A5038157739- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- HIV Research and Treatment
- Adenosine and Purinergic Signaling
- RNA regulation and disease
- Cancer Mechanisms and Therapy
- Fungal and yeast genetics research
- Traumatic Brain Injury and Neurovascular Disturbances
- Protein Structure and Dynamics
- Ion Transport and Channel Regulation
- Chromosomal and Genetic Variations
- Cardiac Ischemia and Reperfusion
- Anesthesia and Neurotoxicity Research
- Photoreceptor and optogenetics research
- Circadian rhythm and melatonin
- ATP Synthase and ATPases Research
- Cytomegalovirus and herpesvirus research
- Nuclear Structure and Function
Cleveland Clinic Lerner College of Medicine
2015-2024
Icahn School of Medicine at Mount Sinai
2019-2023
Allen Institute for Brain Science
2019-2023
Cleveland Clinic
2018
McGill University
2006-2015
Nicholas Conor Institute
2009
Université de Montréal
2008
Shriners Hospitals for Children - Canada
2004
Western University
2004
Hereditary inclusion body myopathy associated with early-onset Paget disease of bone and frontotemporal dementia (hIBMPFTD) is a degenerative disorder caused by single substitutions in highly conserved residues p97/VCP. All mutations identified thus far cluster within the NH(2) domain or D1 ring, which are both required for communicating conformational changes to adaptor protein complexes. In this study, biochemical approaches were used identify consequences R155P A232E on p97/VCP structure....
The regeneration of peripheral nerves is guided by tracks formed through an interplay many cell types, but the underlying signaling pathways remain unclear. Here, we demonstrate that macrophages are mobilized ahead Schwann cells in nerve bridge after transection injury to participate building tracks. This requires function guidance receptor Plexin-B2, which robustly up-regulated infiltrating injured nerves. Conditional deletion Plexin-B2 myeloid lineage resulted not only macrophage...
Abstract Background HIV-1 Vpu targets newly synthesized CD4 receptor for rapid degradation by a process reminiscent of endoplasmic reticulum (ER)-associated protein (ERAD). is thought to act as an adaptor protein, connecting the ubiquitin (Ub)-proteasome degradative system through interaction with β-TrCP, component SCF β-TrCP E3 Ub ligase complex. Results Here, we provide direct evidence indicating that promotes trans -ubiquitination recruitment in human cells. To examine whether conjugation...
Abstract Hypomyelinating leukodystrophy (HLD) is an autosomal recessive disorder characterized by defective central nervous system myelination. Exome sequencing of two siblings with severe cognitive and motor impairment progressive hypomyelination characteristic HLD revealed homozygosity for a missense single-nucleotide variant (SNV) in EPRS1 (c.4444 C > A; p.Pro1482Thr), encoding glutamyl-prolyl-tRNA synthetase, consistent HLD15. Patient lymphoblastoid cell lines express markedly reduced...
The valosin-containing protein (p97) is a ubiquitin-dependent ATPase that plays central roles in ubiquitin proteasome system (UPS)-mediated degradation pathways. p97 has been recently identified as putative substrate of active Caspase-6 (Casp6) primary human neurons. Since Casp6 activated mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients' brains, the targeting by may represent an important step leads to UPS AD. Here, we show vitro vivo. cleavage recombinant generated two...
When endoplasmic reticulum (ER) homeostasis is perturbed, an adaptive mechanism triggered and named the unfolded protein response (UPR).Thus far, three known UPR signaling branches (IRE-1, PERK, ATF-6) mediate reestablishment of ER functions but can also lead to apoptosis if stress not alleviated.However, understanding molecular mechanisms integrating other functions, such as membrane traffic or endomembrane signaling, remains incomplete.We consequently sought identify new regulators...
LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions lead to diseases, including cancers. As a result, cells are actively engaged in preventing retrotransposition. This work reveals that Condensin II complex restricts retrotransposition both non-transformed transformed cell lines through inhibition of transcription translation. subunits, CAP-D3 CAP-H2, interact with members Gamma-Interferon Activated Inhibitor Translation...
Axon regeneration of dorsal root ganglia (DRG) neurons after peripheral axotomy involves reconfiguration gene regulatory circuits to establish regenerative programs. However, the underlying mechanisms remain unclear. Here, through an unbiased survey, we show that binding motif Bmal1, a central transcription factor circadian clock, is enriched in differentially hydroxymethylated regions (DhMRs) mouse DRG lesion. By applying conditional deletion Bmal1 neurons, vitro and vivo neurite outgrowth...
Aminoacyl-tRNA synthetases are ubiquitous, evolutionarily conserved enzymes catalyzing the conjugation of amino acids onto cognate tRNAs. During eukaryotic evolution, tRNA have been targets persistent structural modifications. These modifications can be additive, as in evolutionary acquisition noncatalytic domains, or subtractive, generation truncated variants through regulated mechanisms such proteolytic processing, alternative splicing, coding region polyadenylation. A unique variant is...
Injured neurons sense environmental cues to balance neural protection and axon regeneration, but the mechanisms are unclear. Here, we unveil aryl hydrocarbon receptor (AhR), a ligand-activated bHLH-PAS transcription factor, as molecular sensor key regulator of acute stress response at expense regeneration. We demonstrate responsiveness DRG sensory AhR signaling, which functions inhibit Conditional Ahr deletion in accelerates regeneration after sciatic nerve injury. partially mimics...