A highlight of the Kopin Memorial Symposium will be the poster session. Presenters will provide insight on their work, why they're important and how their work relates to Dr. Irv Kopin.
Poster Presenters
- Nicole Bechmann
- Oladi Bentho
- Caroline Cuoco
- Chelsea Fearce
- John P. Finberg
- Richard Imrich
- Risa Isonaka
- Yunden Jinsmaa
- Miji Kim
- Kathryn Luderman
- Amy Moritz
- Chiso Nwokafor
- Alberto Palma
- Kayla Schardien
- Diana Willmes
- Adrianna Wilson
- Rebecca Windmueller
- Moussa Youdim
Poster Moderators
- Murray Esler, M.D., Professor Baker Heart and Diabetes Institute Australia
- Yehonatan Sharabi, M.D., Associate Professor, Tel Aviv Univ. Sackler Faculty of Medicine, Israel
Abstracts
Nicole Bechmann
Go Top|
Influence of extrinsic and intrinsic hypoxia on catecholamine biosynthesis in absence or present of hypoxia inducible factor 2 (HIF2) in pheochromocytoma cells |
|
|---|---|
|
Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing neuroendocrine tumors with diverse aggressiveness. PPGLs with an activation in pseudohypoxic pathways are associated with an immature catecholamine phenotype and carry a higher risk for metastatic spread... |
View full abstract |
Oladi Bentho
Go Top|
Admission plasma levels of catechols predict outcome in patients with intracerebral hemorrhage |
|
|---|---|
| Intracerebral hemorrhage (ICH) affects 5 million people worldwide, without good strategies for treatment or prevention. ICH has a 30-day mortality of approximately 40%, and only 10-25% of patients return to functional independence. Immediately following the acute hemorrhage there is activation of the hypothalamic-pituitary adrenal (HPA) axis and the sympathetic nervous system (SNS). Whether admission plasma levels of catechols predict outcome has been unknown... |
View full abstract |
Caroline Cuoco
Go Top|
Characterization of the Novel Anti-Cancer Therapeutic ONC201 and Related Analogs as an Non-Competitive Antagonists of the D2 Dopamine Receptor |
|
|---|---|
| ONC201 is the first member of a new class of anti-cancer small molecules called imipridones to be investigated in clinical trials for select advanced cancers. The anti-cancer properties of the parent compound were first discovered in a phenotypic screen as a p53 independent inducer of the immune cytokine TRAIL and tumor cell death. Tumor cell signaling studies revealed that ONC201 causes a dual inactivation of Akt/ERK that drives Foxo3a-mediated TRAIL gene induction. Recent studies identified that ONC201 also selectively antagonizes D2- like dopamine receptors (D2R, D3R, D4R) at therapeutically relevant concentrations... |
View full abstract |
Chelsea Fearce
Go Top|
Discovery and characterization of a novel series of D2 dopamine receptor-selective antagonists through iterative chemistry of a bromodomain and extra-terminal protein inhibitor |
|
|---|---|
|
Recent findings by several groups have highlighted the potential for targeting D2 dopamine receptors (D2R) in cancer pharmacotherapy. In addition to being an important therapeutic target for psychiatric disorders (all current FDA-approved antipsychotics are D2R antagonists), it has been proposed that D2Rs are over-expressed in several types of cancer and that D2R inhibition is associated with anti-proliferative effects... |
View full abstract |
John Finberg
Go Top|
Neuroprotective effect of static magnetic field2 dopamine receptor-selective antagonists through iterative chemistry of a bromodomain and extra-terminal protein inhibitor |
|
|---|---|
|
Background: Magnetic fields are known to affect biological systems. We have observed an anti-apoptotic effect of moderate-strength (50G) static magnetic field (SMF) in rat primary neuronal cultures... |
View full abstract |
Richard Imrich
Go Top|
Brain-derived neurotrophic factor response to mental stress in patients with newly diagnosed multiple sclerosis |
|
|---|---|
|
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system leading to demyelination. Brain-derived neurotrophic factor (BDNF) appears to play a role in processes of remyelination mediated mainly by surviving oligodendrocytes during disease remission. Normal or decreased BDNF concentrations were found in plasma of patients with MS... |
View full abstract
|
Risa Isonaka
Go Top|
