Research fellowships are available for one to three years for qualified urologists (and related specialists) seeking a productive research experience as the basis for a career in academic medicine. Clinical fellows spend 12 to 18 months (or longer) in research related to their academic interests.
Urology Service faculty are involved in many areas of research related to oncology, including minimally invasive surgery, medical informatics and outcomes research, pathology, radiology, clinical trials, or one of the many research laboratories at MSKCC, Weill Medical College of Cornell University, or The Rockefeller University. Urology fellows over the past five years have worked in immunology with Dr. Alan Houghton, in gene and cellular therapy with Dr. Michel Sadelain, and in cytogenetics with Dr. Raju Chaganti, among many other laboratories. Many fellows have successfully competed for individual funding for their research experience through American Urological Association Foundation Research Fellowships and American Cancer Society Fellowships, and we work closely with interested candidates to prepare competitive applications. The Urology Service also sponsors research fellowships through an NCI T32 training grant and the Career Development Program of the NCI SPORE in Prostate Cancer. In collaboration with the faculty, each fellow selects the research experience that best fits her/his interests and career plans.
Specific Research Opportunities
Biostatistics/Epidemiology/Outcomes
Ethan Basch, MD, MSc, is a health services researcher in the Department of Epidemiology and Biostatistics who studies clinical informatics and patient symptom self-reporting. As a medical oncologist he treats prostate cancer patients at the Kimmel Center. His recent research has focused on allowing patients to report their own toxicity-related symptoms during routine care and clinical trials. His other involvements include national informatics initiatives such as the cancer Biomedical Informatics Grid (caBIG) and the Clinical Data Interchange Standards Consortium (CDISC). Fellows interested in projects related to symptom assessment or the use of information technology during clinical trials are encouraged to participate in one of these programs.
Andrew Vickers, PhD, is a research methodologist in the Biostatistics Service, the broad focus of which is medical prediction. More specifically, our biostatisticians are interested in how predictions impact decision making. Much of their work concerns biomarkers, of which the best known is prostate-specific antigen (PSA). A typical issue that members of this team might examine is whether PSA levels can predict cancer recurrence, and if so, whether a prediction based on PSA levels is accurate enough to influence a clinical decision — for example, whether to offer adjuvant therapy. They also conduct research into various aspects of surgical quality, addressing questions such as whether outcomes vary between surgeons and what the “learning curve” is for particular surgical techniques.
Erectile Dysfunction
John P. Mulhall, MD, is Director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan-Kettering Cancer Center. His laboratory is focusing on two main endeavors. The first is to analyze the effect of cavernous neurotomy on the structure and function of corpus cavernosal smooth muscle and to explore methods of abrogating the deleterious effect of this nerve damage. Using a rat model, the laboratory is assessing the downstream effects of cavernous neurotomy as well as the impact of neuro protectants on nerve regeneration and survival of nerve grafts. They are also analyzing the utility of neurotracers injected in both antegrade and retrograde fashions to better identify the cavernous nerves. The fellow will work closely with Dr. Mulhall in designing and conducting the experiments, including IACUC liaison, animal microsurgery, and hands on exposure to the molecular techniques involved in the project.
The second main endeavor is to analyze the cellular mechanisms involved in the development of Peyronie's disease. This project involves both animal and molecular biologic research. Using a well-established cell culture model, molecular techniques such as PCR, RT-PCR, and viral transfection are being utilized to better understand this condition. SCID mouse experiments assess the pathobiology of Peyronie's disease plaque-derived fibroblasts that are cultured from patients and also are part of an effort to develop an animal model for this condition.
Immunology/Gene Therapy
Neil H. Bander, MD, developed the first and most successful monoclonal antibody against prostate specific membrane antigen(PSMA). His research focuses on the therapeutic activity of the naked monoclonal antibody, the development of conjugated antibody with cytotoxic compounds or with radio emitters for the therapy of prostate cancer, and the development of imaging tests using the radio labeledor fluorphore-labeled antibody. Both laboratory and clinical trials experience are available for fellows in his lab.
Michel Sadelain, MD, PhD, runs the Molecular Pharmacology and Chemistry Program at SKI. His lab is investigating the use of adaptive immunotherapy in the treatment of prostate cancer. Genetically modified cytotoxic T cells have been generated that express artificial receptors specific for prostate specific membrane antigen (PSMA). This system is currently being investigated in the treatment of local as well as metastatic prostate cancer in an in vivo model. Studies are also ongoing to explore the signaling properties of these receptors, alternative approaches to T cell activation and expansion, and homing properties in a metastatic model. It is hoped that these studies will lead to a novel approach to the treatment of prostate cancer.
