Center for Experimental Therapeutics : Projects

Multimodal Cure of Cancer

Project Investigator(s)
Toward the cure of adult acute lymphocytic leukemia: A personalized, genetic and epigenetic, chemo-immunotherapeutic approach Joseph Jurcic, MD; Renier Brentjens, MD, PhD; Cyrus Hedvat, MD, PhD; Ross Levine, MD; Peter Maslak, MD; Hans Guido Wendel, MD; Dan Douer, MD; Scott Armstrong, MD, PhD; Michael Kharas, PhD; David Scheinberg, MD, PhD
Changing the natural history of metastatic melanoma with multimodality therapy Neal Rosen, MD; Paul Chapman, MD; David Solit, MD; Scott Lowe, PhD; Jedd Wolchok, MD, PhD
Towards a cure for prostate cancer Charles Sawyers, MD; Jason Lewis, PhD; Dana Rathkopf, MD; Michael Zelefsky,MD
Curing ovarian cancer through early detection and personalized treatment David Spriggs, MD; Carol Aghajanian, MD; Douglas Levine, MD; Paul Sabbatini, MD

Multidisciplinary Team Research

Project Investigator(s)
Quillaja saponin adjuvants in carbohydrate conjugate cancer vaccines David Gin, PhD; Adam Boruchov, MD; Paul Chapman, MD; Govind Ragupathi, PhD and Jim Young, MD
Cellular target discovery and therapeutic agents — Proteases as targets for cancer therapy Yueming Li, PhD; David Scheinberg, MD, PhD; Xuejun Jiang, PhD and Johanna Joyce, PhD
Non-invasive imaging and monitoring of tumor hypoxia Clifton Ling, PhD; Jason Koutcher, MD, PhD; John Humm, PhD; Pat Zanzonico, PhD; Joseph O'Donoghue, PhD; and Ronald Finn, PhD
Development of active and adoptive immunotherapy of ovarian cancer targeting MUC16 and WT1 Philip Livingston, MD and Richard O'Reilly, MD
Development of rational strategies for anti-cancer therapy based on inhibition of signaling through the Ras and PI3kinase signaling pathways — Combined inhibition of Raf/MEK/MAPK and PI3K/AKT signaling for the treatment of cancer Neal Rosen, MD, PhD; PhD; Charles Sawyers, MD; David Solit, MD; and David Spriggs, MD
Targeting tumors with genetically enhanced T lymphocytes Michel Sadelain, MD, PhD; Prasad Adusumilli, MD; Renier Brentjens, MD, PhD; Vladimir Ponomarev, MD, PhD; Isabelle Riviere, PhD; Susan Slovin, MD, PhD
Functional and advanced anatomic techniques for response assessment in solid tumors Lawrence Schwartz, MD and Robert Motzer, MD
An integrated multidisciplinary approach to developing new treatments for advanced prostate cancer Derek Tan, PhD; Gabriela Chiosis, PhD; Yueming Li, PhD; Neal Rosen, MD, PhD and Howard Scher, MD
Identification of cell cycle related kinase inhibitors for cancer therapy Archie Tse, MD, PhD and David Spriggs, MD
Immunotherapy of cancer: Development of cancer vaccines, adoptive cellular therapies, immune modulation and combination immunotherapies Marcel van den Brink, MD, PhD; Ronald Blasberg, MD; Bo Dupont, MD, DSc; Alan Houghton, MD; Robert Jenq, MD; Steve Larson, MD; Jedd Wolchok, MD, PhD

Clinical Investigations

Project Investigator(s)
A phase I trial of malignant pleural mesothelioma treated with autologous T cells genetically targeted to the cancer cell Prasad Adusumilli, MD
Experimental Therapeutics Clinical Treatment Unit Richard Carvajal, MD
Vaccination of pancreatic cancer patients against mutated K-ras Paul Chapman, MD
Clinical translation of PU-H71, a small molecule Hsp90 inhibitor Gabriela Chiosis, PhD
