IU Indianapolis ScholarWorks :: Browsing by Author "He, Xiaoming"

Browsing by Author "He, Xiaoming"

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Adaptive Kriging Method for Uncertainty Quantification of the Photoelectron Sheath and Dust Levitation on the Lunar Surface
(ASME, 2021) Wei, Xinpeng; Zhao, Jianxun; He, Xiaoming; Hu, Zhen; Du, Xiaoping; Han, Daoru; Mechanical and Energy Engineering, School of Engineering and Technology
This paper presents an adaptive Kriging based method to perform uncertainty quantification (UQ) of the photoelectron sheath and dust levitation on the lunar surface. The objective of this study is to identify the upper and lower bounds of the electric potential and that of dust levitation height, given the intervals of model parameters in the one-dimensional (1D) photoelectron sheath model. To improve the calculation efficiency, we employ the widely used adaptive Kriging method (AKM). A task-oriented learning function and a stopping criterion are developed to train the Kriging model and customize the AKM. Experiment analysis shows that the proposed AKM is both accurate and efficient.
Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation
(The American Society for Clinical Investigation, 2021-05-17) Xu, Hanchen; Van der Jeught, Kevin; Zhou, Zhuolong; Zhang, Lu; Yu, Tao; Sun, Yifan; Li, Yujing; Wan, Changlin; So, Ka Man; Liu, Degang; Frieden, Michael; Fang, Yuanzhang; Mosley, Amber L.; He, Xiaoming; Zhang, Xinna; Sandusky, George E.; Liu, Yunlong; Meroueh, Samy O.; Zhang, Chi; Wijeratne, Aruna B.; Huang, Cheng; Ji, Guang; Lu, Xiongbin; Medical and Molecular Genetics, School of Medicine
One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.
Bioinspired One Cell Culture Isolates Highly Tumorigenic and Metastatic Cancer Stem Cells Capable of Multilineage Differentiation
(Wiley, 2020-04-28) Wang, Hai; Agarwal, Pranay; Jiang, Bin; Stewart, Samantha; Liu, Xuanyou; Liang, Yutong; Hancioglu, Baris; Webb, Amy; Fisher, John P.; Liu, Zhenguo; Lu, Xiongbin; Tkaczuk, Katherine H. R.; He, Xiaoming; Medical and Molecular Genetics, School of Medicine
Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance
(Springer Nature, 2021-01-12) Wang, Hai; Liang, Yutong; Yin, Yue; Zhang, Jie; Su, Wen; White, Alisa M.; Jiang, Bin; Xu, Jiangsheng; Zhang, Yuntian; Stewart, Samantha; Lu, Xiaongbin; He, Xiaoming; Medical and Molecular Genetics, School of Medicine
The transmembrane P-glycoprotein (P-gp) pumps that efflux drugs are a major mechanism of cancer drug resistance. They are also important in protecting normal tissue cells from poisonous xenobiotics and endogenous metabolites. Here, we report a fucoidan-decorated silica-carbon nano-onion (FSCNO) hybrid nanoparticle that targets tumor vasculature to specifically release P-gp inhibitor and anticancer drug into tumor cells. The tumor vasculature targeting capability of the nanoparticle is demonstrated using multiple models. Moreover, we reveal the superior light absorption property of nano-onion in the near infrared region (NIR), which enables triggered drug release from the nanoparticle at a low NIR power. The released inhibitor selectively binds to P-gp pumps and disables their function, which improves the bioavailability of anticancer drug inside the cells. Furthermore, free P-gp inhibitor significantly increases the systemic toxicity of a chemotherapy drug, which can be resolved by delivering them with FSCNO nanoparticles in combination with a short low-power NIR laser irradiation.
Correction to Overcoming Ovarian Cancer Drug Resistance with a Cold Responsive Nanomaterial
(American Chemical Society, 2021) Wang, Hai; Agarwal, Pranay; Zhao, Gang; Ji, Guang; Jewell, Christopher M.; Fisher, John P.; Lu, Xiongbin; He, Xiaoming; Medicine, School of Medicine
[This corrects the article DOI: 10.1021/acscentsci.8b00050.].
