A5048978036- PARP inhibition in cancer therapy
- EEG and Brain-Computer Interfaces
- Estrogen and related hormone effects
- Prostate Cancer Treatment and Research
- Neurobiology and Insect Physiology Research
- Neuroscience and Neural Engineering
- COVID-19 Clinical Research Studies
- Cephalopods and Marine Biology
- Hormonal and reproductive studies
- Muscle activation and electromyography studies
- Adrenal Hormones and Disorders
- Motor Control and Adaptation
- Allergic Rhinitis and Sensitization
- SARS-CoV-2 and COVID-19 Research
- Vitamin D Research Studies
- Diabetes and associated disorders
- Sexual Differentiation and Disorders
- Asthma and respiratory diseases
- Respiratory and Cough-Related Research
- Genetics, Bioinformatics, and Biomedical Research
- Photoreceptor and optogenetics research
- Robot Manipulation and Learning
- Sports Performance and Training
- Zebrafish Biomedical Research Applications
- Cardiovascular and exercise physiology
Cleveland Clinic Lerner College of Medicine
2019-2023
Cerner (United States)
2021
Cleveland Clinic
2020-2021
Case Western Reserve University
2010-2019
Analysis and control of neural circuitry requires the ability to selectively activate or inhibit neurons. Previous work showed that infrared laser light excited activity in endogenous unmyelinated myelinated axons. However, inhibition neuronal firing with was only observed limited cases, is not well understood precisely controlled. Using an experimentally tractable preparation for detailed investigation a validation, we report it possible transiently electrically-initiated axonal activation,...
Abstract The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 pulmonary tissues that may increase susceptibility or severity males. This hypothesis the subject several clinical trials anti-androgen therapies around world. Here, we investigated sex-associated human mouse lungs interrogated possibility pharmacologic...
After androgen deprivation, prostate cancer frequently becomes castration resistant (CRPC), with intratumoral production from extragonadal precursors that activate the receptor pathway. 3β-Hydroxysteroid dehydrogenase-1 (3βHSD1) is rate-limiting enzyme for synthesis, which together lead to CRPC. Here, we show cancer-associated fibroblasts (CAFs) increased epithelial 3βHSD1 expression, induced activated receptor, and Unbiased metabolomics revealed CAF-secreted glucosamine specifically 3βHSD1....
Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied human airways.Objectives: To measure whether and its ligands associated with asthma outcomes.Methods: We compared the effects of expression on lung function, symptom scores, fractional exhaled nitric oxide (FeNO) adults enrolled SARP (Severe Asthma Research Program). The impact sex androgens outcomes was also evaluated validation studies Cleveland Clinic Health System NHANES (U.S....
Abstract The sex discordance in COVID-19 outcomes has been widely recognized, with males generally faring worse than females and a potential link to steroids. A plausible mechanism is androgen-induced expression of TMPRSS2 and/or ACE2 pulmonary tissues that may increase susceptibility or severity males. This hypothesis the subject several clinical trials anti-androgen therapies around world. Here, we investigated sex-associated human mouse lungs interrogated possibility pharmacologic...
We describe the development of a course to teach modeling and mathematical analysis skills students biology with strong backgrounds in mathematics, physics, or engineering. The two groups have different ways learning material often negative feelings toward area knowledge that they find difficult. To give sense mastery each area, several complementary approaches are used course: 1) “live” textbook allows explore models processes interactively; 2) benchmark problems providing key on which make...
Many behaviors require reliably generating sequences of motor activity while adapting the to incoming sensory information. This process has often been conceptually explained as either fully dependent on input (a chain reflex) or independent (an idealized central pattern generator, CPG), although consensus field is that most neural generators lie somewhere between these two extremes. mathematical models use limit cycles generate sequence behaviors, but other models, such a heteroclinic...
Multifunctionality, the ability of one peripheral structure to generate multiple, distinct behaviors1, allows animals rapidly adapt their behaviors changing environments. The marine mollusk Aplysia californica provides a tractable system for study multifunctionality. During feeding, generates several types using same feeding apparatus, buccal mass. ganglia that control these contain number large, identified neurons are accessible electrophysiological study. activity has been described in...
Steroid hormones and their respective nuclear receptors are essential mediators in numerous physiologic pathophysiologic processes, ranging from regulation of metabolism, immune function, reproductive processes to the development hormone-dependent cancers such as those breast prostate. Because steroids must enter cells before activating receptors, understanding mechanisms by which cellular uptake occurs is critical, yet a clear these has been elusive. It generally assumed that...