Langerhans-type dendritic cell vaccination as consolidation for multiple myeloma after autologous stem cell transplantation David Chung, MD, PhD
Circulating tumor cells in patients with metastatic prostate cancer: Development of predictive biomarkers for sensitivity to androgen receptor targeted treatment sensitivity Daniel Danila, MD and Howard Scher, MD
Targeting Lewis Y in small cell lung cancer using the humanized monoclonal antibody, hu3S193 Chaitanya Divgi, MD
Cardenolides as novel agents for the treatment of retinoblastoma Hakim Djaballah, PhD and David Abramson, MD
Radioimmunotherapy, reduced-dose radiation therapy, and chemotherapy for medulloblastoma Ira Dunkel, MD and Kim Kramer, MD
Iso-fludelone, a novel epothilone: First in human phase 1 trial Mrinal Gounder, MD and Naiyer Rizvi, MD
Assessing the continual reassessment method as a phase I design by comparing it to the standard dose escalation scheme Alexia Iasonos, PhD
Pilot trial 89Zr-trastuzumab-PET as pharmacodynamic marker in patients with HER2-positive esophagogastric cancer Yelena Janjigian, MD
Hyperpolarized pyruvate MR imaging of prostate cancer Kayvan Keshari, PhD
Comparative analyses of WT1 expression and WT1 antigen-specific T-cell frequencies in patients with plasma cell leukemia following treatment with donor-derived Wilms tumor antigen-specific T lymphocyte infusions Guenther Koehne, MD, PhD
Development of KSR phosphorothioate antisense oligonucleotides for phase I clinical trial Richard Kolesnick, MD
Phase I study of intrathecal 131-I-8H9 for central nervous system and leptomeningeal malignancies Kim Kramer, MD
Pilot trial of a tetravalent KLH conjugate vaccine against small cell lung cancer Lee Krug, MD
Targeting small cell lung cancer with an Ac-labeled antibody to the ganglioside GD2 Lee Krug, MD
Phase I trial of a tetravalent vaccine with escalating doses of the immunological adjuvant QS-21, in combination with oral beta-glucan for high-risk neuroblastoma Brian Kushner, MD
Clinical and molecular-metabolic phase II trial of perifosine for recurrent/progressive malignant gliomas Andrew Lassman, MD
Combination of targeted radiotherapy and anti-angiogenesis for resistant neuroblastoma Shakeel Modak, MD
Lutetium-177 radiolabeled anti-prostate specific membrane antigen antibodies and its relationship to tumor-absorbed radiation dose Michael Morris, MD
Quantitative PET imaging with yttrium-86 radiolabeled humanized anti-prostate specific membrane antibody J591 for dosimetric evaluation of yttrium-90-huJ591 therapy Michael Morris, MD
Targeted radioimmunotherapy using Ley as a target in castrate metastatic prostate cancer Michael Morris, MD
Prostate specific membrane antigen vaccine in prostate cancer Luke Nordquist, MD
Preclinical and clinical development of 10-propargyl-10-deazaaminopterin (PDX) in relapsed or refractory aggressive non-Hodgkin's lymphomas Owen O'Connor, MD, PhD
A phase I clinical trial of a new targeted therapy for the treatment of metastatic pancreatic cancer Eileen O'Reilly, MD
GM-CSF DNA vaccine in melanoma Miguel Perales, MD
Phase 1 study of humanized 3F8 monoclonal antibody (Hu3F8) when combined with interleukin-2 in patients with high-risk neuroblastoma and GD2-positive solid tumors Stephen Roberts, MD
Preparation of a peptide vaccine for chronic myelogenous leukemia David Scheinberg, MD, PhD
