Person:
Lee, Hakho

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Lee

First Name

Hakho

Name

Lee, Hakho
Author's Publications: search.filters.isAuthorOfPublication.382a223a-f481-4666-a680-89aadcc1e3a4

Search Results

Now showing 1 - 10 of 14
  • Thumbnail Image
    Publication
    Rapid identification of health care–associated infections with an integrated fluorescence anisotropy system
    (American Association for the Advancement of Science, 2016) Park, Ki Soo; Huang, Chen-Han; Lee, Kyungheon; Yoo, Yeong-Eun; Castro, Cesar; Weissleder, Ralph; Lee, Hakho
    Health care–associated infections (HAIs) and drug-resistant pathogens have become a major health care issue with millions of reported cases every year. Advanced diagnostics would allow clinicians to more quickly determine the most effective treatment, reduce the nonspecific use of broad-spectrum antimicrobials, and facilitate enrollment in new antibiotic treatments. We present a new integrated system, polarization anisotropy diagnostics (PAD), for rapid detection of HAI pathogens. The PAD uses changes of fluorescence anisotropy when detection probes recognize target bacterial nucleic acids. The technology is inherently robust against environmental noise and economically scalable for parallel measurements. The assay is fast (2 hours) and performed on-site in a single-tube format. When applied to clinical samples obtained from interventional procedures, the PAD determined the overall bacterial burden, differentiated HAI bacterial species, and identified drug resistance and virulence status. The PAD system holds promise as a powerful tool for near-patient, rapid HAI testing.
  • Thumbnail Image
    Publication
    Nanoparticle Detection of Urinary Markers for Point-of-Care Diagnosis of Kidney Injury
    (Public Library of Science, 2015) Chung, Hyun Jung; Pellegrini, Kathryn L.; Chung, Jaehoon; Wanigasuriya, Kamani; Jayawardene, Innocent; Lee, Kyungheon; Lee, Hakho; Vaidya, Vishal; Weissleder, Ralph
    The high incidence of acute and chronic kidney injury due to various environmental factors such as heavy metals or chemicals has been a major problem in developing countries. However, the diagnosis of kidney injury in these areas can be more challenging due to the lack of highly sensitive and specific techniques that can be applied in point-of-care settings. To address this, we have developed a technique called ‘micro-urine nanoparticle detection (μUNPD)’, that allows the detection of trace amounts of molecular markers in urine. Specifically, this technique utilizes an automated on-chip assay followed by detection with a hand-held device for the read-out. Using the μUNPD technology, the kidney injury markers KIM-1 and Cystatin C were detected down to concentrations of 0.1 ng/ml and 20 ng/ml respectively, which meets the cut-off range required to identify patients with acute or chronic kidney injury. Thus, we show that the μUNPD technology enables point of care and non-invasive detection of kidney injury, and has potential for applications in diagnosing kidney injury with high sensitivity in resource-limited settings.
  • Thumbnail Image
    Publication
    Holographic Assessment of Lymphoma Tissue (HALT) for Global Oncology Field Applications
    (Ivyspring International Publisher, 2016) Pathania, Divya; Im, Hyungsoon; Kilcoyne, Aoife; Sohani, Aliyah R.; Fexon, Lioubov; Pivovarov, Misha; Abramson, Jeremy; Randall, Thomas; Chabner, Bruce; Weissleder, Ralph; Lee, Hakho; Castro, Cesar
    Low-cost, rapid and accurate detection technologies are key requisites to cope with the growing global cancer challenges. The need is particularly pronounced in resource-limited settings where treatment opportunities are often missed due to the absence of timely diagnoses. We herein describe a Holographic Assessment of Lymphoma Tissue (HALT) system that adopts a smartphone as the basis for molecular cancer diagnostics. The system detects malignant lymphoma cells labeled with marker-specific microbeads that produce unique holographic signatures. Importantly, we optimized HALT to detect lymphomas in fine-needle aspirates from superficial lymph nodes, procedures that align with the minimally invasive biopsy needs of resource-constrained regions. We equipped the platform to directly address the practical needs of employing novel technologies for “real world” use. The HALT assay generated readouts in <1.5 h and demonstrated good agreement with standard cytology and surgical pathology.
