A5089522697- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Cholesterol and Lipid Metabolism
- Hedgehog Signaling Pathway Studies
- Ion Channels and Receptors
- Genomics and Chromatin Dynamics
- Aluminum Alloys Composites Properties
- Immunotherapy and Immune Responses
- Endoplasmic Reticulum Stress and Disease
- Lipoproteins and Cardiovascular Health
- Immune Response and Inflammation
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Lysosomal Storage Disorders Research
- RNA Interference and Gene Delivery
- Acute Lymphoblastic Leukemia research
- Adolescent Sexual and Reproductive Health
- Acute Myeloid Leukemia Research
- Cell Adhesion Molecules Research
- RNA modifications and cancer
- Parasites and Host Interactions
- Diabetes Management and Research
The University of Texas Southwestern Medical Center
2017-2025
Indiana University – Purdue University Indianapolis
2010-2025
Suzhou Traditional Chinese Medicine Hospital
2017-2024
New York University
2011-2024
Indiana University School of Medicine
2013-2024
Nanjing University of Chinese Medicine
2022-2024
Taiyuan University of Technology
2024
Guangzhou Blood Center
2024
University of California, Los Angeles
2018-2023
Ministry of Agriculture and Rural Affairs
2023
Abstract Purpose: This study examined the feasibility, efficacy (abscopal effect), and immune effects of TGFβ blockade during radiotherapy in metastatic breast cancer patients. Experimental Design: Prospective randomized trial comparing two doses blocking antibody fresolimumab. Metastatic patients with at least three distinct sites whose tumor had progressed after one line therapy were to receive 1 or 10 mg/kg fresolimumab, every 3 weeks for five cycles, focal a site week (three 7.5 Gy),...
Significance Niemann–Pick C1 (NPC1) and C2 (NPC2) cooperate in the export of LDL-derived cholesterol from lysosomes; mutations these proteins lead to type C disease. We present here crystal structure an NPC1–NPC2 complex show that amino acid residues are important for this interaction vitro also lysosomes cultured cells. These data provide key information related mechanism by which catalyze transport form basis a molecular model how is transferred NPC2 onto NPC1 protein.
Abstract Pharmacological inhibition of vacuolar-type H + -ATPase (V-ATPase) by its specific inhibitor can abrogate tumor metastasis, prevent autophagy, and reduce cellular signaling responses. Bafilomycin A1, a member macrolide antibiotics an autophagy inhibitor, serves as potent V-ATPases inhibitor. Although there are many V-ATPase structures reported, the molecular basis inhibitors on remains unknown. Here, we report cryo-EM structure bafilomycin A1 bound intact bovine at overall...
Virulent enteric pathogens such as Escherichia coli strain O157:H7 rely on acid-resistance (AR) systems to survive the acidic environment in stomach. A major component of AR is an arginine-dependent arginine:agmatine antiporter that expels intracellular protons. Here, we report crystal structure AdiC, from E. and a member amino acid/polyamine/organocation (APC) superfamily transporters at 3.6 resolution. The overall fold similar several Na+-coupled symporters. AdiC contains 12 transmembrane...
Flat and depressed colon neoplasms are an increasingly recognized precursor for colorectal cancer (CRC) in Western populations. High-definition chromoscopy is used to increase the yield of colonoscopy flat neoplasms; however, its role average-risk patients undergoing routine screening remains uncertain.Average-risk referred at four U.S. medical centers were randomized high-definition chromocolonoscopy or white light colonoscopy. The primary outcomes, with least one adenoma number adenomas...
Significance Niemann–Pick C1 protein (NPC1) is a late-endosomal membrane required for transport of LDL-derived cholesterol into cells and Ebola virus entry; mutations cause type C disease. NPC1 contains “sterol-sensing domain” (SSD) that also appears in several key regulatory proteins biosynthesis, uptake, signaling. We present here the crystal structure large portion human NPC1, which reveals architecture SSD, including cavity accessible both vertically to endosome lumen laterally “luminal”...
Birinapant (1) is a second-generation bivalent antagonist of IAP proteins that currently undergoing clinical development for the treatment cancer. Using range assays evaluated cIAP1 stability and oligomeric state, we demonstrated 1 stabilized cIAP1-BUCR (BIR3-UBA-CARD-RING) dimer promoted autoubiquitylation in vitro. Smac-mimetic 1-induced loss cIAPs correlated with inhibition TNF-mediated NF-κB activation, caspase tumor cell killing. Many first-generation Smac-mimetics such as compound A...
First reported in 1999, germline runt-related transcription factor 1 (RUNX1) mutations are a well-established cause of familial platelet disorder with predisposition to myeloid malignancy (FPD-MM). We present the clinical phenotypes and genetic detected 10 novel RUNX1-mutated FPD-MM families. Genomic analyses on these families 2 partial gene deletions, 3 mutations, 5 recurrent as RUNX1 alterations leading FPD-MM. Combining genomic data from herein aggregated published sets resulted 130...
It takes two to signal The Hedgehog (HH) signaling pathway is important in development, and excessive HH associated with cancer. Signaling occurs through the G protein–coupled receptor Smoothened. repressed by membrane Patched-1 (PTCH1), this inhibition relieved when PTCH1 binds secreted protein HH. Two recent papers have described structures of bound PTCH1, but surprisingly, each a different binding epitope on Qi et al. present cryo–electron microscopy structure that explains apparent...
This study was designed to investigate whether ginsenoside Rb1 (Rb1) and compound K (CK) ameliorated insulin resistance by suppressing endoplasmic reticulum (ER) stress-induced inflammation in adipose tissue.To induce ER stress, epididymal tissue from mice or differentiated 3T3 adipocytes were exposed high glucose. The effects of CK on reactive oxygen species production, TXNIP/NLRP3 inflammasome activation, inflammation, signaling glucose uptake detected western blot, emzyme-linked...
Article6 June 2018Open Access Source DataTransparent process miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking Katherine A Pillman orcid.org/0000-0002-5869-889X Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, SA, Search more papers this author Caroline Phillips Suraya Roslan John Toubia B Kate Dredge Andrew G Bert Rachael Lumb Daniel P Neumann Xiaochun Li Simon J Conn...
Significance The Niemann–Pick C1 (NPC1) protein is responsible for transporting LDL-derived cholesterol out of late endosomes. Mutations in NPC1 lead to the fatal Type C disease. We present here an improved structure at 3.3 Å and decipher details its C-terminal luminal domain (CTD), which could not be resolved previous structures. In particular, a loop stabilized by pair disulfide bonds CTD binds N-terminal through loop–loop interaction. show that this interaction important transport...
Significance Cholesterol is an essential component of animal cell membranes whose level in cells maintained within a narrow range. actively excreted from by two ATP-binding cassette (ABC) transporters, ABCG5–ABCG8 (G5G8) the liver and gut ABCG1 (G1) macrophages. The mechanism(s) which these proteins translocate rigid, planar sterol molecules across membrane bilayer remain unknown. Here, we report structure human G1 G5G8 their unbound cholesterol-bound states. We also determined bound to ATP....
Sphingosine-1-phosphate (S1P) regulates immune cell trafficking, angiogenesis, and vascular function via its five receptors. Inherited mutations in S1P receptor 2 (S1PR2) occur individuals with hearing loss, acquired S1PR2 G α13 a malignant lymphoma. Here, we present the cryo–electron microscopy structure of S1P-bound coupled to heterotrimeric 13 . Interaction between intracellular loop (ICL2) transmembrane helix 4 confines ICL2 engage α5 Transforming growth factor–α shedding assays...