A5006825449- Cancer, Hypoxia, and Metabolism
- Medical Imaging Techniques and Applications
- Cancer Research and Treatments
- Virus-based gene therapy research
- bioluminescence and chemiluminescence research
- Cancer Immunotherapy and Biomarkers
- Mitochondrial Function and Pathology
- CAR-T cell therapy research
- Immune cells in cancer
- Glioma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Radiopharmaceutical Chemistry and Applications
- Nanoplatforms for cancer theranostics
- ATP Synthase and ATPases Research
- Neuroblastoma Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Cells and Metastasis
- Brain Metastases and Treatment
- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Advanced Fluorescence Microscopy Techniques
- Epigenetics and DNA Methylation
- Cancer, Lipids, and Metabolism
Cornell University
2012-2025
Weill Cornell Medicine
2021-2025
Presbyterian Hospital
2024
Memorial Sloan Kettering Cancer Center
2013-2023
Kettering University
2010-2022
Skolkovo Institute of Science and Technology
2019
Neurology, Inc
2006-2014
Memorial Hospital
2007-2013
Cyclotron (Netherlands)
2011
Rutgers, The State University of New Jersey
2011
We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual from a population established culture the pleural effusion patient showed distinct organ-specific metastasis. Single-cell progenies derived this exhibited markedly different abilities metastasize bone, lung, or adrenal medulla, which suggests that metastases organs have requirements. Transcriptomic profiling revealed these single-cell similarly express...
TGF-β can signal by means of Smad transcription factors, which are quintessential tumor suppressors that inhibit cell proliferation, and Smad-independent mechanisms, have been implicated in progression. Although mutations disable this tumor-suppressive pathway certain cancers, breast cancer cells frequently evade the cytostatic action while retaining function. Through immunohistochemical analysis human bone metastases functional imaging a mouse xenograft model, we provide evidence for active...
Tumor hypoxia is a spatially and temporally heterogeneous phenomenon, which results from several tumor host tissue-specific processes. To study the dynamics spatial heterogeneity of hypoxia-inducible factor-1 (HIF-1)-specific transcriptional activity in tumors, we used repetitive noninvasive positron emission tomography (PET) imaging hypoxia-induced HIF-1 tumors living mice. This approach uses novel retroviral vector bearing HIF-1-inducible "sensor" reporter gene (HSV1-tk/GFP fusion)...
Cancer cells adapt their metabolism during tumorigenesis. We studied two isogenic breast cancer lines (highly metastatic 4T1; nonmetastatic 67NR) to identify differences in glucose and glutamine response metabolic environmental stress. Dynamic magnetic resonance spectroscopy of 13C-isotopomers showed that 4T1 have higher glycolytic tricarboxylic acid (TCA) cycle flux than 67NR readily switch between glycolysis oxidative phosphorylation (OXPHOS) different extracellular environments. OXPHOS...
Abstract Purpose: To investigate the relationship between lactate dehydrogenase A (LDH-A) expression, concentration, cell metabolism, and metastases in murine 4T1 breast tumors. Experimental Design: Inhibition of LDH-A expression protein levels were achieved a metastatic cancer line (4T1) using short hairpin RNA (shRNA) technology. The tumor concentration (measured by magnetic resonance spectroscopic imaging, MRSI) was assessed. Results: knockdown cells (KD9) showed significant reduction LDH...
Previous studies show that LDH-A knockdown reduces orthotopic 4T1 breast tumor lactate and delays growth the development of metastases in nude mice. Here, we report significant changes microenvironment (TME) a more robust anti-tumor response immune competent BALB/c murine cancer cells were transfected with shRNA plasmids directed against (KD) or scrambled control plasmid (NC). Cells also transduced dual luciferase-based reporter systems to monitor HIF-1 activity by bioluminescence imaging,...
HIF-1alpha is overexpressed in many human cancers compared to normal tissues due the interaction of a multiplicity factors and pathways that reflect specific genetic alterations extracellular stimuli. We developed two chimeric reporter systems, HIF-1alpha/FLuc HIF-1alpha(DeltaODDD)/FLuc, investigate tightly controlled level protein (NIH3T3 HEK293) glioma (U87) cells. These systems provided an opportunity degradation different cell lines, both culture xenografts. Using immunofluorescence...
