A5013451104- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Anesthesia and Neurotoxicity Research
- Bacterial Genetics and Biotechnology
- Anesthesia and Sedative Agents
- ATP Synthase and ATPases Research
- Coenzyme Q10 studies and effects
- Cardiac Ischemia and Reperfusion
- Cardiac, Anesthesia and Surgical Outcomes
- Probiotics and Fermented Foods
- Legume Nitrogen Fixing Symbiosis
- Infectious Diseases and Mycology
- Cardiomyopathy and Myosin Studies
- Microbial Inactivation Methods
- Autism Spectrum Disorder Research
- Intensive Care Unit Cognitive Disorders
- Lipid Membrane Structure and Behavior
- Ubiquitin and proteasome pathways
- Adenosine and Purinergic Signaling
- Bacillus and Francisella bacterial research
- Cardiovascular Issues in Pregnancy
- Antifungal resistance and susceptibility
- Sinusitis and nasal conditions
- Bacteriophages and microbial interactions
- Diffusion and Search Dynamics
Columbia University Irving Medical Center
2017-2025
National Institute of General Medical Sciences
2021
Hôpital de la Timone
2017
UConn Health
2009-2013
Wesleyan University
2006
Dormant bacterial spores are extraordinarily resistant to environmental insults and vectors of various illnesses. However, cannot cause disease unless they germinate become vegetative cells. The molecular details initiation germination not understood, but proteins essential in early stages germination, such as nutrient germinant receptors (GRs) GerD, located the spore inner membrane. In this study, we examine how these organized dormant Bacillus subtilis by expressing fluorescent protein...
To determine effects of inner membrane lipid composition on Bacillus subtilis sporulation and spore properties.The absence genes encoding biosynthetic enzymes had no effect B. sporulation, although the expected lipids were absent from spores' membrane. The rate germination with nutrients was decreased c. 50% mutants that lacked major cardiolipin (CL) synthase another enzyme for synthesis a phospholipid. Spores lacking minor CL or an essential glycolipid exhibited 50-150% increases in rates...
Fragile X syndrome (FXS) is the leading known inherited intellectual disability and most common genetic cause of autism. The full mutation results in transcriptional silencing Fmr1 gene loss fragile mental retardation protein (FMRP) expression. Defects neuroenergetic capacity are to a variety neurodevelopmental disorders. Thus, we explored integrity forebrain mitochondria knockout mice during peak synaptogenesis. We found inefficient thermogenic respiration due futile proton leak KO caused...
As previously reported, gerP Bacillus subtilis spores were defective in nutrient germination triggered via various germinant receptors (GRs), and the defect was eliminated by severe spore coat defects. The spores' GR-dependent had a longer lag time between addition of germinants initiation rapid release dipicolinic acid (DPA), but times for >90% DPA from individual identical wild-type spores. also GR-independent with its associated Ca(2+) divalent cation (CaDPA) germinated better than...
Abstract Pathological opening of the mitochondrial permeability transition pore (mPTP) is implicated in pathogenesis many disease processes such as myocardial ischemia, traumatic brain injury, Alzheimer's disease, and diabetes. While we have gained insight into mPTP biology over last several decades, lack translation this knowledge successful clinical therapies underscores need for continued investigation use different approaches to identify novel regulators with hope elucidating new...
Background: A functional anesthetic target has long been suspected to reside within mitochondria and disruption of bioenergetic capacity is believed play a role in the response. Unfortunately, exact mechanism by which changes mitochondrial activity result clinically relevant endpoints remains unknown. Here we leveraged knowledge propofol toxicity guide drug discovery uncover previously unknown pharmacological mitochondria. We hypothesized that, like propofol, quinone analogs would interfere...
Germination of Bacillus subtilis spores can be triggered by the binding specific nutrients, called germinants, to germinant receptors (GRs) in spore's inner membrane. This interaction eventually initiates, with variable time delays, release dipicolinic acid and cations from spore core--a key step germination. The kinetics this process are highly heterogeneous for individual spores. In work, we sought investigate how germination heterogeneity was controlled. particular, tested whether rates...
Abstract Background Propofol infusion syndrome (PRIS) is a potentially lethal consequence of long-term propofol administration. Children are vulnerable and cardiac involvement often prominent associated with mortality. We aimed to determine the mechanism toxicity in newborn mice, hypothesizing that would induce discrete defects within immature mitochondria. Methods Newborn murine mitochondria were exposed or intralipid vitro. Non-exposed served as controls. Mitochondrial respiration membrane...
Infants and children are vulnerable to developing propofol infusion syndrome (PRIS) young age is a risk factor. Cardiac involvement often prominent associated with death. However, the mechanisms of pediatric PRIS poorly understood because paucity investigation lack gold standard animal model. Unfortunately, in vivo modeling newborn mouse not feasible would be complicated by confounders. Thus, we focused on propofol-induced cardiotoxicity aimed develop an ex-vivo model isolated-perfused...
The potential for long-term neurotoxic effects of anesthetics on the developing human brain has led to intensified research in this area. To date, evidence been inconclusive, but a large body animal continues demonstrate cause concern. On April 14 and 15, 2018 sixth biennial Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) study symposium was held at Morgan Stanley Children’s Hospital New York. This brought together clinicians researchers served as platform review preclinical...
The mitochondrial permeability transition pore (mPTP) is a voltage-gated, nonselective, inner membrane (IMM) mega-channel important in health and disease. mPTP mediates leakage of protons across the IMM during low-conductance opening specifically inhibited by cyclosporine A (CsA). Coenzyme Q (CoQ) regulator mPTP, tissue-specific differences have been found CoQ content open probability forebrain heart mitochondria newborn mouse model fragile X syndrome (FXS, Fmr1 knockout). We developed...
Eisler, Lisa MD, MS; Knapp, Andrew MD; Griffiths, Keren K. PhD; Houck, Constance S. Nafiu, Olubukola O. MD Author Information
Abstract Divalent metal ions are essential for maintaining functional states of the DNA molecule. Their participation in structure is modulated by base sequence and varies depending on nature ion. The present investigation addresses interaction Ca2+ with a tandem repeat two CA dinucleotides, (CA)2/(TG)2. binding to monitored nuclear magnetic resonance (NMR) spectroscopy using chemical shift mapping. Parallel experiments monitor Mg2+ as well each ion duplex which (CA)2/(TG)2 eliminated....
The mitochondrial permeability transition pore (mPTP) is a voltage-gated, nonselective, inner membrane (IMM) mega-channel important in health and disease. mPTP mediates leakage of protons across the IMM during low-conductance opening specifically inhibited by cyclosporine A (CsA). Coenzyme Q (CoQ) regulator mPTP, tissue-specific differences have been found CoQ content open probability forebrain heart mitochondria newborn mouse model fragile X syndrome (FXS, Fmr1 knockout). We developed...
Fragile X syndrome (FXS) is the leading known inherited intellectual disability and most common genetic cause of autism. The full mutation results in transcriptional silencing Fmr1 gene loss fragile mental retardation protein (FMRP) expression. Defects neuroenergetic capacity are to a variety neurodevelopmental disorders. Thus, we explored integrity forebrain mitochondria knockout mice during peak synaptogenesis. We found inefficient thermogenic respiration due futile proton leak KO caused...
Translational science seeks to accelerate the multi-step process by which scientific discoveries are transformed into therapies that can improve health of individuals and their communities. To facilitate crossing traditional boundaries between basic clinical research for instance, a systematic understanding operational principles underlie each step translational cycle is developed identify address barriers translation. Skills required scientists, such as being systems thinkers innovators,...