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Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D.

Renata Pasqualini, Ph.D.
Professor
Genitourinary Med Onc - Rsch
University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd, Unit 0018-1, T7.3904
Houston, TX 77030
(713) 792-3872
(713) 404-0245 pager
rpasqual@mdanderson.org

Wadih Arap, M.D., Ph.D.
Professor,
Genitourinary Medical Oncology
University of Texas MD Anderson Cancer Center
1515 Holcombe Blvd, Unit 0018-1, T7.3904
Houston, TX 77030
(713) 792-3871
(713) 404-1429 pager
warap@mdanderson.org


As a matter of record, we have a long-standing collaboration and have led a joint laboratory (please note that we are husband-and-wife) since October 1999. From our arrival at MDACC, we have jointly published over 100 original peer-reviewed research manuscripts and, with very few exceptions, such publications are a team science effort. Our research group currently includes 8 graduate or M.D./Ph.D. students, 12 postdoctoral fellows, 3 faculty (assistant and associate professors), 5 research technicians, and 4 administrative staff members. Our central working hypothesis is that differential protein expression in the human vascular endothelium associated with normal or diseased tissues offers the potential for developing novel diagnostic, imaging, and therapeutic strategies. In essence, our research program uses combinatorial library selection (peptide- and antibody-based) to discover, validate, and exploit the vascular biochemical diversity of endothelial cell surfaces towards a new vascular-targeted pharmacology. Such targeting technologies may lead to the development of ligand-directed agents for application in the treatment of cancer patients. Translational applications, such as first-in-man clinical trials, which have now started within the institution, will ultimately determine the value of this strategy. Indeed, the Food and Drug Administration (FDA) has granted a “safe-to-proceed” status for our first vascular-targeted IND in 2009. A first-in-human study has already been initiated with several patients enrolled in this MDACC-sponsored clinical trial. A second IND was filed mid-November 2010, two other drugs are in pre-IND stage, and several others in pre-clinical laboratory phase. Long-term, the broader vision of our research is a large-scale mapping of receptors in human vasculature towards a new ligand-directed pharmacology. In this Preface, only a summary of milestones and timelines is provided as follows:

The Human Vascular Mapping Project

  • 2000: Scientific & ethical framework for human experimentation (Arap et al. 2002)
  • 2002: Combinatorial screening in brain-dead and terminal wean patients (Arap et al. 2002)
  • 2004: Validation of the IL-11 receptor as a target in prostate cancer (Zurita et al. 2004)
  • 2005: Intra- and inter-institutional ethics guidelines (Pentz et al. 2003, Pentz et al. 2005)
  • 2006: Design and validation of synchronous experimental approach (Kolonin et al. 2006)
  • 2008: Serial synchronous selection adapted for selection in patients (Staquicini et al. submitted)
  • 2009: Translation of a targeted peptidomimetic (BMTP-11) in a first-in-man trial (Millikan/Logothetis et al. ongoing)
  • 2010: Drug localization established in bone metastasis biopsies in 6 out of 6 patients treated
  • 2010: BMTP-11 was licensed to Mercator Therapeutics, a new biotech company based on Boston.
  • 2010: Patient biopsy and autopsy material processed and captured on a data base with more than 2 MM ligands

Ligand-directed Targeting, Nanotechnology & Molecular-genetic Imaging

  • 1998-2000: Tumor targeting in preclinical models (Arap et al. 1998; Pasqualini et al. 2000)
  • 2003: Display of combinatorial peptide libraries on AAV particles (Müller et al. 2003)
  • 2005: Self-assembled biocompatible Au-phage network (Souza et al. 2006a; Souza et al. 2006b)
  • 2006: AAV-phage (AAVP) for molecular imaging (Hajitou et al. 2006; Hajitou et al. 2007)
  • 2008: AAVP predicts drug response in sarcoma: towards an imaging transcriptome (Hajitou et al. 2008)
  • 2009: Phase I-II of trial of targeted TNF in pet dogs with spontaneous cancer (Paoloni et al. in press)
  • 2010: Plans for collaborative work with Pharma engaged

Fingerprinting the Repertoire of Patient-derived Antibodies

  • 2000: Technology design and optimization
  • 2001: Human prostate cancer serum sample selection
  • 2003: Fingerprinting antibodies from cancer patients (Mintz et al. 2003; Vidal et al. 2004)
  • 2004: Validation of GRP78 as a target in prostate and breast cancer (Arap et al. 2004)
  • 2008: Horizontal follow-up of humoral response in patients (Mintz et al. submitted)
  • 2009: Functional definition of human CLL based on fingerprinting BCR (Binder et al. Cancer, 2010)
  • 2010: Fingerprinting antibodies from patients with Hodgkin’s disease (Yao et al., submitted)

Obesity Reversal through Vascular Targeting

  • 2004: Targeted treatment in preclinical models of obesity (Kolonin et al. 2004)
  • 2007: GMP grade peptidomimetic drug custom-ordered and received
  • 2009: Activity and toxicity study in obese baboons and Rhesus monkeys (Barnhart et al. in preparation)
  • 2009: Direct selection of ligands to human white adipose tissue in cancer patients (Kolonin et al. in preparation)
  • 2009-2010: IND filed for a Phase I clinical trial in obese prostate cancer patients phase (Millikan/Logothetis et al. anticipated)

Hybridoma-free Generation and Production of Antibodies

  • 2003: Technology design and development
  • 2004: Hybridoma-free monoclonals: concept and reduction to practice (Pasqualini & Arap 2004)
  • 2009: De novo generation of a new transgenic ImmortoXenomouse (Rangel et al. ongoing)
  • 2010: Targeted imaging using loop grafted tumor homing peptides (Driessen et al., ongoing)

Read more about the research of Drs. Pasqualini and Arap in the attached profile (pdf).


© 2014 The University of Texas MD Anderson Cancer Center