A5016282476- Nuclear Structure and Function
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- COVID-19 Clinical Research Studies
- Mitochondrial Function and Pathology
- Cutaneous lymphoproliferative disorders research
- Lymphoma Diagnosis and Treatment
- T-cell and Retrovirus Studies
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- Telomeres, Telomerase, and Senescence
- Long-Term Effects of COVID-19
- PI3K/AKT/mTOR signaling in cancer
- Neonatal Health and Biochemistry
- Transplantation: Methods and Outcomes
- Cardiac Fibrosis and Remodeling
- Blood Coagulation and Thrombosis Mechanisms
- Lipid Membrane Structure and Behavior
- Health, Environment, Cognitive Aging
- Signaling Pathways in Disease
Duke University
2021-2022
Rockefeller University
2001-2020
Howard Hughes Medical Institute
1995-2019
New York University
1990-1995
Columbia University Irving Medical Center
1991-1995
NYU Langone Health
1993-1994
Cornell University
1986
NewYork–Presbyterian Hospital
1986
Ran is a nuclear Ras-like GTPase that required for the bidirectional transport of proteins and ribnucleoproteins across pore complex (NPC). A key regulator GTP/GDP cycle 70-kD Ran-GTPase-activating protein RanGAP1. Here, we report identification localization novel form Using peptide sequence analysis specific mAbs, RanGAP1 was found to be modified by conjugation ubiquitin-like protein. Immunoblot immunolocalization light EM demonstrated unmodified from exclusively cytoplasmic, whereas 90-kD...
The Ras-related nuclear protein, Ran, has been implicated in transport. By screening a HeLa cell λ expression library with Ran-GTP and sequencing overlapping cDNA clones, we have obtained the derived primary structure of protein calculated molecular mass 358 kDa. Using antibodies raised against an expressed segment this punctate surface staining by immunofluorescence microscopy that is characteristic for nucleoporins. Electron immunogold-decorated rat liver envelopes sublocalized 358-kDa at...
A mixed-oligonucleotide probe was used to identify four ras-like coding sequences in a human teratocarcinoma cDNA library. Two of these resembled the rho genes, one closely related H-, K-, and N-ras, shared only sequence domains that define ras gene superfamily. Homologs genes were found genomic DNA from variety mammals chicken. The transcriptionally active range cell types.
A mixed-oligonucleotide probe was used to identify four ras-like coding sequences in a human teratocarcinoma cDNA library. Two of these resembled the rho genes, one closely related H-, K-, and N-ras, shared only sequence domains that define ras gene superfamily. Homologs genes were found genomic DNA from variety mammals chicken. The transcriptionally active range cell types.
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”...
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...
BACKGROUNDIndividuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and extent to these affected by severity.METHODSWe performed a prospective cohort study individuals with symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, plasma samples used for multiplex...
For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, Sézary syndrome, are caused by human lymphotropic virus (HTLV-I/II). Arguments against this concept included finding only a small number of MF patients have antibodies to HTLV-I/II attempts detect proviral sequences mere Southern hybridization extracted DNA usually met with failure. However, we reported repeatedly HTLV-like particles emerge in blood mononuclear...
In the USA, Kaposi's sarcoma associated with acquired immunodeficiency syndrome (AIDS-KS) is ten times more common in homosexual or bisexual men than heterosexual AIDS. One explanation for this finding that AIDS-KS may be caused by an infectious agent. Because there a high incidence of human papillomavirus (HPV) infection, especially HPV-16, men, we have sought HPV DNA sequences sarcoma. We used polymerase chain reaction primer pair specific highly conserved E6 region HPV-16 to detect...
In eukaryotic cells, the faithful segregation of daughter chromosomes during cell division depends on formation a microtubule (MT)-based bipolar spindle apparatus. The Nuclear Mitotic Apparatus protein (NuMA) is recruited from interphase nuclei to MTs mitosis. carboxy terminal domain NuMA binds MTs, allowing dimer function as "divalent" crosslinker that bundles MTs. messenger RNA export factor, Rae1, also Lowering Rae1 or increasing levels in cells results abnormalities. We have identified...
Endogenous DNA sequences related to retroviruses are probably present in all primates. By using approaches based on the polymerase chain reaction, two separate studies have revealed evolutionary history of some these sequences. In first study, a retrovirus-like reverse transcriptase (RT) sequence homologous that Baboon endogenous virus (BaEV) has been identified both Old World monkeys and African apes, but not humans or Asian apes. This RT is highly conserved at amino acid level, nucleotide...
Ran/TC4, a member of the RAS gene superfamily, encodes an abundant nuclear protein that binds and hydrolyzes GTP. Transient expression Ran/TC4 mutant deficient in GTP hydrolysis blocked DNA replication, suggesting role for regulation cell cycle progression. To test this possibility, we exploited efficient transfection system, involving introduction cDNAs pMT2 vector into 293/Tag cells, to analyze phenotypes associated with wild-type expression. Expression inhibited proliferation transfected...
Because of seronegativity and absence a leukemic phase in most patients with mycosis fungoides, role for the human T-lymphotropic virus type I (HTLV-I) this disease has remained tenuous. Virus particles are not seen fresh isolates skin or blood lymphocytes malignant cells (Sézary cells) have been difficult to culture. The availability growth factors biomolecular techniques prompted renewed attempt find evidence infection these patients. We report here successful culture 17 fungoides 1...
The cytokine IFN-α is secreted during viral infections and has been shown to inhibit telomerase activity accelerate T cell differentiation in vivo. However, the mechanism for this inhibition not clear. In study, we show that inhibits both transcription translation of human reverse transcriptase (hTERT), catalytic component telomerase, activated CD8(+) cells. This was associated with increased repressor hTERT E2 factor decreased activation NF-κB promotes transcription. However did affect...
The small Ras-related GTP binding and hydrolyzing protein Ran has been implicated in a variety of processes, including cell cycle progression, DNA synthesis, RNA processing, nuclear-cytosolic trafficking both proteins. Like other GTPases, appears to function as switch: Ran-GTP Ran-GDP levels are regulated by guanine nucleotide exchange factors GTPase activating proteins, interact differentially with one or more effectors. One such putative effector, Ran-binding 1 (RanBP1), interacts...
The interaction of fresh serum with promastigotes Leishmania major, L. donovani, mexicana mexicana, amazonensis, and braziliensis guyanensis results in lysis all strains tested either human or guinea pig at 37 C for 30 min. Lysis does not occur the cold requires divalent cations complement that is active hemolytically. Serum deficient eighth component lytic. proceeds fully containing EGTAMg2+ fourth component. These species consume only small amounts C4 from do require calcium to optimally...
Two cryo-EM structures of IGF2R at different pH values imply the mechanism for its ligand release in endocytic compartments.
ABSTRACT Introduction Subjects recovering from COVID-19 frequently experience persistent respiratory ailments; however, little is known about the underlying biological factors that may direct lung recovery and extent to which these are affected by severity. Methods We performed a prospective cohort study of subjects with symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, plasma samples used for multiplex profiling inflammatory, metabolic, angiogenic, fibrotic...
Centromere protein F (CENP-F) is a component of the kinetochore and regulator cell cycle progression. CENP-F recruits dynein transport machinery orchestrates several cycle-specific events, including nucleus, mitochondria chromosomes. A key regulatory step for these functions likely G2 phase-specific export from nucleus to cytosol, where cytoplasmic resides; however, molecular mechanism this process elusive. Here, we have identified 3 phosphorylation sites within bipartite classical nuclear...
Kap121 interacts with an intrinsically disordered region of Nup53 to allosterically modulate binding partner nucleoporins.