Creating a capture zone in microfluidic flow greatly enhances the throughput and efficiency of cancer detection
(Elsevier, 2019-03) Sun, Mingrui; Xu, Jiangsheng; Shamul, James G.; Lu, Xiongbin; Husain, Syed; He, Xiaoming; Medical and Molecular Genetics, School of Medicine
Efficient capture of rare circulating tumor cells (CTCs) from blood samples is valuable for early cancer detection to improve the management of cancer. In this work, we developed a highly efficient microfluidics-based method for detecting CTCs in human blood. This is achieved by creating separate capture and flow zones in the microfluidic device (ZonesChip) and using patterned dielectrophoretic force to direct cells from the flow zone into the capture zone. This separation of the capture and flow zones minimizes the negative impact of high flow speed (and thus high throughput) and force in the flow zone on the capture efficiency, overcoming a major bottleneck of contemporary microfluidic approaches using overlapping flow and capture zones for CTC detection. When the flow speed is high (≥0.58 mm/s) in the flow zone, the separation of capture and flow zones in our ZonesChip could improve the capture efficiency from ∼0% (for conventional device without separating the two zones) to ∼100%. Our ZonesChip shows great promise as an effective platform for the detection of CTCs in blood from patients with early/localized-stage colorectal tumors.
Enhanced cancer therapy with cold-controlled drug release and photothermal warming enabled by one nanoplatform
(Elsevier, 2018-10) Wang, Hai; Agarwal, Pranay; Liang, Yutong; Xu, Jiangsheng; Zhao, Gang; Tkaczuk, Katherine H. R.; Lu, Xiongbin; He, Xiaoming; Medical and Molecular Genetics, School of Medicine
Stimuli-responsive nanoparticles hold great promise for drug delivery to improve the safety and efficacy of cancer therapy. One of the most investigated stimuli-responsive strategies is to induce drug release by heating with laser, ultrasound, or electromagnetic field. More recently, cryosurgery (also called cryotherapy and cryoablation), destruction of diseased tissues by first cooling/freezing and then warming back, has been used to treat various diseases including cancer in the clinic. Here we developed a cold-responsive nanoparticle for controlled drug release as a result of the irreversible disassembly of the nanoparticle when cooled to below ∼10 °C. Furthermore, this nanoparticle can be used to generate localized heating under near infrared (NIR) laser irradiation, which can facilitate the warming process after cooling/freezing during cryosurgery. Indeed, the combination of this cold-responsive nanoparticle with ice cooling and NIR laser irradiation can greatly augment cancer destruction both in vitro and in vivo with no evident systemic toxicity.
Heterozygous deletion of chromosome 17p renders prostate cancer vulnerable to inhibition of RNA polymerase II
(Springer Nature, 2018-10-22) Li, Yujing; Liu, Yunhua; Xu, Hanchen; Jiang, Guanglong; Van der Jeught, Kevin; Fang, Yuanzhang; Zhou, Zhuolong; Zhang, Lu; Frieden, Michael; Wang, Lifei; Luo, Zhenhua; Radovich, Milan; Schneider, Bryan P.; Deng, Yibin; Liu, Yunlong; Huang, Kun; He, Bin; Wang, Jin; He, Xiaoming; Zhang, Xinna; Ji, Guang; Lu, Xiongbin; Medical and Molecular Genetics, School of Medicine
Heterozygous deletion of chromosome 17p (17p) is one of the most frequent genomic events in human cancers. Beyond the tumor suppressor TP53, the POLR2A gene encoding the catalytic subunit of RNA polymerase II (RNAP2) is also included in a ~20-megabase deletion region of 17p in 63% of metastatic castration-resistant prostate cancer (CRPC). Using a focused CRISPR-Cas9 screen, we discovered that heterozygous loss of 17p confers a selective dependence of CRPC cells on the ubiquitin E3 ligase Ring-Box 1 (RBX1). RBX1 activates POLR2A by the K63-linked ubiquitination and thus elevates the RNAP2-mediated mRNA synthesis. Combined inhibition of RNAP2 and RBX1 profoundly suppress the growth of CRPC in a synergistic manner, which potentiates the therapeutic effectivity of the RNAP2 inhibitor, α-amanitin-based antibody drug conjugate (ADC). Given the limited therapeutic options for CRPC, our findings identify RBX1 as a potentially therapeutic target for treating human CRPC harboring heterozygous deletion of 17p.
