composition in cerebrospinal fluid and plasma from Alzheimer's disease patients and controls. Acta Neuropathol 2014;127:633-43.

Walker F, Nicole P, Jallane A, Soosaipillai A, Mosbach V, Oikonomopoulou K, Diamandis EP, Magdolen V, Darmoul D. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer. Biol Chem 2014;395:1075-86.

Sukumar N, Scott E, Dimitromanolakis A, Misiak A, Prassas I, Diamandis EP, Konvalinka A. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences. Biol Chem. 2014:395:1037-50

Satkunasivam R, Zhang W, Trachtenberg J, Ants T, Stanimirovic A, Yu C, Diamandis EP, Sugar L, Kattan MW, Narod SA, Nam RK. Human kallikrein-2 gene and protein expression predicts prostate cancer at repeat biopsy. Springerplus 2014;3:295.

Chan A, Prassas I, Dimitromanolakis A, Brand RE, Serra S, Diamandis EP, Blasutig IM. Validation of biomarkers that complement CA19.9 in detecting early pancreatic cancer. Clin Cancer Res 2014;20:5787-95.

2015

Cretu D, Liang K, Saraon P, Batruch I, Diamandis EP, Chandran V. Quantitative tandem mass-spectrometry of skin tissue reveals putative psoriatic arthritis biomarkers. Clin Proteomics 2015;12:1.

Dorn J, Bronger H, Kates R, Slotta Huspenina J, Schmalfeldt B, Kiechle M, Diamandis EP, Soosaipillai A, Schmitt M, Harbeck N. OVSCORE A validated score to identify ovarian cancer patients not suitable for primary surgery. Oncol Letters 2015; 9:418-424.

Korbakis D, Prassas I, Brinc D, Batruch I, Krastins B, Lopez MF, Diamandis EP. Delineating monoclonal antibody specificity by mass spectrometry. J Proteomics 2015;114:115-24.

Karagiannis GS, Musrap N, Saraon P, Treacy A, Schaeffer DF, Kirsch R, Riddell RH, Diamandis EP. Bone morphogenetic protein antagonist gremlin-1 regulates colon cancer progression. Biol Chem 2015;396:163-83.

Florentinus-Mefailoski A, Soosaipillai A, Dufresne J, Diamandis EP, Marshall JG. An enzyme-linked immuno-mass spectrometric assay with the substrate adenosine monophosphate. Anal Bioanal Chem 2015;407:1119-30.

Taylor DW, Ahmed N, Parreno J, Lunstrum GP, Gross AE, Diamandis EP, Kandel RA. Collagen Type XII and Versican are present in the early stages of cartilage tissue formation by both redifferentating passaged and primary chondrocytes. Tissue Eng Part A 2015;21:683-93

Lennox GK, Eiriksson LR, Reade CJ, Leung F, Mojtahedi G, Ferguson SE, Murphy J, Diamandis EP, Kulasingam V, Bernardini MQ. Effectiveness of the risk of malignancy index and the risk of ovarian malignancy algorithm in a cohort of women with ovarian cancer: does histotype and stage matter? Int J Gynecol Cancer 2015; 25:809-14.

Korbakis D, Brinc D, Schiza C, Soosaipillai A, Jarvi K, Drabovich AP, Diamandis EP. Immunocapture-selected reaction monitoring screening facilitates the development of ELISA for the measurement of native TEX101 in biological fluids. Mol Cell Proteomics 2015;14:1517-26

Grober E, Garbens A, Božović A, Kulasingam V, Fanipour B, Diamandis EP. Accuracy of testosterone concentrations in compounded testosterone products. J Sex Med 2015;12:1381-8.

Musrap N, Tuccitto A, Karagiannis GA, Saraon P, Batruch I, Diamandis EP. Comparative proteomics of ovarian cancer aggregate formation reveals an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). J Biol Chem 2015;290:17218-27

Yu Y, Prassas I, Dimitromanolakis A, Diamandis EP. Novel biological substrates of human kallikrein 7 identified through degradomics. J Biol Chem 2015;290:17762-75

Rotondo F, Di Ieva A, Kovacs K, Cusimano MD, Syro LV, Diamandis EP, Yousef GM. Human kallikrein 10 in surgically removed human pituitary adenomas. Hormones (Athens) 2015;14:272-9

Di Meo A, Rotondo F, Kovacs K, Cusimano Md, Syro Lv, Di Ieva A, Diamandis EP, Yousef GM. Human kallikrein 10 expression in surgically removed human pituitary corticotroph adenomas: An immunohistochemical study. Appl Immunohistochem Mol Morphol 2015;23:433-7

Korbakis D, Prassas I, Dimitromanolakis A, Davis GJ, Barber E, Reckamp KL, Blasutig I, Diamandis EP. Serum LAMC2 enhances the prognostic value of a multi-parametric panel in non-small cell lung cancer. Br J Cancer Supp 2015;113:484-91

Drucker KL, Gianinni C, Decker PA, Diamandis EP, Scarisbrick IA. Prognostic significance of multiple kallikreins in high-grade astrocytoma. BMC Cancer 2015;15:565

Martínez-Morillo E, Childs C, Prieto García B, Álvarez Menéndez FV, Romaschin AD, Cervellin G, Lippi G, Diamandis EP. Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury. Clin Chem Lab Med 2015;53:1575-84.

Duffy MJ, Sturgeon C, Barak V, Molina R, Hayes DF, Diamandis EP, Bossuyt P. Validation of new cancer biomarkers: A position statement from the European Group on tumor markers. Clin Chem 2015; 61:809-820

2016

Dukic L, Simundic AM, Martinic-Popovic I, Kackov S, Diamandis A, Begcevic I, Diamandis EP. The role of human kallikrein 6, clusterin and adiponectin as potential blood biomarkers of dementia. Clin Biochem 2016;49:213-218

Dorn J, Yassouridis A, Walch A, Diamandis EP, Schmitt M, Kiechle M, Wang P, Drecoll E, Schmalfeldt B, Loessner D, Kotzsch M, Magdolen V. Assessment of kallikrein-related peptidase 5 (KLK5) protein expression in tumor tissue of advanced ovarian cancer patients by immunohistochemistry and ELISA: correlation with clinical outcome. Am J Cancer Res 2016;6:61-70

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