Clinical Research Laboratories

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.

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My research interests include the use of SPECT/CT, PET/MRI and PET/CT for early cancer detection;clinical translation of novel PET radiopharmaceuticals; peptide-based diagnostic imaging and therapy.

The series of scans in the collage won the Best Radiology Image in 2016 Minnies awards, recognizing excellence in radiology. The image examines two new PET radiotracers, 68Ga-PSMA11 and 68Ga-RM2, to determine their effectiveness in identifying rising levels of prostate-specific antigen (PSA), which signals prostate cancer recurrence. Since then, gallium-68 PSMA-11 was approved by the FDA while gallium-68 RM2 was further studied in a DoD sponsored Impact Award.

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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.

My clinical focus is on radiation management of head and neck cancer (HNC) and the application of novel therapies in HNC. I co-chair the NRG Oncology Group, which conducts large phase II-III trials to test new treatments in different cancer types. My lab works on approaches to regenerate salivary glands after radiation damage, identification of biomarkers of prognosis and treatment resistance in HNC, and development of novel treatment strategies for HNC. For therapy development, we are interested in developing novel nanoparticle-base approaches to down-regulate/ delete several genes including Galectin-1 in HNC, MIB-1/MIB-L1 in adenoid cystic carcinoma and degrade mutated NRF2/Keap1 proteins in HNC. We are also interested in evaluating novel theragnostic treatments for salivary gland cancers and develop ways to protect salivary glands from radionuclide therapy. Participation in MIPS would help to enhance our research direction toward developing novel theragnositcs for salivary gland malignancies.

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The lab focuses on expanding the capability of MR and PET/MR as it relates to applications in body imaging. This includes evaluating new MR sequences, contrast mechanisms, and contrast agents, as well as combining PET molecular imaging agents with MRI. Particular research focuses within body imaging include detection of cancer within the prostate, identifying metastatic disease involvement of lymph nodes, and MR protocol optimization for robustness and diagnostic capability.

My clinical and translational research has a strong molecular imaging emphasis. In particular, FDG-PET imaging biomarkers and their impact on response to radiation therapy both in terms of cancer control and normal tissue toxicity have been a longstanding part of my research and publication track record. I have also conducted prospective clinical trials of FLT-PET and EF5-PET. With the advent of the world’s first RefleXion PET-linac coming online in our department, my activity in PET guided radiation therapy will be increasing further.

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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.

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The research interest of the Mari Aparici Lab resides in translational Molecular Imaging from preclinical to bed side. We are particularly interested in the field of Theranostics, with a focus in the development and clinical translation of diagnostic and therapeutic pared molecular-probes that allow for specific internal radio-treatments at the cellular level. The goal is to bring to the clinical arena promising alpha and beta emitter-molecular probes that may allow for more precise, effective and efficient systemic therapies with maximum sparing of benign tissues and minimal side effects.

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Our research is focused on the study of the ontogeny and control of heme catabolism and bilirubin production in the developing neonate. A better understanding of the role of increased bilirubin production in neonatal jaundice and the prevention of hemolytic jaundice has remained an overall objective of our program. To this end, we are actively investigating a more targeted, preventive approach to the diagnosis and treatment of newborns, who are high producers of the pigment and/or unable to efficiently eliminate bilirubin, thus leading to an accumulation of the pigment in circulation and tissues, which may lead to irreversible neurologic injury. Control of bilirubin production is a logical strategy but has unexplored consequences for the immature mammal. Using murine models, we are studying the pivotal role of heme oxygenase (HO), the rate-limiting enzyme in the production of bilirubin, under a variety of commonly encountered pathological conditions, as well as in antioxidant defense, immune response and the regulation of hematopoiesis. In support of the above interests, we use transgenic mice created for optical imaging of gene expression. We continued to screen a variety of metalloporphyrins, inhibitors of HO, and other compounds for maximum in vitro and in vivo inhibitory efficacy with minimal side effects; to determine the ontogeny of the HO enzyme system in various murine tissues, focusing on perturbations resulting from treatment with HO inhibitors; and further to develop and test new technologies for noninvasive or minimally-invasive measurements of in vivo metabolism that could be used for diagnostic and monitoring purposes. We also study the causes of preterm birth and ways to prevent it. This work focuses on the innate and adaptive immune systems and cell signaling behaviors using a variety of optical reporting strategies, as well as “omics” measures.

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Dr. Nieman is a cardiologist and associate professor in the departments of Cardiovascular Medicine and Radiology. He investigates advanced cardiac imaging techniques, and current projects include the development and technical validation of functional CT applications for ischemic heart disease, and the clinical validation of cardiac CT in the form of clinical effectiveness trials.

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.

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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.

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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.

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