Seminar 4:30 − 5:15 pm
Discussion 5:15 − 5:30 pm

February 1, 2010

Hamid Mirzaei, PhD
Res Sci, Inst for Sys Bio Targeted Mass Spectrometry (SRM): a new approach to quantitative proteomics
Abstract:
Systems biology depends intimately on the ability to make quantitative measurements of transcriptome, proteome and metabolome. To answer this need, quantitative proteomics has grown in the last 6-7 years, to become a major source of information for systems biology studies where iterative measurements of reproducible sets of proteins from differentially perturbed biological states are essential. A more recent development in the field of quantitative proteomics is Selected Reaction Monitoring (SRM). This mass spectrometry based technology is aimed at fast, sensitive and reproducible screening of large sets of known targets and is ideal for building biological assays in which the presence and quantity of specific analytes is being determined in multiple samples. We applied this technology to study gene regulation in yeast by developing SRM assays for the entire yeast transcription machinery that includes more than 400 proteins. We used this assay to dissect the most complicated gene promoter in yeast (FLO11) in order to understand how it is regulated. We also applied this technology to study protein ubiquitination. We developed a set of SRM assays to determine the frequency of different types of inter-ubiquitin linkages in polyubiquitin chains relative to total ubiquitin concentration. We used this assay to explore changes in poly-ubiquitination of single proteins and the whole proteome under various stress conditions. We demonstrated that SRM is a highly sensitive and quantitative technology that can be used to measure proteins rapidly and reproducibly.

February 8, 2010

A pluripotency signature predicts transformation and survival in follicular lymphoma patients
Andrew J Gentles, PhD
Research Associate, Stanford School of Medicine
Absract
Transformation of follicular lymphoma (FL) to diffuse large B cell lymphoma is associated with accelerated disease course and drastically worse outcome, yet the underlying mechanisms are poorly understood. Our computational analysis of expression data suggests that a network of gene transcriptional modules underlies transformation. Central to the network hierarchy is a signature that is strikingly enriched for pluripotency - related genes. These genes are typically expressed in embryonic stem cells (ESC), including MYC and its direct targets. The ESC program is correlated with transcriptional programs maintaining tumor phenotype in transgenic MYC - driven mouse models of lymphoma. A model based on ESC/differentiation programs stratifies patient outcomes in the training dataset as well as in an independent validation set, and is predictive of propensity of FL tumors to transform. Transformation is associated with an expression signature combining high expression of ESC transcriptional programs in combination with reduced stromal signaling. Together, these findings suggest a central role for an ESC - like signature in the mechanism of transformation and provide new clues for potential therapeutic targets. I will also describe how the approach can generalize to other cancers, leveraging large cancer datasets to identify key processes and molecules involved in early stages of the disease.

February 22, 2010

Alway Bldg, Rm M114
Samuel A. Wickline, M.D.
Prof. of Med, Biomed Eng, Phys, & Cell Bio
Dir, C-TRAIN
Washington University

Perfluorocarbon nanosystems for quantitative molecular imaging and therapy
Abstract:
The goal of Nanomedicine is to develop new diagnostic and therapeutic agents derived from fundamental discoveries in nanotechnology that can be applied safely and efficaciously in the treatment of human diseases. We have developed a number of platforms that meet these goals that have now progressed to clinical trials. In particular, emulsion based nanoparticle comprising perfluorocarbon cores and lipid-surfactant shells can be functionalized with imaging agents, drugs, genes, and targeting moieties to bind to specific molecular epitopes for both sensitive image-based detection and drug delivery at high local concentrations. Novel methods for the use of MRI, ultrasound, CT, optical and nuclear diagnostics have been developed. Drug delivery through unique mechanistic pathways involving fusional complexation of soft nanoparticles with cell membranes transports drugs (small molecules, cytolytic peptides, oligonucleotides, etc.) to cytoplasm for immediate effect. Novel pharmacokinetic approaches allow quantification of local drug delivery based on noninvasive imaging readouts. These and other innovations promise to alter the traditional paradigm for delivery and monitoring of therapeutic agents by taking advantage of targeted delivery at low serum concentrations that should reduce side effects while improving selective deposition of agents at greater concentrations than can be achieved by traditional diffusional mechanisms.