Diagnosing synucleinopathy during life: Alpha-synuclein deposition within sympathetic neurons in Lewy body diseases with neurogenic orthostatic hypotension |
|
|---|---|
|
Background: Lewy body diseases such as Parkinson disease with orthostatic hypotension, pure autonomic failure, and dementia with Lewy bodies are characterized by deposition of the protein alpha-synuclein (AS) in autonomic nerves and a high frequency of neurogenic orthostatic hypotension (nOH) due to sympathetic neurocirculatory failure... |
View full abstract
|
Yunden Jinsmaa
Go Top|
3,4-Dihydroxyphenylacetaldehyde-induced protein modifications and their mitigation by N-acetylcysteine |
|
|---|---|
| The catecholaldehyde hypothesis posits that 3,4-dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediary metabolite of dopamine (DA), is an autotoxin that challenges neuronal homeostasis in catecholaminergic neurons. DOPAL toxicity may involve protein modifications, such as oligomerization of alpha-synuclein (AS). Potential interactions between DOPAL and other proteins related to catecholaminergic neurodegeneration, however, have not been systemically explored... |
View full abstract |
Miji Kim
Go Top|
Novel Peptide Released By Eschericia coli Activates Melanocortin Receptor MC1R on Mammalian Cells and Rescues Mice from Death Mediated by Sepsis and Colitis |
|
|---|---|
| MECO-1 (melanocortin-like peptide of E. coli), a novel 33 amino acid peptide isolated from conditioned medium, is identical to the C-terminus of E. coli's elongation factor G (EF-G). MECO-1 has structure and function in mammalian systems that is close to alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropin (ACTH). In vitro, all three peptides at femtomolar concentrations, acting via the mammalian melanocortin-1 receptor (MC1R), potently inhibit cytokine release in response to pro-inflammatory stimuli... |
View full abstract |
Kathryn Luderman
Go Top|
Positive Allosteric Modulators of the D1 Dopamine Receptor Act at Diverse Binding Sites |
|
|---|---|
| The D1 dopamine receptor (D1R) and its signaling is associated with several important neurological processes and neuropsychiatric disorders. Enhancing D1R signaling in the prefrontal cortex is associated with increased cognition and therefore is an appealing treatment strategy for the cognitive decline observed in schizophrenia, Alzheimer?s disease, and other disorders. Because of the clinical liability inherent with D1R agonists, positive allosteric modulators (PAMs) of the D1R have been proposed as an alternative, due to their potential for high selectivity and larger therapeutic windows. Currently, the location and characteristics of potential binding site(s) for allosteric modulators on the D1R are unknown... |
View full abstract |
Amy Moritz
Go Top|
Evidence for a stereoselective mechanism of action for non-competitive antagonism of the D3 dopamine receptor by extended-length bitopic ligands |
|
|---|---|
| Dopamine receptors (DRs) are comprised of two subfamilies based on structure and pharmacology: D1-like (D1R and D5R) and D2-like (D2R, D3R, and D4R). The D3R expression is more restricted to the limbic system, as compared to the D2R, suggesting that modulation of the D3R may be useful for treating substance abuse or psychosis-related disorders without the motor side effects associated with D2R blockade. Extensive structure-activity relationship investigations indicate that D3R-selective antagonists with extended-length structures engage two distinct sites on the receptor. The extended-length ligand?s primary pharmacophore (PP) binds to the orthosteric site whereas the ligand?s secondary pharmacophore (SP) interacts with a unique secondary binding pocket (SBP)... |
View full abstract |
Chiso Nwokafor
Go Top|
Locus Coeruleus Response in Rodent PTSD Model and Reversal of Hyperarousal Symptoms with Intranasal NPY |
|
|---|---|
|
The locus coeruleus (LC) is rapidly activated by stress releasing NE in many diverse brain regions to consolidate information, and adjust arousal, memory acquisition, attention, and vigilance. Alterations in noradrenergic functions are believed to play a key etiological role in development of Post-Traumatic Stress Disorder (PTSD). Patients with PTSD have elevated NE levels in the CSF which is correlated to the severity of PTSD... |