Abstract Purpose: We compared the metabolic profiles and association between LDH-A expression lactate production in two isogenic murine breast cancer cell lines tumors (67NR 4T1). These were derived from a single mammary tumor have different growth phenotypes. Experimental Design: expression, concentration, glucose utilization, oxygen consumption measured cells, potential relationship levels [measured by magnetic resonance spectroscopic imaging (MRSI)] utilization...
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success not been observed solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR cells expressing Click Beetle Red luciferase reporter) were used to study hPSMA targeting assess trafficking persistence by bioluminescence imaging (BLI). We investigated antitumor efficacy prostate-specific membrane (hPSMA), presence...
Monitoring genetically altered T cells is an important component of adoptive cell therapy in patients, and the ability to visualize their trafficking/targeting, proliferation/expansion, retention/death using highly sensitive reporter systems that do not induce immunologic response would provide useful information. Therefore, we focused on human gene have potential for translation clinical studies. The objective vivo imaging studies was determine minimum number could be visualized with...
Tumor reliance on glycolysis is a hallmark of cancer. Immunotherapy more effective in controlling glycolysis-low tumors lacking lactate dehydrogenase (LDH) due to reduced tumor efflux and enhanced glucose availability within the microenvironment (TME). LDH inhibitors (LDHi) reduce uptake growth preclinical models, but their impact tumor-infiltrating T cells not fully elucidated. have higher basal expression levels compared with infiltrating cells, creating therapeutic opportunity for...
We used bioluminescence imaging to reveal patterns of metastasis formation by human breast cancer cells in immunodeficient mice. Individual from a population established culture the pleural effusion patient showed distinct organ-specific metastasis. Single-cell progenies derived this exhibited markedly different abilities metastasize bone, lung, or adrenal medulla, which suggests that metastases organs have requirements. Transcriptomic profiling revealed these single-cell similarly express...
Metastasis is a multistep and multifunctional biological cascade that the final most life-threatening stage of cancer progression. Understanding underpinnings this complex process extreme clinical relevance requires unbiased comprehensive scrutiny. In recent years, we have utilized xenograft model breast metastasis to discover genes mediate organ-specific patterns metastatic colonization. Examination transcriptomic data from cohorts primary cancers revealed subset site-specific are selected...
A human-derived intrinsically nonimmunogenic reporter gene was tested for PET imaging of different molecular-genetic processes potential clinical use.The human mitochondrial thymidine kinase type 2 (hTK2) truncated at the N terminus (DeltahTK2), alone or fused with green fluorescent protein (GFP), used preclinical evaluation in a mouse model. The levels enzymatic activity DeltahTK2 and GFP proteins were assessed using radiotracer accumulation prodrug activation assays vitro subcutaneous...
The norepinephrine transporter (NET) has recently been suggested as a useful reporter gene. We have extended this effort by constructing an internal ribosomal entry site (IRES)-linked hNET-green fluorescent protein (GFP) hybrid gene for both nuclear and optical imaging. <b>Methods:</b> A retroviral vector pQCXhNET-IRES-GFP was constructed used to generate several cell lines xenografts. Transduced cells were sorted fluorescence-activated sorting based on GFP expression in vitro vivo imaging...
The human somatostatin receptor subtype 2 (hSSTr2)-68Ga-DOTATOC reporter system has several attractive features for potential translation to studies. These include a low expression of hSSTr2 in most organs, rapid internalized accumulation 68Ga-DOTATOC the SSTr2-expressing cells, and excretion unbound radioligand by renal system. We performed series vitro vivo validation studies this system.A retroviral vector containing dual reporter, pQCXhSSTr2-IRES-GFP (IRES: internal ribosome entry site;...
Significance Solid tumors adapt a glycolytic phenotype for their energetic requirements, leading to acidification of the extracellular environment. Targeting this global event is important gauge pace tumor growth and invasiveness, as well provide basis predicting disease response pH-dependent chemotherapies. To realize goal, noninvasive method necessary measure meet clinical needs. This study explores utility pH (low) insertion peptide, an acidosis-targeting PET-based imaging probe...