March 22, 2010

Jens Hasseroot, PhD
Professor, Chemistry Laboratory, University of Lyon, France

Designing Molecular Probes for MRI and Fluorescence Imaging that Detect Enzyme Activity

March 29, 2010

Imaging Dementia
Minal Vasanawala, MD
Stanford Nuclear Medicine Clinic, VA

April 5, 2010

A New Therapeutic Approach for Treating Receptor Negative Breast Cancers
Ramasamy Paulmurugan, PhD
Assistant Professor, Stanford University

April 12, 2010

Jason S. Lewis, PhD
Vice Chair, Basic Research
Sloan-Kettering Cancer Ctr

Targeted Radiopharmaceuticals: New Insights into Cancer
Abstract:
The use of Positron Emission Tomography (PET) for cancer imaging is a well-established and widely used molecular imaging modality both in clinical and research settings. PET offers the ability to quantitatively measure biological and receptor-based processes using a wide spectrum of specifically designed radiopharmaceuticals. The use of PET is expanding and the inclusion of longer-lived radiometal positron-emitters is broadening the application and appeal of this imaging modality.

Dr. Lewis' research interests are focused on the development of new PET radiopharmaceuticals for the diagnosis and treatment of cancer. His work incorporates F-18, C-11, and nonstandard nuclide radiopharmaceutical development, with an emphasis on cancer detection and therapy. The Lewis Lab works on the development of small molecules, radiolabeled peptides and antibodies that target the overexpression of receptors and antigens on tumors as well as imaging changes in the tumor microenvironment associated with malignancy.

This presentation will review the current state-of-the-art in non-standard PET nuclide application with an emphasis on the use of radiometals with peptide and antibody constructs. In addition, since the effective use of a radiometal nuclide often relies on their attachment to the targeting probe via a bifunctional chelator, this talk will focus on novel strategies for using “click” chemistry methodology for attachment of the radiometals to active biomolecules.

April 19, 2010

Time-of-flight positron emission tomography (ToF-PET): study of detector attributes for sub-nanosecond timing
Virginia Spanoudaki, PhD Levin Lab

April 26, 2010

Molecular Correlates of Dynamic Contrast-Enhanced MRI in Locally Advanced Breast Cancer
Nick Hughes Gambhir Lab

May 10, 2010

Badri Roysam, PhD
Prof, Rensselaer Polytechnic Inst

Quantifying Structures and Phenomena in Complex and Dynamic Biological Microenvironments from 4D/5D Optical Microscopy Data

Abstract:

Many tissue microenvironments that play critical roles in health and disease are complex and dynamic, e.g., tumors, stem-cell niches, brain tissue surrounding neuroprosthetic devices, retinal tissue, cancer stem-cell niches, glands, and immune system tissues. Progress in these areas is much too slow compared to the need. Knowledge is pieced together from large numbers of experiments, each of which yields a small amount of information. Much of the knowledge still remains qualitative. There is a compelling need to accelerate progress towards a quantitative understanding. I will describe strategies based on multi-dimensional optical microscopy and computational image analysis.

Modern optical microscopy has grown into a multi-dimensional imaging tool. It is now possible to record dynamic processes in living specimens in their spatial context and temporal order, yielding information-rich 5-D images (3-D space, time, spectra). The task of analyzing these images exceeds human ability. There is a need for automated systems to map the tissue anatomy, quantify structural associations, identify critical events, map event locations and timing, identify and quantify spatial and temporal dependencies, produce meaningful summaries of multivariate measurement data, and compare 4-D/5-D datasets for testing hypotheses, exploration, and systems modeling. Importantly, there is a need for "computational sensing" methods capable of exceeding human ability.

