Biology subjects

Kwon, Y. J.

Publications and source records attributed to Kwon, Y. J..

3 recordsLinked to original sources

bioRxiv2025

Multimodal gene and targeted drug therapy for chronic myelogenous leukemia: Computational target analysis and therapeutic validation

Developing an efficient and safe therapy necessitates a mechanistic understanding of the complex underlying pathology and manipulation of the multiple pathways at the molecular and genetic level. Network-based simulation of chronic myeloid leukemia (CML), a relatively well-understood cancer model, revealed the dynamics of simultaneously expressing pro-apoptotic BIM and silencing pro-survival MCL-1 in combination with the BCR-ABL-targeted tyrosine kinase inhibitor dasatinib. Viral/nonviral chimeric nanoparticles (ChNPs) composed of a BIM-expressing adeno-associated virus (AAV) core and a degradable polymeric shell that encapsulates MCL-1 siRNA (BIM/MCL-1 ChNPs) synergistically and selectively killed BCR-ABL+ CML cells in combination with dasatinib. In a mouse CML model, the BIM/MCL-1 ChNPs and dasatinib combination therapy suppressed proliferation of BCR-ABL+ hematopoietic cells and prevented leukemic infiltration of organs. The synergistic anti-leukemic effect was further pronounced in an acute phase model of the disease. This study investigated a strategy of developing a versatile and tunable multimodal therapy assisted by a computational toolset that analyzes the molecular foundation of a disease and predicts therapeutic response. The interdisciplinary approach developed and validated in this study can be used in discovering new therapies for cancer and other diseases. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/656072v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1e3632borg.highwire.dtl.DTLVardef@1839f12org.highwire.dtl.DTLVardef@4060c0org.highwire.dtl.DTLVardef@8ff0de_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstractC_FLOATNO summarizing the study design and approach. A schematic representation of the integrated in silico and in vivo pipeline utilized in the study. The workflow begins with in silico simulations, including Boolean network modeling and protein-protein interaction (PPI) network analyses, leading to target discovery, optimized nanoparticle design, and validation in pathological contexts. This was followed by therapeutic efficacy assessments of BIM/MCL-1 ChNPs and their combination with dasatinib in BCR-ABL+ leukemia models in vitro and in vivo. C_FIG

cancer biology↗

bioRxiv2019

Hepatocytic Prominin-1 protects liver fibrosis by stabilizing the SMAD7 protein

Background and AimsProminin-1 (PROM1) is known to be upregulated in hepatocytic progenitor cells (HPCs) and cholangiocytes of fibrotic livers. To understand the function of upregulated PROM1 during liver fibrosis, we analyzed liver fibrosis from global and liver-specific Prom1 knockout mice and investigated the molecular mechanism of how Prom1 protects the liver against liver fibrosis. MethodsWe analyzed PROM1 expression from human liver with mild and severe liver fibrosis (n=4-9). Liver fibrosis was induced by carbon tetrachloride (CCl4) treatment and bile duct ligation (BDL) from wild type and global and liver-specific knockout mice (n=3-13). The severity of liver fibrosis was determined by qRT-PCR, immunostaining and immunoblotting for fibrotic markers such as SMA, collagen. TGF{beta} signaling was also analyzed from fibrotic liver and primary hepatocytes of wild type and global and liver-specific knockout mice (n=3-5). Molecular interaction between PROM1 and SMAD7 was determined by endogenous and exogenous co-immunoprecipitation. ResultsPROM1 was found in the plasma membranes of both healthy and fibrotic hepatocytes and cholangiocytes. Global Prom1 knockout aggravated BDL- and CCl4-induced liver fibrosis. Prom1-/- hepatocytes showed increased TGF{beta} signaling due to reduced SMAD7 protein expression compared to that in wild-type hepatocytes. PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that liver-specific Prom 1 knockout aggravated BDL-induced liver fibrosis due to reduced levels of SMAD7. ConclusionHepatocytic PROM1 stabilizes SMAD7, preventing TGF{beta} signaling. Thus, PROM1 is necessary for the negative regulation of TGF{beta} signaling during liver fibrosis.

cell biology↗

bioRxiv2017

Classifying smartphone-based accelerometer data to obtain validated measures of subject activity status, step count, and gait speed

BackgroundThe ubiquitous spread of smartphone technology throughout global societies offers an unprecedented opportunity to ethically obtain long-term, highly accurate measurements of individual physical activity. For example, the smartphone intrinsic 3-D accelerometer can be queried during normal phone operation to save time series of acceleration magnitudes (in each of the component directions) for near-real time or post processing.\n\nObjectiveWe describe simple, straightforward algorithms (based on windowed Fourier analysis) for accelerometer data quality control and behavioral classification.\n\nMethodsTo maximize the clinical utility of our classifications, we focused on differentiating the following conditions: forgotten phone, subject resting, low physical activity, high physical activity. We further differentiated high physical activity into epochs of walking and climbing stairs, and further quantified walking to infer step count and gait speed.\n\nResultsWe validated these algorithms in 75 individuals, in both laboratory (treadmill) and naturalistic settings. Our algorithm performance was quite satisfactory, with accuracies of 92-99% for all behavioral categories, and 87-90% for gait metrics in naturalistic settings.\n\nConclusionsWe conclude that smartphones are valid and accurate platforms for measuring day-to-day physical activity in ambulatory, community dwelling individuals.

bioengineering↗