Biomarker development in patients with metastatic prostate cancer: Assays for androgen receptor signaling pathway in circulating tumor cells Howard Scher, MD
Therapeutic response assessment in clinical trials: Development of tools for precise quantitative image analysis Lawrence Schwartz, MD
Synthesis of 150 grams of PDX Francis Sirotnak, PhD
Phase I trial of mouse TRP-2 DNA vaccine for patients with melanoma Jedd Wolchok, MD, PhD
Alemtuzumab treatment of steroid-refractory acute graft-versus-host disease James Young, MD

Drug Discovery and Development

Project Investigator(s)
Imaging the efficacy of TRAIL-enhanced cancer immunotherapy Prasad Adusumilli, MD and Vladimir Ponomarev, MD, PhD
Self-immolative tumor-targeted nanogenerators Christophe Antczak, PhD
Tumor endothelial cell-specific inhibitor for Id-proteins Robert Benezra, PhD
Over expression of asmase in endothelial stem cells by lentiviral vector delivery Nira Bloom, PhD
Expression and modulation of Fcγ receptors on human dendritic cells for targeted immunotherapy Adam Boruchov, MD
Mesoporous silica nanoparticles as drug delivery vehicles in a PDGFB-driven murine high grade glioma model Michelle Bradbury, MD, PhD
Construction and characterization of retroviral vectors encoding genes capable of generating both primary and efficient co-stimulatory signals to T cells for use in the adoptive immunotherapy of B cell malignancies Renier Brentjens, MD, PhD
Development and characterization of novel inhibitors of JAK kinases Jacqueline Bromberg, MD, PhD
Induction of natural EGFR inhibitors Luca Cartegni, PhD
Therapeutic modulation of alternative splicing Luca Cartegni, PhD
Dual specific human monoclonal antibody targeting IGF-I and IGF-II for treating cancer in children Nai-Kong Cheung, MD, PhD
Multistep targeting of GD2 using DOTA hook Nai-Kong Cheung, MD, PhD
Optimizing radioimmunotherapy delivered through cerebrospinal fluid: Testing affinity-matured scFv constructs in xenograft models Nai-Kong Cheung, MD, PhD
Humanized antibody targeting CSPG4 on melanoma Nai-Kong Cheung, MD, PhD
Novel compounds inhibiting Hsp90 Gabriela Chiosis, PhD and Neal Rosen, MD, PhD
Development of novel Hsp70 ATPase activity modulators Gabriela Chiosis, PhD
PU24FCl, a novel selective Hsp90 inhibitor Gabriela Chiosis, PhD
Bcr-Abl substrates and inhibitors Bayard Clarkson, MD
Leptin receptor as a target to eradicate CML tumor initiating cells Bayard Clarkson, MD
Development of D-peptide inhibitors of oncogenic KRAS mutants Samuel Danishefsky, PhD
Testing the immunogenicity of a new unimolecular hexavalent vaccine in combination with the novel synthetic saponin adjuvant SQS-1-0-5-5 Samuel Danishefsky, PhD
Cell migration inhibition: synthesis and evaluation of migrastatin and analogues for the identification of a novel chemotherapeutic Samuel Danishefsky, PhD
Preparation of multiple drug reversal agent 5-N-acetyl-ardeemin and some active analogues Samuel Danishefsky, PhD
Synthesis and evaluation of a novel unimolecular multiantigenic vaccine against breast cancer Samuel Danishefsky, PhD
Telomerase inhibition: Synthesis and evaluation of UCS1025A and analogues for the identification of a novel chemotherapeutic Samuel Danishefsky, PhD and Malcolm Moore, D.Phil.