In this talk, I will use examples from neuroscience, cancer histopathology, immunology, and retinal stem-cell biology to show the practicality of multi-dimensional image analysis and computational sensing.

May 17, 2010

Imaging changes in stem cell fate
Helen Blau, PhD
The Donald E. and Delia B. Baxter Professor of Pharmacology and Professor of Chemical and Systems Biology
Stanford

June 7, 2010

Imaging and Therapy of the Vessel Wall
Mike McConnell, MD, MSEE
Cardiovascular Medicine, Stanford

June 14, 2010

Viking Treasure: Digging through the Recent ISMRM Meeting in Stockholm.
Michael E Moseley, PhD
Professor of Radiology, Stanford

June 28, 2010

Dual Axis Microscopes for Point of Care Microscopy
Christopher Contag, PhD
Associate Professor of Pediatrics and of Microbiology and Immunology and, by courtesy, of Radiology,
Stanford

July 12, 2010

Immobilization Bed for pre-clinical CT/PET/Optical imaging
Geoff Nelson
Graduate Student, Graves Laboratory

July 19, 2010

Zahi A Fayad, MD
Prof of Radiology
Dir, Translational and Molecular Imaging Institute
Mt. Sinai Med Sch

Whole-body MR-PET, Multimodal Imaging and Drug Delivery in Atherosclerosis

Abstract:
Atherosclerosis is an inflammatory disease, where the degree of inflammation, not the plaque size, determines risk of rupture and therefore likelihood of a clinical event. Magnetic Resonance Imaging (MRI) can image atherosclerotic plaque with high resolution, and several MRI parameters of disease extent in the carotid arteries and aorta have been shown to correlate with atherosclerotic risk factors. Dynamic-contrast-enhanced MRI (DCE-MRI) is a new technique for the study of plaque composition. In this study, the extent of plaque inflammation determined by FDG uptake was correlated with DCE-MRI. By providing a metabolic image of macrophage activity, F18-Fluorodeoxuglucose (FDG) positron emission tomography (PET) can image atherosclerotic plaque inflammation in patients and in animal models of disease, with a strong correlation between FDG uptake and plaque macrophage content. In addition, autoradiography has confirmed that the FDG signal originates from activated macrophages within the lipid core and fibrous cap of the plaque. This has led to the suggestion that FDG-PET might have a role in identifying ‘high risk’ plaques and monitoring their response to therapy. Computed tomography (CT) can be used in conjunction with PET to help co-register the PET images and for attenuation corrections. Moreover, CT with its exquisite coronary imaging has the potential to address atherosclerosis in the vessel wall of the coronary arteries. We review in this talk to use of multimodality imaging (MR, PET, and CT), the emergence of combined MR/PET scanners and the use of nanotechnology to improve molecular imaging and drug delivery in atherosclerosis.

July 26, 2010-4:00pm

August 2, 2010

High Field and Molecular MRI

Brian Rutt, PhD
Professor of Radiology

August 9, 2010

Ralph P Mason, PhD
Professor, UT Southwestern Medical Center

Tumor hypoxia-assessing and exploiting oxygen dynamics in cancer therapy

Abstract:
Hypoxia has long been recognized to influence solid tumor response to therapy. Increasingly, hypoxia has also been implicated in tumor aggressiveness, including growth, development and metastatic potential. Thus, there is a fundamental, as well as a clinical interest, in assessing in situ tumor hypoxia and Dr. Mason's Laboratory for Prognostic Radiology is developing MRI methods for assessing tumor oxygen dynamics. A primary focus has been 19F MRI oximetry, which reveals not only hypoxia in vivo, but more significantly, dynamics of spatial distribution of pO2 quantitatively, with a precision relevant to radiation therapy. In addition recent studies suggest that non-invasive BOLD (blood oxygen level dependant) and TOLD (tissue oxygen level dependant) measurements may provide predictive biomarkers suitable for use in patients, where measurements should be non-invasive. Dr. Mason will discuss recent translation to clinical studies in breast, cervix, lung and prostate at UT Southwestern.