Some behaviors occur in obligatory sequence, such as reaching before grasping an object. Can the earlier behavior serve to prepare musculature for later behavior? If it does, what is underlying neural mechanism of preparation? To address this question, we examined two feeding marine mollusk Aplysia californica , one which must precede second: biting and swallowing. Biting attempt grasp food. When that successful, animal immediately switches swallowing ingest The main muscle responsible...
In animals with large identified neurons (e.g. mollusks), analysis of motor pools is done using intracellular techniques1,2,3,4. Recently, we developed a technique to extracellularly stimulate and record individual in Aplysia californica5. We now describe protocol for this uniquely identify characterize within pool. This extracellular has advantages. First, electrodes can through the sheath5, so it does not need be removed. Thus, will healthier experiments than ones. Second, if ganglia are...
To survive, animals must use the same peripheral structures to perform a variety of tasks. How does nervous system employ one muscle multiple functions? We addressed this question through work on I3 jaw marine mollusk Aplysia californica's feeding system. This mediates retraction Aplysia's food grasper in responses and is innervated by pool identified neurons that activate different regions. One motor neuron, B38, active protraction phase, rather than suggesting has an additional function....
BACKGROUND. Genetics of estrogen synthesis and breast cancer risk has been elusive. The 1245A→C missense-encoding polymorphism in HSD3B1, which is common White populations, functionally adrenal permissive increases the aromatase substrate androstenedione. We hypothesized that homozygous inheritance adrenal-permissive HSD3B1(1245C) associated with postmenopausal receptor–positive (ER-positive) cancer.
A growing body of evidence suggests a role for androgens in asthma and control. This includes sex discordance disease rates that changes with puberty, experiments mice showing reduce airway inflammation, reported association between androgen receptor (AR) expression severity patients. We set out to determine whether AR differs patients healthy controls. analyzed data from 8 publicly available sets gene profiling epithelial cells obtained both control individuals. found was lower than...
Sensory feedback shapes ongoing behavior and may produce learning memory. Motor responses to edible or inedible food in a reduced Aplysia preparation were examined test how sensory affects Feeding patterns initiated by applying cholinomimetic onto the cerebral ganglion. Feedback from buccal muscles increased response variability rate. Repeated application of caused decreased responses, expressed part lengthening protractions. Swallowing strips “edible” food, which intact animals induces that...
Abstract Background The germline variant rs1047303 (HSD3B1[1245A/C]), restricting or enabling production of potent androgens and estrogens from adrenal precursors, affects outcomes castration-resistant prostate cancer is associated with estrogen receptor positivity in postmenopausal breast cancer. Like cancer, endometrial another malignancy hormone-dependent hormone-independent subtypes. We hypothesized that adrenal-restrictive HSD3B1 genotype would associate Methods employed a previously...
Dynamics of Biological Systems, the IBI Prize–winning module, brings mathematics into biology laboratory.
To understand how behaviors arise in animals, it is necessary to investigate both the neural circuits and biomechanics of periphery. A tractable model system for studying multifunctional control feeding apparatus marine mollusk Aplysia californica. Previous silico roboto models have investigated nervous muscular systems interact this system. However, these are still limited their ability match vivo data qualitatively quantitatively. We introduce a new neuromechanical that combines modified...
Abstract Background Conversion of adrenally produced dehydroepiandrosterone (DHEA) to the potent androgen dihydrotestosterone (DHT) is an important mechanism by which prostate cancer reaches castration resistance. At start this pathway a branch point at DHEA can be converted Δ 4 ‐androstenedione enzyme 3β‐hydroxysteroid dehydrogenase (3βHSD) or 5 ‐androstenediol 17βHSD. To better understand process, we studied kinetics these reactions in cells. Methods Prostate cells (LNCaP cell line) were...
Abstract Context A sex discordance in COVID exists, with males disproportionately affected. Although steroids may play a role this discordance, no definitive genetic data exist to support androgen-mediated immune suppression neither for viral susceptibility nor adrenally produced androgens. Objective The common adrenal-permissive missense-encoding variant HSD3B1(1245C) that enables androgen synthesis from adrenal precursors and has been linked of inflammation severe asthma was investigated...