Synthesis of a multi-scaffold library for high-throughput screening for novel inhibitors of androgen receptor signaling Christine DiBlasi, PhD
Synthetic study on proteasome inhibitor salinosporamide A Atsushi Endo, PhD
Novel enhancement strategies for cancer DNA vaccines: Epitope optimization and fusion vectors Manuel Engelhorn, PhD
Development of reagents to antagonize ceramide-mediated raft clustering in vivo Zvi Fuks, MD
High throughput screening of specific inhibitors for kinase suppressor of Ras1 (KSR1) Zvi Fuks, MD
ASMase gene therapy for radiosensitization Zvi Fuks, MD and Richard Kolesnick, MD
Preclinical development of anti-ceramide monoclonal antibodies Zvi Fuks, MD
Preclinical evaluation of KSR phosphorothioate antisense oligonucleotides in treating gf Ras-dependent human malignancies Zvi Fuks, MD and Richard Kolesnick, MD
The development of highly concise routes to epothilones in the context of the chemical synthesis of the promising antitumor agent 4-desmethyl-12,13-desoxyEpothilone B Ana Gabarda Ortega, PhD
Mechanism of TEM8 in increasing CD8 T cell responses Polly Gregor, PhD
Clinically approved nanoparticles as environmental-responsive self reporting drug delivery system Jan Grimm, MD, PhD
Multimodality theranostics of pancreas cancer Jan Grimm, MD, PhD
Gene expression profiling to identify therapeutic targets in chronic lymphocytic leukemia Mark Heaney, MD, PhD
Nanoscale bio-imaging Daniel Heller, PhD
ZIC1: Therapeutic target and predictor of outcome in adult male germ cell tumors Jane Houldsworth, PhD
Biodistribution and radiobiological effectiveness of 225Ac and 213Bi for alpha-particle radioimmunotherapy John Humm, PhD
Identification of chemical inhibitors of the ULK1 kinase complex Xuejun Jiang, PhD and Derek Tan, PhD
Identification and characterization of small molecule inhibitors of Apaf-1/Cytochrome c-mediated apoptosis Xuejun Jiang, PhD and Derek Tan, PhD
Targeting the PTEN ubiquitin ligase NEDD4 with a novel electrophilic fragment library Xuejun Jiang, PhD and Derek Tan, PhD
Chemical library screen for musashi inhibitors Michael Kharas, PhD
C16:0 ceramide nano-liposomes reverse multi-drug resistance Richard Kolesnick, MD
Small animal imaging and spectroscopy Jason Koutcher, MD PhD
Pre-clinical development of a novel class of proteasome inhibitors Marc Ladanyi, MD
Improved detection of abl, c-kit, src and PDGFRα expressing tumors using a combination of positron labeled EGFR tyrosine kinase inhibitors and “stealth” nanocarriers Steve Larson, MD
Radiosensitization of malignant gliomas by gene therapy Gloria Li, PhD and Philip Gutin, MD
Development of sulfonamide γ-secretase inhibitors for cancer therapy Yueming Li, PhD
Preclinical studies of sulfonamide γ-secretase inhibitors for cancer therapy Yueming Li, PhD
γ-Secretase: Target validation and inhibitor development Yueming Li, PhD
Target notch signal pathway in B-cell neoplasm Yueming Li, PhD
Develop protein methyltransferase inhibitors as anti-cancer drugs Minkui Luo, PhD
High-throughput screening for SETMAR inhibitors: Develop protein methyltransferase inhibitors as anticancer drugs Minkui Luo, PhD
High throughput screening for SETMAR inhibitors Minkui Luo, PhD
Synthesis of polyketide-like small molecule libraries Daniel Macks, PhD
Effect of histone deacetylase inhibitors on normal and transformed prostate cells Paul Marks, PhD
Monitoring molecular biomarkers in human cancer Peter Maslak, MD
A self-assembling synthetic clot to specifically infarct tumor tissue in vivo Michael McDevitt, PhD
RNAi prophylaxis of chemotherapy-induced nephrotoxicity Michael McDevitt, PhD
Optimizing EGFR Blockade in Human Glioblastoma Ingo Mellinghoff, MD
Evaluation of epothilone analogs, synthetic microtubule stabilizing agents with potent anti-myeloma and anti-ovarian cancer action Malcolm Moore, D.Phil.