Aug 16, 2010

TBA

Nan Ma, Rao Laboratory

Aug 23, 2010

Aug 30, 2010

Modeling pathogenesis and treatment of familial hypertrophic cardiomyopathy using patient-specific iPSCs
Feng Lan, PhD, Wu Lab

September 13, 2010

Venu Raman, PhD
Associate Professor, Radiaiton & Oncology
Johns Hopkins School of Medicine

RNA Helicases: The Next Generation of Targets for Cancer Treatment
Abstract:
Effective treatment of cancers is a major challenge to the medical community. A majority of the current chemotherapeutic agents damage DNA or target the mitotic pathway. This approach has been successful to a degree but also induces chemo-resistance and systemic toxicity. One way to circumvent development of resistant disease is to develop novel drugs that target normal cellular functions, which are over-expressed in the transformed phenotype. In our quest to characterize altered cellular pathways that are essential for the transformed phenotype, we have identified a member of a RNA helicase family, DDX3, which is dysregulated in many cancer types such as breast, brain, lung and leukemia. Although the biological functions of DDX3 are still under investigation, we have demonstrated that over-expression of DDX3 promotes epithelial-mesenchymal transition and down-regulates E-cadherin expression. In our efforts to abrogate DDX3 functions in vivo, we have designed a novel small molecule, RK-33 (diimidazodiazepine) that decreased DDX3 expression under both normoxic and hypoxic conditions. Functional analysis revealed that RK-33 was able to reduce lung tumor load in a transgenic mouse model of lung cancer. Moreover, in combination with radiation, there was a synergistic effect with respect to lung tumor reduction in the preclinical model. Similar results were obtained using a preclinical model of breast cancer. Importantly, RK-33 showed no toxicity in animals and thus we anticipate an expeditious translation of the preclinical data into the clinical setting.

Sept 20, 2010

History of FLT: The Long Path to PET
David Dick, PhD
MIPS Stanford

October 4, 2010

The Imaging Biomarker Ontology: ontology-based support for imaging biomarker research
Tiffany Ting Liu, Graduate Student in the Imaging Bioinformatics Lab (IBL)

October 25, 2010

Fluorine-18 PET-Tracer Development for Imaging Angiogenesis
Bin Shen, PhD, Radiochemistry Facility
Towards photoacoustic and ultrasound imaging of prostate
Sri Rajasekhar Kothapalli, PhD, Gambhir Lab

November 1, 2010

M114 ALWAY

Investigation into therapeutic potential of MicroRNA for cardiovascular disease
Shijun Hu, PhD, Wu Lab
Improved Protein Scaffolds for Molecular Imaging
Benjamin Hackel, PhD, Gambhir Lab

November 15, 2010

LUCAS LEARNING CENTER/P083 PET

Imaging of Tumor Neovascularization in a Transgenic Mouse Mode
Carsten Nielsen, PhD, Gambhir Lab
Novel probes for PET imaging of cystine transport
Aileen Hoehne, PhD, Gambhir Lab

November 29, 2010

Hypoxia in Models of Lung Cancer. Implications for Therapeutics Studies
Marta Vilalta Colomer, PhD, Graves Lab
Strategies for Potent and Specific Therapeutic Gene Therapy of Hepatocellular Carcinoma
John Ronald, PhD, Gambhir Lab

December 6, 2010

The State of Hypoxia PET Imaging at Stanford
Ted Graves, PhD
Assistant Professor, Department of Radiation Oncology

Sponsored by: Molecular Imaging Program at Stanford (MIPS) (mips.stanford.edu);
Host: Director, Sanjiv Sam Gambhir, MD, PhD (sgambhir@stanford.edu)

If you would like to be included on the MIPS email distribution list for weekly meeting reminders, contact Susan Singh.