Wednesday, February 12, 2014

HIghlights from Johns Hopkins Prostate Research Day: Another Huge Success for Prostate Research

The Johns Hopkins 9th Annual Prostate Research Day occurred this weekend, Saturday, February 8th, in Baltimore, Maryland.  The research presented at JHPRD is, in part, sponsored by the Patrick C. Walsh Prostate Research FundThe fund, started in 2005, is designed to attract outstanding scientists from the entire Johns Hopkins University who bring fresh thinking and new research initiatives. Each year a request for applications will be distributed to all scientists throughout Hopkins, soliciting their interest in applying for research funding in the field of prostate cancer and benign prostatic disease. The grants are reviewed by a scientific advisory board that awards funding to projects that hold the most promise.
Theodore DeWeese and Alan Partin listen to
presentations during the Research Updates.

In total, over 100 researchers and enthusiasts attended the lively and interactive meeting.  Among the guests were giants in the field of prostatic disease including Patrick C. Walsh, Alan W. Partin (Chairman and Urologist-in-Chief of the Brady), Donald S. Coffey, William Nelson (Director of the Sidney Kimmel Cancer Center at Johns Hopkins), Theodore DeWeese (Chairman of Radiation Oncology and Molecular Radiation Science), and Eric Klein (Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic), and many others.
Farsana Faisal, a medical student dedicating a year to
urology research, presents her work at the poster session.

Over 50 posters and presentations were dedicated to improving our understanding and treatment of prostate cancer and benign prostatic diseases.
Highlights from the day and Best Poster Presentations are detailed below.

Patrick C. Walsh Prostate Cancer Research Fund Progress Reports

Targeting the Angiogenic Switch in Prostate - Hans-Joerg Hammers, M.D., Ph.D.

Dr. Hammers presented an exciting update on his work of blood vessel growth in prostate cancer. The formation of new blood vessels is critical for prostate cancer progression and its ability to spread to the bones.  Importantly, the most commonly found protein in the bones, collagen, is intimately linked to the switch that allows new blood vessels to grow. This work has important implications for preventing the progression prostate cancer in the prostate and the treatment of prostate cancer that has spread to the bones.

Phase I Trial of HSP90 Inhibition and Radiation Androgen deprivation Therapy for High-Risk Localized and Locally Advanced Prostate Cancer - Phuoc Tran, M.D., Ph.D.


Based on available preclinical data, Dr. Tran theorizes that HSP90 inhibition will be a potent tumor specific radiosensitizer for prostate cancer and proposes a Phase I clinical trial of the HSP90 inhibitor, ganetespib, in high-risk/locally advanced prostate cancer patients with radiation and hormone therapy.  We expect to find the appropriate dose of ganetespib to be used in combination with radiation and androgen deprivation for future Phase II trials.  Ultimately, this Phase I trial will lay the ground work for subsequent trials to test the hypothesis that HSP90 inhibition can be a potent tumor selective radiosensitizer for prostate cancer treatment.

Epigenomic Effects of Chronic Inflammation in Prostate Cancer Initiation and Progression - V. Yegnasubramanian, M.D., Ph.D.

In a collaborative research project, a team of researchers, led by Drs. De Marzo, Bieberich, and Yegnasubramanian, are investigating the link between inflammation, molecular alterations to prostate cells, and prostate cancer. They are harnessing the power of cutting edge genetic models, genome-wide measurements, and molecular pathology to understand the mechanistic connections between inflammation, epigenetics, and prostate pathologies including cancer. This research could have major implications for prostate cancer prevention and interception.

Production and Evaluation of a PSA-Activated Human Serum Albumin/Proaerolysin Recombinant Protein as Novel Therapy for Metastatic Prostate Cancer -John Isaacs, Ph.D.

Dr. John Isaacs presented a novel concept, based on chemical engineering principles, of a unique molecule that is activated only in prostate cancer cells and creates a hole that is unrecoverable and leads to the death of that cell.

Structural and Biophysical Characterization of Gene Silencing by MBD2 Prostate Cancer - Daniel Leahy, Ph.D.

Dan Leahy spoke about a collaborative project between the Leahy, Nelson, and Yegnasubramian labs to investigate the molecular nature of interactions between MBD2 and methylated DNA and to identify and characterize inhibitors of this interaction.  MBD2 binds to methylated DNA and inhibits expression of nearby genes, including in many cases tumor suppressor genes in cancers. The goal of this work is to identify small molecules that will de-repress tumor suppressors and inhibit growth in cancer cells.

Novel Models of Prostatic Infection and Chronic Inflammation Using Human Prostate Cancer Derived Bacterial Isolates - Karen Sfanos, Ph.D.

Dr. Sfanos presented progress on a research project involving mouse models of prostate infections.  These models are being used to study the potential contribution of pathogenic microorganisms to the development of chronic inflammation in the prostate. This chronic inflammation may in turn serves to initiate and/or promote prostate cancer development. Notable findings to date include evidence that a single bacterial infection can induce long-term chronic inflammation in the mouse prostate that appears to be dependent on the type of infecting microorganism.

