This lab employs model systems whereby we can conditionally regulate oncogene expression in human or mouse cells in vitro or in mice. We incorporate state-of-the-art methods of molecular imaging, and computational analysis to examine and model tumorigenesis.
We have a particular focus on examining when and how oncogene inactivation can be used to treat human cancer. Our work has uncovered the notion that tumors can be "oncogene addicted".
We have shown that oncogene addiction involves both tumor intrinsic as well as host (immune) dependent mechanisms. We examine three questions:
How does oncogene activation cause cancer?
How and when does oncogene inactivation cause cancer to regress?
How can we predict when oncogene inactivation will cure cancer?
Dr. Wu received his MD from Yale University School of Medicine. He trained in internal medicine and cardiology at UCLA followed by a PhD in the Department of Molecular and Medical Pharmacology. His clinical interests involve cardiovascular imaging and adult congenital heart disease. Dr. Wu has published >300 manuscripts. His lab works on biological mechanisms of patient-specific and disease-specific induced pluripotent stem cells (iPSCs). The main goals are for (i) understanding basic cardiovascular disease mechanisms, (ii) accelerate drug discovery and screening, and (iii) develop personalized medicine and ìclinical trial in a dishî platforms. His lab uses a combination of genomics, stem cells, cellular & molecular biology, physiological testing, and molecular imaging technologies to better understand molecular and pathophysiological processes.
This laboratory is currently focusing on three major areas of research: 1) rapid detection and imaging of bacterial infection, especially antibiotics-resistant bacteria and mycobacterium tuberculosis (MTB), 2) understanding and imaging tumor response to treatment, and 3) imaging-guided tumor resection. Towards these goals, we are developing new molecular probes and imaging strategies to image and interrogate a broad range of molecular targets, from enzymes like hydrolases (beta-lactamases), proteases (such as caspases and MMPs), DNA polymerases (PARP-1), to reactive oxygen species (ROS). We also exploring nanoparticles and developing nanotechnologies in order to improve the sensitivity and specificity of detection and imaging. Through innovation in probe chemistry and nanotechnology, we strive to provide new solutions to these important problems in global health, cancer biology and therapy.
Developing novel imaging assays for studying cellular signal transduction networks in living animals;
Imaging the role of epigenetic histone methylation in the pathogenesis and therapeutic interventions of cancers;
Ultrasound-microbubble mediated imaging of guided targeted drug and antisense-microRNAs delivery that functionally alters cellular homeostasis, thereby enhancing response to chemotherapy for clinically difficult aggressive and metastatic triple negative breast cancer (TNBC), and for advanced hepatocellular carcinoma;
Understanding the role of cancers antioxidant chemopreventive mechanism to improve therapeutic efficiency by overcoming the drug resistance facilitated by Nrf2-mediated phase II enzymes;
Developing multifunctional gene therapy system to improve TNBC therapy.
This laboratory is focused on image instrumentation, X-ray molecular imaging, image reconstruction, image processing, radiation therapy treatment planning, and image guided intervention. The group is developing novel solutions to advance various clinical imaging modalities such as CT, cone beam CT (CBCT), MRI, and PET, and investigating new strategies for molecular imaging and molecular image-guided therapeutics and treatment response assessment. We are also working on applications of big data in radiation oncology and data-driven image analysis and treatment planning techniques.
This laboratory effort focuses on development and clinical translation of technologies that will improve the success of surgeons to efficiently remove cancer with negative margins. The lab focuses on integrating novel optical dye technology, open field and closed system optical imaging hardware systems, and new probe development to allow for safe and successful translation to the operating room and pathology suite. We are investigating the utility of fluorescently labeled therapeutic antibodies to image subclinical disease in real time during surgery resections in a range of cancer types including head and neck, brain, and pancreatic cancer.Furthermore, we exploring barriers to drug delivery and molecular imaging of tumor response during targeted therapy in preclinical and clinical studies.