Laparoscopic and Minimally Invasive Surgery Laboratory and Clinical Research
Karim A. Touijer, MD, and Jonathan Coleman, MD, supervise clinical and laboratory research in laparoscopic and robotic-assisted surgery and image guided procedures. The Urology Service at MSKCC is committed to determining the most appropriate applications of laparoscopy and minimally invasive techniques in the field of urologic oncology. The goal of the minimally invasive surgical research group, and therefore the research fellow, is to devise and test operative modifications, new techniques, and new technologies that will result in improvements in patient care. Because mastery of the laparoscopic techniques is indispensable to future innovation, dry laboratory facilities are available for every fellow who wants to improve his or her laparoscopic skill. Laparoscopic simulators, perfused-organs models, instrumentation to complete full laparoscopic training, and remote controlled manipulators (da Vinci and other robots) are available at any time. State of the art facilities include a live animal vivarium and allow for the critical evaluation of current laparoscopic and image-guided therapeutics as they apply to surgical outcome. The MIS program collaborates with bio engineering in instrument and bio material development for training, diagnosis, and therapeutics in MIS urologic oncology. Clinical research protocols in minimally invasive procedures explore the range of techniques applicable for the diagnosis and treatment of all urologic cancers, including cryoablation for renal tumors and MRI-directed prostate biopsy. The latter have been initiated, together with our colleagues in diagnostic and interventional radiology, to investigate the effective use of these techniques in urologic oncology care. Interested fellows will play a role in the critical steps of trial design and implementation as well as in the performence of percutaneous image guided procedures.
Pathology
Victor Reuter, MD, Vice Chair of the Department of Pathology, manages the Immunohistochemistry Core Laboratory. Fellows in his lab focus on clinical pathological correlations using detailed histologic and IHC analysis of surgical specimens. Dr. Reuter, who is also director of the SPORE Pathology Core, is particularly interested in prognostic features important in the biology and response to treatment of genitourinary cancers.
Radiology/Imaging
Hedvig Hricak, MD, PhD, is Chair of the Department of Radiology. She supervises a broad program of basic and clinical research in imaging urologic cancer, including prostate imaging using MRI and MRS (magnetic resonance spectroscopy). Clinical studies investigate the use of MRI for staging prostate cancer and for identifying features associated with increased perioperative morbidity. Expanding areas of research include molecular imaging, optical imaging, and the role of bladder imaging using MRI and MRS. In the animal lab, Dr. Jason Koutcher has developed a “micro MRI” for the serial measurement of tumors in mice.
Steven Larson, MD, is Chief of the Nuclear Medicine Service in the Department of Radiology and head of the Nuclear Medicine Research Laboratory in the Molecular Pharmacology and Chemistry Program of SKI. Dr. Larson is in charge of the Human PET and SPECT scanning facility and the micro PET scanner, which is designed for use with small animals. Dr. Larson's research goal is to achieve improved tumor diagnosis, treatment, and retreatment follow up through the use of radiotracers. The use of tissue and tumor specific antibodies and novel synthetic compounds, such as the G250 MoAb in renal cell cancer and CC-49 in colon and prostate cancer, is allowing Dr.Larson's team to identify and target solid tumors. His lab is exploring the potential of new antibodies against the external domain of PSMA as a potential prostate tumor radiotracer. Dr. Larson is also able to image the effectiveness of gene therapy using radiotracers and is analyzing this expression in patients.
Tumor Markers
Hans Lilja, MD, PhD, is a member of the Departments of Clinical Laboratories, Surgery, and Medicine. His research focuses on the mechanism of enzymes that are significant for the detection, progression, and monitoring of prostate cancer. Detection of increased extracellular release and sequestering of latent, active, and inactive forms of prostatic kallikreins (e.g., free and complexed PSA and hK2) provide extremely sensitive means to discover changes in tissue architecture that accompany the invasion and progression of prostate cancer lesions at an early stage. Recent studies from the Urologic Oncologic Research Laboratory demonstrate that there are significantly elevated levels of various PSA and hK2 forms in blood up to 20 years before men are diagnosed with clinically significant prostate cancer. The magnitude of extracellular release of active and latent protease forms parallels the invasion and progression of prostate cancer, and results in the activation of specific cascades that modify local regulatory target proteins in the extracellular micro environment of prostate cancer lesions. Data from the lab also suggest that the shedding of prostate cancer cells into the blood occurs at an early stage of disease while the tumor is still confined to the prostate. They hypothesize that the extracellular actions of prostatic kallikreins and related proteases are involved in tissue remodeling that enhances prostate cancer progression and results in the loss of the basal cell layer, basal lamina integrity, and the frequent shedding of prostate cells into blood. Selective, reliable, and early identification of men at high risk for prostate cancer, before they develop frequent shedding of prostate cells into the blood, may be a relevant target population for chemo preventive studies.
The team will use their findings on early disease specific, protease related patterns of prostate cancer to develop early risk group stratification, discriminate clinically significant from insignificant prostate cancer, identify noncurable disease, and monitor therapeutic efficacy. Novel principles of chemo prevention that block the activation of local growth stimulatory factors as a result of the release of latent and active forms of prostatic kallikreins and related proteases will be investigated.
