A5014099489- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Parkinson's Disease Mechanisms and Treatments
- biodegradable polymer synthesis and properties
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Ion channel regulation and function
- RNA Research and Splicing
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Neurological diseases and metabolism
Columbia University Irving Medical Center
2019-2025
Columbia University
2018
Washington State University
2009
Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here this impairment crosstalk between mitochondria and ER impedes use glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids sustain energy production. Over time, deficiency alters electron flow active/dormant status complex I spinal cord tissues,...
In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial (CrMN) are spared until late stages the disease. Using rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) SpMNs CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 insoluble p62 than over time. have higher proteasome activity degrade misfolded proteins intrinsically more resistant chemically-induced proteostatic stress SpMNs....
The highly charged histone N-terminal domains are engaged in inter- and intra-nucleosomal interactions, contain a host of sites used for posttranslational modification. We have studied the effect deleting residues 30–37 from domain H2B yeast cells, on nucleotide excision repair (NER) following UV irradiation, as these cells quite sensitive to UV. find that Δ30–37 exhibit reduced NER efficiency at three specific chromatin loci: transcriptionally active, RPB2 locus; silenced, nucleosome-loaded...
Abstract Mitochondrial defects are a common hallmark of familial and sporadic forms amyotrophic lateral sclerosis (ALS). However, the origin these defects, including reduced pyruvate metabolism oxygen consumption, is poorly understood. These metabolic functions regulated in specialized endoplasmic reticulum (ER) domains close contact with mitochondria, called mitochondrial-associated ER membranes (MAM). Recently it has been shown that MAM disrupted ALS, but connection between dysregulation...
In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial (CrMN) are spared until late stages the disease. Using rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) SpMNs CrMNs, we now report that ESC-derived CrMNs accumulate less human superoxide dismutase 1 (hSOD1) insoluble p62 than over time. rely more on ubiquitin proteasome system degrade misfolded proteins intrinsically resistant chemically-induced...
Abstract Mitochondria-associated ER membranes (MAM) are transient functional domains in the endoplasmic reticulum (ER) close apposition to mitochondria involved multiple metabolic functions, including regulation of functionality. Specifically, MAM interactions with contribute mitochondrial dynamics, calcium transference between both organelles and composition membranes. In addition, recent data indicate that alterations MAM-mitochondria contacts associated impairments glucose metabolism...
Summary In amyotrophic lateral sclerosis (ALS) spinal motor neurons (SpMN) progressively degenerate while a subset of cranial (CrMN) are spared until late stages the disease. Using rapid and efficient protocol to differentiate mouse embryonic stem cells (ESC) SpMNs CrMNs, we now report that ESC-derived CrMNs accumulate less human (h)SOD1 insoluble p62 than over time. have higher proteasome activity degrade misfolded proteins intrinsically more resistant chemically-induced proteostatic stress...