Murine tumor xenograft models for preclinical drug development Malcolm Moore, D.Phil.
Function blocking antibodies against ADAM metalloproteases for inhibition of Eph, EGFR and Notch-dependent tumorigenesis Dimitar Nikolov, PhD
Small-molecule inhibitors of Eph receptor signaling Dimitar Nikolov, PhD
Real time polymerase chain reaction (PCR) for clinical and correlative studies Stephen Nimer, MD
The role of arginine methyltransferases in the pathogenesis of myeloid malignancies Stephen Nimer, MD
DNA vaccines against breast cancer: Synergy through targeting both tumor cells and tumor stroma Francesca Orlandi, PhD
Chemical synthesis in carbohydrate-based cancer vaccines Ouathek Ouerfelli, PhD
Overcoming acquired resistance to targeted therapy in lung cancer William Pao, MD, PhD
Protein chip biology system for high-thoughput screening Gavril Pasternak MD, PhD
Sigma receptors: a novel anti-proliferative target for tumor therapy Gavril Pasternak, MD, PhD
Structure activity of the sigma1 antagonist binding pocket Gavril Pasternak, MD, PhD
T-cell precursors and allogeneic hematopoietic stem cell transplant Miguel Perales, MD
SKI-N69: A candidate radiosensitizer John Petrini, PhD
Modulation of DNA damage signaling pathways John Petrini, PhD
Targeted nuclear delivery of EGF-Auger emitting radioconjugates for cancer therapy Nagavarakishore Pillarsetty, PhD
Evaluation of endothelial cell apoptosis in human cancer specimens in response to ionizing radiation Elizabeth Poyner, MD, PhD
Novel structure derivatives of trehalose dimycolate as cancer vaccine adjuvants Vivek Rao, PhD
Preclinical Testing of Hedgehog Inhibitors in Pancreatic Cancer Marilyn Resh, PhD
Identification of hedgehog palmitoylation inhibitors Marilyn Resh, PhD
Development and in vivo evaluation of clinical retroviral vectors designed to express high levels of mutant HSV thymidine kinase to increase the safety of T lymphocyte infusions Isabelle Riviere, PhD
Development of combined inhibition of ERK and PI3K/AKT signaling as a strategy for the treatment of mutant RAS-dependent tumors Neal Rosen, MD, PhD
Design of combinatorial therapeutics Chris Sander, PhD
Preclinical development of the anti-androgen A52 for prostate cancer therapy Charles Sawyers, MD
Therapeutic self-assembling nanodevices David Scheinberg, MD, PhD
Radiotherapy with targeted multivalent α-particle generators David Scheinberg, MD, PhD
A novel class of peptidomimetic agents targeting tumor growth, angio-genesis, and metastases Francis Sirotnak, PhD and David Scheinberg, MD, PhD
Modulation of chemotherapy sensitivity by alterations in PTEN/AKT signaling David Solit, MD
Characterization of an RNA binding protein targeted by thalidomide analogues David Spriggs, MD
MUC16 synthetic lethal screening in ovarian cancer David Spriggs, MD
Studying Chk1-mediated signaling pathways using chemical genetics and functional imaging Archie N. Tse, MD, PhD
Identification of novel small molecules with anti-proliferative action towards human lung cancer cell lines harboring oncogenic EGFR or KRAS Harold Varmus, MD
ESSENCE compounds as tools for specific modulation of alternative splicing patterns Sandra Vorlova, PhD
Defining the mechanism underlying GITR agonist activity Jedd Wolchok, MD, PhD
TMC-95A analogues as potential antitumor agents Zhi-Qiang Yang, PhD
Controlled rate freezer for preclinical laboratory studies James Young, MD
Janus kinase 2 (JAK2) as a therapeutic target in graft-versus-host disease James Young, MD and Brian Betts, MD
Reversal of indoleamine 2,3-dioxygenase (IDO)-mediated suppression of tumor immunity stimulated by human dendritic cells James Young, MD