This laboratory is focused on understanding tumor and normal tissue radiation response through the development and application of molecular imaging techniques. This goal is pursued through work spanning technique development, basic research, and clinical translation. We are a multi-disciplinary group with expertise in engineering, biology, chemistry, medicine, and computer science, and have developed a variety of methods of noninvasively detecting and quantifying molecular and physiologic aspects of radiation and tumor biology, including oxygen concentrations, hypoxia-regulated gene expression, metabolism, and cell migration. In addition, in order to evaluate the relevance of these molecular factors to clinical radiation therapy, we have developed a system for the delivery of clinically-similar image-guided conformal radiotherapy to small animals. This myriad of tools is being applied to elucidate the molecular, cellular, and clinical consequences of radiation exposure and cancer therapy.
We are currently investigating the developmental programming of beta cells within pancreatic islets to understand the fetal origins of diabetes and the intrauterine programming of these cells using novel anatomical and functional imaging techniques. As the physiology and associated pathology of islets are better understood, we hope to be able to translate our basic science findings into the clinical setting in relation to beta cell transplantation using minimally invasive techniques with image guidance.
The second arm of our research is on pancreatic cancer, especially with respect to developing and translating novel molecular guided therapies using minimally invasive image-guided techniques. One area which we are focusing on is the development of new nanoparticle platforms, for both imaging and therapy, and the delivery of these platforms into different experimental models of pancreatic cancer.
The Thakor Lab is also interested in developing and translating new bio-sensing technologies which can offer "Precision Medicine" to both pediatric and adult patients.
We focus on molecular and translational imaging of the brain especially in neuro-oncology. We develop novel experimental and molecular imaging techniques for theranostic applications in glioblastoma, both to interrogate fundamental biological events, and to use in new anticancer therapeutic strategies. Generally, this includes the in vivo imaging of gene expression and protein-protein interactions using reporter assays, as well as cellular and nano-imaging. Other emerging research interests include new glioma radiotracer development, studying the p53 transcriptional network in glioblastoma, imaging protein folding and misfolding in cancer, and developing novel nanoparticle-based drug and microRNA formulations for ultra-targeted treatments in endovascular neuro-oncology applications.
The mission of this laboratory is to understand both the mechanisms of disease (cancer, infection and genetic diseases), and the complex genetic programs of mammalian development and stem cell biology. We monitor these processes noninvasively as they occur in living animals. The methods developed and used by our group can simultaneously reveal the nuances and the overall picture of cellular and molecular processes in animal models. Using these approaches, we can rapidly assess the effects of antineoplastic therapies, antibiotics or antiviral drugs, revealing possible modes of action. These strategies result in significantly more information than can be obtained using a vivisectionist approach in that the animals are living and the data is obtained in real-time. One of our scientific goals is to develop tools that make the body essentially transparent for scientific discovery, and to use these tools to understand how pathogens cause disease and how the host organism responds to these pathogens, as well as how the immune system monitors cell transformation in cancer, and the regulatory networks that control cell migration and development.
This laboratory is interested in the development of novel instrumentation and software algorithms for in vivo imaging of molecular signals in humans and small laboratory animals. The goals of the instrumentation projects are to push the sensitivity and spatial, spectral, and/or temporal resolutions as far as physically possible. The algorithm goals are to understand the physical system comprising the subject tissues, radiation transport, and imaging system, and to provide the best available image quality and quantitative accuracy. The work involves computer modeling, position sensitive sensors, readout electronics, data acquisition, image formation, image processing, and data/image analysis algorithms, and incorporating these innovations into practical imaging devices. The ultimate goal is to introduce these new imaging tools into studies of molecular mecha- nisms and treatments of disease within living subjects.
This laboratory is interested in the development of multimodality molecular imaging techniques to study nociception and inflammation. In conjunction with a number of collaborators from a variety of disciplines, methods are being developed to look at the contributions from neurons and monocytic derivatives, both centrally and peripherally. Probes are currently being developed to look at voltage gated-ion channels, metabolic changes, macrophages/microglial cells, and, in the future, a variety of other related targets.
My laboratory is developing imaging assays to monitor fundamental cellular/molecular events in living subjects including patients. Technologies such as positron emission tomography (PET), optical (fluorescence, bioluminescence, Raman), ultrasound, and photoacoustic imaging are all under active investigation.