  • Thumbnail Image
    Publication
    Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma
    (Nature Pub. Group, 2015) Shao, Huilin; Chung, Jaehoon; Lee, Kyungheon; Balaj, Leonora; Min, Changwook; Carter, Bob S.; Hochberg, Fred H.; Breakefield, Xandra; Lee, Hakho; Weissleder, Ralph
    Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumours is often not a clinical option. MGMT (O6-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult, and, when done, primarily relies on promoter methylation studies of tumour biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients.
  • Thumbnail Image
    Publication
    On Chip Analysis of CNS Lymphoma in Cerebrospinal Fluid
    (Ivyspring International Publisher, 2015) Turetsky, Anna; Lee, Kyungheon; Song, Jun; Giedt, Randy; Kim, Eunha; Kovach, Alexandra E.; Hochberg, Ephraim; Castro, Cesar; Lee, Hakho; Weissleder, Ralph
    Molecular profiling of central nervous system lymphomas in cerebrospinal fluid (CSF) samples can be challenging due to the paucicellular and limited nature of the samples. Presented herein is a microfluidic platform for complete CSF lymphoid cell analysis, including single cell capture in sub-nanoliter traps, and molecular and chemotherapeutic response profiling via on-chip imaging, all in less than one hour. The system can detect scant lymphoma cells and quantitate their kappa/lambda immunoglobulin light chain restriction patterns. The approach can be further customized for measurement of additional biomarkers, such as those for differential diagnosis of lymphoma subtypes or for prognosis, as well as for imaging exposure to experimental drugs.
  • Thumbnail Image
    Publication
    Real-time quantitative analysis of metabolic flux in live cells using a hyperpolarized micromagnetic resonance spectrometer
    (American Association for the Advancement of Science, 2017) Jeong, Sangmoo; Eskandari, Roozbeh; Park, Sun Mi; Alvarez, Julio; Tee, Sui Seng; Weissleder, Ralph; Kharas, Michael G.; Lee, Hakho; Keshari, Kayvan R.
    Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or “fluxes” of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials. However, because of their limited sensitivity, these methods require a larger number of cells, on the order of 107, which is impractical for analyzing scant target cells or mass-limited samples. We present a new technology platform, a hyperpolarized micromagnetic resonance spectrometer (HMRS), that achieves real-time, 103-fold more sensitive metabolic analysis on live cells. This platform enables quantification of the metabolic flux in a wide range of cell types, including leukemia stem cells, without significant changes in viability, which allows downstream molecular analyses in tandem. It also enables rapid assessment of metabolic changes by a given drug, which may direct therapeutic choices in patients. We further advanced this platform for high-throughput analysis of hyperpolarized molecules by integrating a three-dimensionally printed microfluidic system. The HMRS platform holds promise as a sensitive method for studying metabolic dynamics in mass-limited samples, including primary cancer cells, providing novel therapeutic targets and an enhanced understanding of cellular metabolism.
  • Thumbnail Image
    Publication
    MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer
    (Elsevier, 2017) Godlewski, Jakub; Ferrer-Luna, Ruben; Rooj, Arun; Mineo, Marco; Ricklefs, Franz; Takeda, Yuji S.; Nowicki, M. Oskar; Salińska, Elżbieta; Nakano, Ichiro; Lee, Hakho; Weissleder, Ralph; Beroukhim, Rameen; Chiocca, E.; Bronisz, Agnieszka
    Summary Despite the importance of molecular subtype classification of glioblastoma (GBM), the extent of extracellular vesicle (EV)-driven molecular and phenotypic reprogramming remains poorly understood. To reveal complex subpopulation dynamics within the heterogeneous intratumoral ecosystem, we characterized microRNA expression and secretion in phenotypically diverse subpopulations of patient-derived GBM stem-like cells (GSCs). As EVs and microRNAs convey information that rearranges the molecular landscape in a cell type-specific manner, we argue that intratumoral exchange of microRNA augments the heterogeneity of GSC that is reflected in highly heterogeneous profile of microRNA expression in GBM subtypes.
