A5039173197- DNA Repair Mechanisms
- Radiopharmaceutical Chemistry and Applications
- Prostate Cancer Treatment and Research
- Lymphoma Diagnosis and Treatment
- DNA and Nucleic Acid Chemistry
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Neuroendocrine Tumor Research Advances
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Enzyme Structure and Function
- Sphingolipid Metabolism and Signaling
- Cancer and Skin Lesions
- Chemical Reactions and Isotopes
- Antibiotic Resistance in Bacteria
- Prostate Cancer Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Neuroblastoma Research and Treatments
- CNS Lymphoma Diagnosis and Treatment
- Biochemical and Molecular Research
- Shoulder Injury and Treatment
- Metal-Catalyzed Oxygenation Mechanisms
- ATP Synthase and ATPases Research
Stanford University
2019-2024
Lucile Packard Children's Hospital
2022
Society of Nuclear Medicine and Molecular Imaging
2022
Stanford Medicine
2019-2020
Stony Brook University
2008-2019
Menlo School
2019
Stony Brook University Hospital
2008-2018
Johns Hopkins University
2008-2015
New York Structural Biology Center
2014
Boston University
2014
Significance Ceramide is a bioactive lipid involved in numerous cellular functions and disease states that are critically dependent on its site of generation. nSMase2 generates ceramide at the inner leaflet plasma membrane therapeutic target for cancer neurological disorders. Although much known about nSMase2, there limited insight into molecular mechanisms regulating activity. Here we present crystal structure identify lipid-binding N-terminal domain as an allosteric activation domain. Key...
<sup>18</sup>F-DCFPyL (2-(3-{1-carboxy-5-[(6-<sup>18</sup>F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of PET/CT in patients biochemical recurrence (BCR) prostate cancer (PC). <b>Methods:</b> prospectively enrolled 72 men (52–91 y old; mean ± SD, 71.5 7.2) BCR after...
The metabolism of host cholesterol by Mycobacterium tuberculosis (Mtb) is an important factor for both its virulence and pathogenesis, although how why required not fully understood. Mtb uses a unique set catabolic enzymes that are homologous to those classical β-oxidation fatty acids but specific steroid-derived substrates. Here, we identify assign the substrate specificities two these enzymes, ChsE4-ChsE5 (Rv3504-Rv3505) ChsE3 (Rv3573c), carry out side chain oxidation in Mtb. Steady-state...
The Mycobacterium tuberculosis (Mtb) igr operon plays an essential role in Mtb cholesterol metabolism, which is critical for pathogenesis during the latent stage of infection. Here we report first structure a heterotetrameric MaoC-like enoyl-CoA hydratase, ChsH1-ChsH2, encoded by two adjacent genes from operon. We demonstrate that ChsH1-ChsH2 catalyzes hydration steroid enoyl-CoA, 3-oxo-4,17-pregnadiene-20-carboxyl-CoA, modified β-oxidation pathway side chain degradation. ligand-bound and...
Abstract Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, addition to the mitochondrial RNA polymerase, POLRMT. We have investigated organization initiation complex on light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) biochemical studies. Our EM results demonstrate a compact complex, suggesting that protein–protein interactions might help mediate initiation. that, absence DNA, only POLRMT form stable interaction,...
Abstract Reduced mitochondrial DNA copy number, mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these changes cause transcriptional reprogramming genes although the mechanism this cross talk remains unclear. Here, we provide evidence signaling regulates chromatin acetylation...
Eukaryotic t ranscription f actor B (TFB) proteins are homologous to KsgA/Dim1 ribosomal RNA (rRNA) methyltransferases. The mammalian TFB1, m itochondrial (TFB1M) factor is an essential protein necessary for mitochondrial gene expression. TFB1M mediates rRNA modification in the small subunit and thus plays a role analogous proteins. This has been linked dysfunctions leading maternally inherited deafness, aminoglycoside sensitivity diabetes. Here, we present first structural characterization...
8-Oxo-7,8,-dihydro-2′-deoxyguanosine triphosphate (8-oxo-dGTP) is a major product of oxidative damage in the nucleotide pool. It capable mispairing with adenosine (dA), resulting futile, mutagenic cycles base excision repair. Therefore, it critical that DNA polymerases discriminate against 8-oxo-dGTP at insertion step. Because its roles repair and non-homologous end joining, polymerase lambda (Pol λ) may frequently encounter 8-oxo-dGTP. Here, we have studied mechanisms 8-oxo-dGMP...
There has been tremendous growth in the development of theragnostics for personalized cancer diagnosis and treatment over past two decades. In prostate cancer, new generation specific membrane antigen (PSMA) small molecular inhibitor-based imaging agents achieve extraordinary tumor to background ratios allow their therapeutic counterparts deliver effective doses while minimizing normal tissue toxicity. The PSMA targeted molecule positron emission tomography (PET) 18F-DCFPyL...
Decoding of aberrant mRNAs leads to unproductive ribosome stalling and sequestration components the translation machinery. Bacteria have evolved three seemingly independent pathways resolve stalled complexes. The trans-translation process, orchestrated by hybrid transfer-messenger RNA (tmRNA) its essential protein co-factor, small B (SmpB), is principal quality control system for rescuing unproductively ribosomes. Two specialized alternative rescue pathways, coordinated ArfA ArfB, been...
Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner's syndrome and Dyskeratosis Congenita, while, progressive activates a DNA damage response leading to instability, typically observed in cancer cells senescent cells. Therefore, identifying mechanisms of length maintenance is critical for understanding human pathologies. In this paper we demonstrate that mitochondrial dysfunction plays causal role...
Bacterial conjugation, transfer of a single conjugative plasmid strand between bacteria, diversifies prokaryotic genomes and disseminates antibiotic resistance genes. As prerequisite for transfer, plasmid-encoded relaxases bind to cleave the transferred with sequence specificity. The crystal structure F TraI relaxase domain bound single-stranded DNA suggests binding specificity is partly determined by an intrastrand three-way base-pairing interaction. We showed previously that substitutions...
Non-conserved amino acids that are far removed from the active site can sometimes have an unexpected effect on enzyme catalysis. We investigated effects of alanine replacement residues distant replicative RB69 DNA polymerase, and identified a substitution in weakly conserved palm residue (D714A), renders incapable sustaining phage replication vivo. D714, located several angstroms away site, does not contact or incoming dNTP, our apoenzyme ternary crystal structures PolD714A mutant...
DOTATATE PET/CT is frequently used to evaluate indeterminant pulmonary nodules suspected be carcinoid. We report an unexpected case of hamartoma demonstrating 64Cu-DOTATATE uptake in a 43-year-old woman with slowly enlarging nodule. Histopathological staining showed somatostatin receptor 2 expression on vascular endothelial cells and proportion cartilage smooth muscle within the hamartoma.