Imaging agents for multiple modalities including small molecules, engineered proteins, and nanoparticles are under development and being clinically translated. Our goals are to detect cancer early and to better manage cancer through the use of both in vitro diagnostics and molecular imaging. Strategies are being tested in small animal models and are also being clinically translated.
The use of annexin V, a phosphatidylserine binding protein, to reverse tumor immunosuppression in models of breast cancer.
The study of bacteriophage imaging and therapy of pseudomonas acute/chronic pulmonary infections in mice.
The use of Tc99m-HMPAO SPECT (a marker of intracellular glutathione) as an imaging biomarker of inherited and acquired mitochondrial disease in the brain and other mitochondrial rich organs in children and adults.
Application of bioinformatics / FTIR microspectroscopy in collaboration with Lawrence Berkeley National Laboratory Advance Light Source Division to study oxidative stress in live single cell fibroblasts and derived neurons from patients with inherited mitochondrial disease.
Our NIH-funded team of basic science researchers and physician scientists develops novel imaging solutions for pediatric patients with the goal to tackle significant problems encountered in clinical practice. We have extensive expertise in pre-clinical development and clinical translation of novel imaging technologies at the intersection of cell biology, nanomedicine and medical imaging: We developed “one stop” imaging tests for pediatric cancer staging, theranostic nanoparticles for cancer therapy without side effects, and patented techniques for stem cell tracking in patients. We recently initiated a collaborative program with 20 faculty from 9 Departments, who develop an imaging test for prediction and early treatment of tissue injuries after chemotherapy (PREDICT). Over the past 10 years, our team members received 77 honors and awards.
Our clinical research in Medical Oncology is an integrated program that leverages the scientific and clinical expertise at Stanford. Phase I trials sit at the interface of laboratory advances and later stage clinical development; expedite development of new treatments while ensuring patient safety; and provide the basis to prioritize resource allocation and inform rational drug development strategies. The program conducts trials that provide proof of mechanism, proof of principle, and proof of concept early in the process of developing novel therapeutics. One of our research interests is to use imaging to evaluate drug pharmacokinetics and target modulation.
The goal of the Radiation Biophysics laboratory to create entirely new technologies that address unanswered needs in the lab or the clinic. Our major focus is on ionizing radiation and how it can be used for imaging and therapeutic applications. Combining a variety of physical approaches such as biomedical optics, radiation sensing, computing, nanotechnology, and microfabrication, our work spans a wide breadth of application, from answering biological questions at the single cell level to improving the accuracy of radiation treatments. The lab is part of the Medical Physics division, in Radiation Oncology.
Interests involve novel MR research for a new thinking in the diagnosis of disease. MRI of tissue water is best depiction of disease; mapping brain water diffusion has revolutionized our knowledge of the onset and evolution of cerebral stroke, making the MR scanner the Gold Standard eyes and ears of choice for early and effective treatment of a variety of vascular diseases, trauma, cognition, and brain organization. MR tissue oxygenation allows us to ascertain oxygen utilization and metabolism. Up-to-date functional mapping can monitor neural networks while they work. Even minute physiological motions can be amplified with MR for a critical look at cellular density, pressures, and motions.
This laboratory focuses on the development and clinical translation of novel molecular and functional imaging biomarkers with special focus on imaging abdominal and pelvic cancer including pancreatic, liver, renal, ovarian, and prostate cancer. We further advance clinically available radiological imaging modalities such as ultrasound, magnetic resonance imaging (MRI), and positron emission tomography (PET) as promising imaging tools for early detection and treatment monitoring of abdominal and pelvic cancer. Our mission is to integrate novel molecular and functional imaging strategies into clinical protocols for improved patient care in the near future.
This laboratory focuses on advancing radiopharmaceutical sciences for the expanding field of molecular imaging. We design and synthesize novel radioligands/radiotracers that bind to molecular targets related to specific nervous system (central and peripheral) disorders and cancer biology. In addition, new radiolabeling techniques and methodologies will be created in our lab for emerging radiopharmaceutical development as well as for the general radiochemistry community. These radiochemistry approaches will be coupled with innovative chemical engineering to further investigate new molecular imaging strategies. Successful imaging agents will also be extended towards future human clinical applications.