  • Thumbnail Image
    Publication
    Sparsity-Based Pixel Super Resolution for Lens-Free Digital In-line Holography
    (Nature Publishing Group, 2016) Song, Jun; Leon Swisher, Christine; Im, Hyungsoon; Jeong, Sangmoo; Pathania, Divya; Iwamoto, Yoshiko; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho
    Lens-free digital in-line holography (LDIH) is a promising technology for portable, wide field-of-view imaging. Its resolution, however, is limited by the inherent pixel size of an imaging device. Here we present a new computational approach to achieve sub-pixel resolution for LDIH. The developed method is a sparsity-based reconstruction with the capability to handle the non-linear nature of LDIH. We systematically characterized the algorithm through simulation and LDIH imaging studies. The method achieved the spatial resolution down to one-third of the pixel size, while requiring only single-frame imaging without any hardware modifications. This new approach can be used as a general framework to enhance the resolution in nonlinear holographic systems.
  • Thumbnail Image
    Publication
    Highly sensitive detection of protein biomarkers via nuclear magnetic resonance biosensor with magnetically engineered nanoferrite particles
    (Dove Medical Press, 2016) Jeun, Minhong; Park, Sungwook; Lee, Hakho; Lee, Kwan Hyi
    Magnetic-based biosensors are attractive for on-site detection of biomarkers due to the low magnetic susceptibility of biological samples. Here, we report a highly sensitive magnetic-based biosensing system that is composed of a miniaturized nuclear magnetic resonance (NMR) device and magnetically engineered nanoferrite particles (NFPs). The sensing performance, also identified as the transverse relaxation (R2) rate, of the NMR device is directly related to the magnetic properties of the NFPs. Therefore, we developed magnetically engineered NFPs (MnMg-NFP) and used them as NMR agents to exhibit a significantly improved R2 rate. The magnetization of the MnMg-NFPs was increased by controlling the Mn and Mg cation concentration and distribution during the synthesis process. This modification of the Mn and Mg cation directly contributed to improving the R2 rate. The miniaturized NMR system, combined with the magnetically engineered MnMg-NFPs, successfully detected a small amount of infectious influenza A H1N1 nucleoprotein with high sensitivity and stability.
  • Thumbnail Image
    Publication
    A magneto-DNA nanoparticle system for the rapid and sensitive diagnosis of enteric fever
    (Nature Publishing Group, 2016) Park, Ki Soo; Chung, Hyun Jung; Khanam, Farhana; Lee, Hakho; Rashu, Rasheduzzaman; Bhuiyan, Md. Taufiqur; Berger, Amanda; Harris, Jason; Calderwood, Stephen; Ryan, Edward; Qadri, Firdausi; Weissleder, Ralph; Charles, Richelle
    There is currently no widely available optimal assay for diagnosing patients with enteric fever. Here we present a novel assay designed to detect amplified Salmonella nucleic acid (mRNA) using magneto-DNA probes and a miniaturized nuclear magnetic resonance device. We designed primers for genes specific to S. Typhi, S. Paratyphi A, and genes conserved among Salmonella enterica spp. and utilized strongly magnetized nanoparticles to enhance the detection signal. Blood samples spiked with in vitro grown S. Typhi, S. Paratyphi A, S. Typhimurium, and E. coli were used to confirm the specificity of each probe-set, and serial 10-fold dilutions were used to determine the limit of the detection of the assay, 0.01–1.0 CFU/ml. For proof of principle, we applied our assay to 0.5 mL blood samples from 5 patients with culture-confirmed enteric fever from Bangladesh in comparison to 3 healthy controls. We were able to detect amplified target cDNA in all 5 cases of enteric fever; no detectable signal was seen in the healthy controls. Our results suggest that a magneto-DNA nanoparticle system, with an assay time from blood collection of 3.5 hours, may be a promising platform for the rapid and culture-free diagnosis of enteric fever and non-typhoidal Salmonella bacteremia.