View full abstract |
Alberto Palma
Go Top|
Norepinephrine deficiency in hereditary sensory and autonomic neuropathy type-IV |
|
|---|---|
|
Hereditary sensory and autonomic neuropathy type IV (HSAN-IV) is caused by mutations in the NKTR1 gene. This affects the development of nerve growth factor (NGF)-dependent neurons including sympathetic cholinergic neurons in the skin, causing anhidrosis. Cardiovascular and blood pressure regulation appears normal, but the integrity of sympathetic adrenergic neurons has not been tested... |
View full abstract |
Kayla Schardien
Go Top|
Identification of residues in the fifth transmembrane-spanning domain of the D2-like dopamine receptors that engender signaling bias |
|
|---|---|
| The D2 dopamine (DA) receptor (D2R) signals through a variety of second messenger pathways making it difficult to discern which of these are linked to specific effects of D2R-targeted drugs; however, this complexity provides a unique opportunity to develop pathway-selective therapeutics. Structure-activity analyses using analogs derived from our previously described D2R G protein-biased agonist, MLS1547, coupled with molecular dynamics led to a molecular model for biased signaling which entailed a hydrophobic binding pocket formed by residues I184, F189, and V190 within the fifth transmembrane region (TM5) and second extracellular loop of the D2R... |
View full abstract |
Diana Willmes
Go Top|
The Longevity Gene mINDY (I'm Not Dead, Yet) Affects Blood Pressure Through Sympathoadrenal Mechanisms |
|
|---|---|
|
Reduced expression of the Indy (acronym I'm Not Dead, Yet) gene, coding for a plasma-membrane citrate-transporter, extends life span in several species. Mice with deletion of the mammalian Indy homolog (mIndy, SLC13A5) exhibit beneficial changes in glucose and lipid metabolism akin to caloric restriction, despite normal food intake. Because caloric restriction lowers blood pressure in part through sympathetic inhibition, we hypothesized that mIndy deletion attenuates sympathetic support of blood pressure... |
View full abstract
|
Adrianna Wilson
Go Top|
The b1 and b2 Adrenergic Receptors Exhibit Differential Coupling to the cAMP Sensor NCS-Rapgef2 |
|
|---|---|
|
The beta 1 and beta 2 adrenoceptors (b1 and b2 AR) are GPCRs for the catecholamines norepinephrine and epinephrine. Both of these receptors couple to Gsa. Their activation causes cAMP elevation, which in turn controls cellular signaling through its downstream effectors PKA and the cAMP guanine nucleotide exchange factors (GEFs) Epac1 and Epac2. The b2AR has also been shown to signal via engagement of b-arrestin, which acts as a scaffold for a variety of signaling proteins, including the MAP kinase ERK... |
View full abstract
|
Rebecca Windmueller
Go Top|
Examining discrepancies in proliferative competency between mononucleated and binucleated cardiomyocytes |
|
|---|---|
|
Injury to the myocardium results in loss of cardiomyocytes (CMs). The heart's inability to replace these lost cardiac muscle cells is associated with heart failure. A potential therapeutic strategy would be to assist the heart in regenerating myocardium by reactivating proliferation of endogenous CMs. This has proven challenging, as mammalian CMs appear to lose competency to respond robustly to pro-proliferative stimuli following a neonatal maturation period during which the majority of CMs become binucleated. However, we and others have observed that the small proportion of CMs that remain mononucleated (MoNuc) are substantially more responsive to pro-proliferative stimuli than are binucleated (BiNuc) CMs... |
View full abstract
|
Moussa Youdim
Go Top|
Multi-target neuroprotective and neurorestorative drugs |
|
|---|---|
|
In Parkinson's disease (PD) and Alzheimer's disease (AD) no drugs are available to prevent the neuronal cell loss, and drugs in the clinic have at best symptomatic activity. In both diseases the patients have predisposition to depressive illness, and a significant percentage of PD patients have frontal cortex dementia. Due to the complex etiology of the diseases no "magic bullet" is available to prevent the various cascades of neurotoxic events resulting in neurodegeneration... |
View full abstract
|