In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy
(Springer Nature, 2023-01-24) Ou, Wenquan; Stewart, Samantha; White, Alisa; Kwizera, Elyahb A.; Xu, Jiangsheng; Fang, Yuanzhang; Shamul, James G.; Xie, Changqing; Nurudeen, Suliat; Tirada, Nikki P.; Lu, Xiongbin; Tkaczuk, Katherine H. R.; He, Xiaoming; Medical and Molecular Genetics, School of Medicine
Cancer immunotherapy that deploys the host’s immune system to recognize and attack tumors, is a promising strategy for cancer treatment. However, its efficacy is greatly restricted by the immunosuppressive (i.e., immunologically cold) tumor microenvironment (TME). Here, we report an in-situ cryo-immune engineering (ICIE) strategy for turning the TME from immunologically “cold” into “hot”. In particular, after the ICIE treatment, the ratio of the CD8+ cytotoxic T cells to the immunosuppressive regulatory T cells is increased by more than 100 times in not only the primary tumors with cryosurgery but also distant tumors without freezing. This is achieved by combining cryosurgery that causes “frostbite” of tumor with cold-responsive nanoparticles that not only target tumor but also rapidly release both anticancer drug and PD-L1 silencing siRNA specifically into the cytosol upon cryosurgery. This ICIE treatment leads to potent immunogenic cell death, which promotes maturation of dendritic cells and activation of CD8+ cytotoxic T cells as well as memory T cells to kill not only primary but also distant/metastatic breast tumors in female mice (i.e., the abscopal effect). Collectively, ICIE may enable an efficient and durable way to leverage the immune system for combating cancer and its metastasis.
Metformin Bicarbonate-Mediated Efficient RNAi for Precise Targeting of TP53 Deficiency in Colon and Rectal Cancers
(Elsevier, 2022) Xu, Jiangsheng; Liu, Yunhua; Liu, Sheng; Ou, Wenquan; White, Alisa; Stewart, Samantha; Tkaczuk, Katherine H.R.; Ellis, Lee M.; Wan, Jun; Lu, Xiongbin; He, Xiaoming; Medical and Molecular Genetics, School of Medicine
Colon and rectal cancers are the leading causes of cancer-related deaths in the United States and effective targeted therapies are in need for treating them. Our genomic analyses show hemizygous deletion of TP53, an important tumor suppressor gene, is highly frequent in both cancers, and the 5-year survival of patients with the more prevalent colon cancer is significantly reduced in the patients with the cancer harboring such deletion, although such reduction is not observed for rectal cancer. Unfortunately, direct targeting TP53 has been unsuccessful for cancer therapy. Interestingly, POLR2A, a gene essential for cell survival and proliferation, is almost always deleted together with TP53 in colon and rectal cancers. Therefore, RNA interference (RNAi) with small interfering RNAs (siRNAs) to precisely target/inhibit POLR2A may be an effective strategy for selectively killing cancer cells with TP53 deficiency. However, the difficulty of delivering siRNAs specifically into the cytosol where they perform their function, is a major barrier for siRNA-based therapies. Here, metformin bicarbonate (MetC) is synthesized to develop pH-responsive MetC-nanoparticles with a unique “bomb” for effective cytosolic delivery of POLR2A siRNA, which greatly facilitates its endo/lysosomal escape into the cytosol and augments its therapeutic efficacy of cancer harboring TP53 deficiency. Moreover, the MetC-based nanoparticles without functional siRNA show notable therapeutic effect with no evident toxicity or immunogenicity.

Browsing by Author "He, Xiaoming"

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