Saturday November 01, 2014   
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Research Grants

 

Clinical Trials
Led by Steven S. Rosenfeld, MD, PhD at New York-Presbyterian Hospital/Columbia University’s Brain Tumor Center

The Gary Lichtenstein Memorial Grant

In the second year of a grant from VABC, the Brain Tumor Center has grown to be one of the largest in the Northeast with the addition of 10 phase I, II, and III clinical trials that are or will soon be available for patients. Columbia has also been invited to join a new national, multi-institutional brain cancer clinical investigative consortium, as a direct result of their success in attracting pharmaceutical and biotech companies to be included in their trials. Finally, the Center’s research has led to the discovery of GBM’s sensitivity to Sutent, an FDA-approved anti-cancer drug. Dr. Rosenfeld will start treating GBM patients with Sutent in order to determine the effectiveness of this medication.

“The investment that VABC has made in our program has been leveraged into a much larger return, and we fully expect that with further support from VABC, we will continue to grow rapidly and provide our patients with more state of the art therapies.”
- Steven S. Rosenfeld, MD, PhD
VABC grant recipient

Research Summary
From the desk of Steven S. Rosenfeld, M.D. Ph.D.
Professor of Pathology, Neurology, Anatomy & Cell Biology, Columbia University Medical Center and Chief, Division of Neuro-Oncology & Co-Director, The NewYork-Presbyterian Hospital Brain Tumor Center

My laboratory is interested in understanding at a molecular level how the physiologic requirements placed on an enzyme shape its function. We are addressing this concern by focusing on a group of enzymes called “molecular motors”. These enzymes drive a wide variety of physiologic processes, from whole cell motility to vesicle transport to separation of the chromosomes during mitosis. As such, they represent potential targets for the development of new therapies for diseases characterized by abnormal cell motility and cell growth, such as cancer. We utilize a variety of spectroscopic methodologies, including fluorescence resonance energy transfer, fluorescence anisotropy decay, and resonance Raman spectroscopy to examine how functionally important domains within motors contribute to generating force and movement. We also combine these structurally-sensitive probes with transient state kinetics to determine the timing and sequence of conformational changes in each motor’s mechanochemical cycle.

I have largely focused my research on two classes of molecular motors–the myosins and kinesins. Current research in my laboratory on myosin is examining the sequence of structural changes that occur in transport myosins, such as myosins V and VI, that explain how these motors are capable of moving long distances on actin filaments without dissociating–a feature called “processivity”. My work on the kinesin family of motors has largely focused on the mechanisms of processivity of kinesin I. However, I have more recently been interested in studying those kinesins that drive formation of the mitotic spindle, referred to as “mitotic” kinesins.

Finally, I am applying the spectroscopic assays of motor function developed in my laboratory to a microtiter well platform, in collaboration with investigators at the University of Pittsburgh, to screen for small molecule inhibitors of mitotic kinesins, which may ultimately be applicable clinically as inhibitors of mitosis.

 


Update, 2008
From Steven S. Rosenfeld, M.D. Ph.D.

 

Over the course of this period of time, we have accomplished the following:

  • Research Nurse: Thanks to support from VABC, we have been able to hire Mahogany Ayele, MS, RN, who has been very effective in accomplishing all of the goals listed under Request #1. We have successfully activated 10 phase I, II, and III clinical trials (see table below) that are available to our patients, and which represent novel agents that would not be available to our patients without the VABC support.

    The importance of this nurse to our overall function is underscored by the fact that while we were only able to accrue 8 patients to clinical trials between 2005-2007; we were able to accrue 52 patients between 2007-2009, and anticipate even more robust enrollment figures for the next two years.

  • BTIC Membership: Thanks in part to our success in rapidly building a clinical investigative infrastructure–due to VABC support–we were able to successfully petition for entry into the Brain Tumor Investigators’ Collaborative (BTIC). This consortium consists of nine institutions, including Stanford, Cedars Sinai Medical Center, University of Washington, Barrow Neurological Institute, University of Florida, Huntsman Cancer Center (Utah), Tufts, Dartmouth-Hitchcock, and Columbia, and its mission is to rapidly accrue patients with malignant brain tumors to phase II trials. We are currently completing the first phase II trial (Azixa) and are negotiating with Genentech for a new phase II trial of Avastin in elderly patients with malignant glioma.
  • Symptom Management Clinic: VABC support has allowed our research nurse, in collaboration with our clinical nurse practitioners and social worker, to establish a weekly clinic in which they meet with our patients to address the large number of psychosocial issues and problems that accompany the diagnosis and treatment of a malignant glioma. This clinic also serves as a venue for introducing the information manual jointly produced by Columbia University and VABC.
  • Tumor Tissue Banking: Dr. Rose Lai, in collaboration with members of the Biostatistical Core of the Herbert Irving Cancer Center, has developed a web-based database that links all clinical information on our patients to a brain tumor tissue bank housed within the Cancer Center. This resource is currently being used by several neuro-oncology investigators to correlate clinical outcome with molecular markers of tumor response. The database is also compatible with the much larger Velos database, that is used by the Cancer Center for all of its clinical trial management.
  • Development of Case Report Forms: Our success in hiring Ms. Ayele, MS, RN, with support from VABC, in turn allowed us to successfully receive support from the Herbert Irving Comprehensive Cancer Center for a full-time data manager, whose responsibilities include generation of case report forms and enrollment forms, and oversight of the statistical needs for each study.

Click here for a full list of research grants funded by Voices Against Brain Cancer.

 

 
Voices Against Brain Cancer is a not-for-profit public charity recognized by the IRS under 501 (c) (3)