Evaluation of the Long Non-Coding RNAs, PRAC,  PRAC2 and Other Non-Coding Elements as Contributors To HOXB13-Induced Prostate Carcinogenesis - William B. Isaacs, Ph.D.

Dr. William Isaacs gave a wonderful review of the known genetic causes of prostate cancer.  He updated our knowledge of the HOXB13 gene and demonstrated that genetic contributors lead to earlier prostate cancer, specifically in men with high Gleason disease.

Update - Epidemiology of Prostate Cancer and Benign Prostatic Hyperplasia - Elizabeth A. Platz, Sc.D., MPH

Elizabeth Platz presented new findings from collaborative efforts that cross epidemiology, pathology, immunology, cancer biology, and urology at JH. She reported: 1) men with asthma were much less likely to develop lethal prostate cancer years later; 2) in men who did have an indication for biopsy and no diagnosis of prostate cancer, those who have a greater extent or intensity of inflammation in their prostates had higher serum PSA; and 3) men who are overweight/obese, inactive, or who smoke have shorter and/or more variable telomere length in their prostate stromal cells. She also described preliminary investigations on whether tissue-based prognostic markers are equally as informative in heavy and lean men and whether intraprostatic inflammation is related to the experience of LUTS. At each point in her presentation, Dr Platz challenged the attendees to pursue research that might uncover explanations for these observational findings, and to think about how these findings might be incorporated into models for patient management. At the end of her presentation, she reminded the attendees that population science on prostate cancer is more than just epidemiology. She introduced Dr. Craig Pollack, faculty at the Welch Center, and a primary care physician, who conducts healthcare delivery research on prostate cancer. She also mentioned Dr. Scott Zeger, faculty in the Department of Biostatistics and Vice Provost and Director of Hopkins inHealth, who is an expert in the development of new methods and big data. Dr. Zeger is a recipient of a PCW fund award with Dr. Carter.

2014 Prostate Research Day Poster Awards


1st Place Awards (Judge Arthur Burnett Award)

Androgen deprivation followed by acute androgen stimulation selectively sensitizes AR-positive prostate cancer cells to ionizing radiation
Mohammad Hedayati, Michael C. Haffner, Raju R. Raval, Yonggang Zhang, Haoming Zhou, Emma J. Knight, Susan Dalrymple, John T. Isaacs, Aileen Santos, Russell Hales, William G. Nelson, Srinivasan Yegnasubramanian, Theodore L. DeWeese.  

Novel interference of androgen receptor and Pol I in prostate cancer by non-competitive inhibition in vitro and in vivo
Paul Sirajuddin, Michael Moubarek, Jhanvi Patel, Zhiming Yang, Laureen Colis, Karita Peltonen, Hester Liu, Angelo De Marzo, Charles Bieberich, Marikki Laiho, 


Honorable Distinction, 2nd Place Award

A transgenic mouse model for inducible inflammation in the prostate.
Arya Ashok, Rebecca A. Walter, Varsha Rao, Laura N. Mutton, Michael Haffner, Angela Alme, Charles G. Drake, Srinivasan Yegnasubramanian, Angelo De Marzo, Charles J. Bieberich 


Honorable Distinction, 3rd Place Award

Mesenchymal stem cells (MSC) as cell-based vectors for PSA-activated Proaerolysin to sites of prostate cancer
W. Nathaniel Brennen, Oren Levy, Sudhir Ranganath, Michael Schweizer, David Marc Rosen, Sandrine Billet, Neil Bhowmick, Samuel Denmeade, Jeffrey Karp, John Isaacs.


Honorable Mention Awards

Functional screening identifies microRNAs which alter prostate cancer sensitivity to radiation therapy
Koji Hatano, Binod Kumar, Brian Mears, Wasim Chowdhury, Ronald Rodriguez, Mohammad Hedayati, Yonggang Zhang, Theodore L. DeWeese, Shawn Lupold.

Germline variants in the ASPORIN aspartic acid repeat domain and adverse prostate cancer outcomes
Paula Hurley, Debasish Sundi, Brian Simons, Robert Hughes, Guifang Yan, Marta Gielzak, David Berman, Sarah Isaacs, William Isaacs, Luigi Marchionni, Ashley Ross, Edward Schaeffer

PTEN loss predicts upgrading of prostate cancer from biopsy to radical prostatectomy
Tamara L. Lotan, Filipe L. Carvalho, Sarah B. Peskoe, Jessica L. Hicks, Jennifer Good, Helen Fedor, Elizabeth Humphreys, Misop Han, Elizabeth A. Platz, Jeremy A. Squire, Angelo M. DeMarzo, David M. Berman.

Mechanobiology and tumor growth: Multiphysics modeling, 3D cell culture
Sai Prakash, Sean Sun, Kenneth Pienta, 

Cyclin-dependent kinase 5(CDK5) controls prostate cancer metastasis in vivo and alters tumor immune response
B.W. Simons, A. Alme, C.F. Drake, B.D. Nelkin

Reclassification rates are higher among african american men than white men on active surveillance
D. Sundi, O. Kryvenko, J. Epstein, B.J. Trock, P.K. Landis, Z. Feng, A.E. Ross, H.B. Carter, E.M. Schaeffer


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