Pharmacology
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Molecular interactions and signaling mechanisms of the oncogenic fusion protein DNAJ-PKAc in fibrolamellar carcinoma
The DNAJ-PKAc fusion kinase is a defining feature of the adolescent liver cancer fibrolamellar carcinoma (FLC). A single lesion on chromosome 19 generates this mutant kinase by creating a fused gene encoding the chaperone ... -
Stimulus-Dependent Regulation of 2-Arachidonoyl Glycerol Signaling and the Mechanism of its Hydrolysis by ABHD6
Cannabis has been used for thousands of years for recreational and therapeutic effects. The efficacy of medicinal cannabis for conditions such as epilepsy and pain has resulted in the discovery of the molecular targets of ... -
Novel tools for multi-omic characterization of subnuclear RNA-scaffolded structures in development and disease
RNA molecules are increasingly recognized as fundamental regulators of subcellular organization. In the nucleus, RNAs scaffold numerous structures that mediate diverse and essential genomic functions. These range from ... -
Development of Oligonucleotide-directed proximity-interactome MAPping (O-MAP), for characterizing RNA-protein interactions and higher order subnuclear architecture in situ
RNA-protein interactions underscore a broad array of regulatory mechanisms throughout biology, and dysregulation of these interactions contributes to a broad range of human pathologies such as neurodegenerative disorders ... -
Mechanisms and physiological implications of mitochondrial and cellular calcium signaling
Calcium signaling is central to fields as disparate as memory formation, protein structure, and cellular migration. The five chapters of this dissertation each examine calcium signaling in a different context. First, an ... -
Uncovering the Role of Protein Kinase TAOK2 as an Endoplasmic Reticulum-Microtubule Tether
Kinase signaling drives a multitude of components of neuronal development such as establishment of polarity, dendritic growth and arborization, dendritic spine formation, and synaptogenesis. Thousand And One amino acid ... -
The Structure of Sperm Autoantigenic Protein (SPA17): An R2D2 Protein Critical to Cilia and Implicated in Oncogenesis
A-Kinase Anchoring proteins (AKAPs) localize the activity of cyclic AMP (cAMP)-Dependent Protein Kinase (PKA) through interaction of an amphipathic helix that binds to a conserved RIIα docking and dimerization (R2D2) domain ... -
Adrenergic Regulation of Cardiac CaV1.2 via Direct Phosphorylation and the GTPase RAD
Dysregulation of the cardiac fight-or-flight response has been linked to chronic heart failure and arrhythmic disorders. The L-type calcium channel CaV1.2 has a central role in mediating the cardiac fight-or-flight response, ... -
Serotonergic Circuits Mediating Stress Potentiation of Addiction Risk
Stress-induced release of dynorphins (Dyn) activates kappa opioid receptors (KOR) in monoaminergic neurons to produce dysphoria and potentiate drug reward; however, the circuit mechanisms responsible for this effect are ... -
Identifying the Mechanisms Behind Radiation Resistance in Treatment Naïve Diffuse Intrinsic Pontine Glioma Models
Diffuse Intrinsic Pontine Glioma (DIPG) is a near universally fatal pediatric brain tumor that occurs in the pons and other midline structures. These tumors are characterized by the presence of a unique histone mutation: ... -
Targeting an anchored phosphatase-deacetylase unit restores renal ciliary homeostasis
In the kidney, primary cilia projecting into the lumen of cells lining the inner medullary-collecting duct bend with urine flow to initiate intracellular signaling events. This mechano-sensory apparatus is defective in ... -
The role of the central amygdala kappa opioid receptor and dopamine in discriminatory fear learning and anxiety
Collectively, anxiety disorders are the most common mental illness in the U.S., with about 30% of Americans experiencing this disorder in their lifetime. There are a variety of anxiety disorders, including phobias, obsessive ... -
Decoding protein kinase signaling during mitosis: Exploiting molecular scaffolds and developing drug-targeting tools for studying local kinase biology
Fundamental cellular processes such as cell division, migration, differentiation, and growth require environmental signals to be converted into chemical responses that generate biological outputs. Accordingly, these events ... -
Social Transmission of a Stress-Related Neuroadaptation
Stress is highly pervasive in humans, impacting motivated behaviors with an enormous toll on life quality. Many of the effects of stress are orchestrated by neuropeptides such as corticotropin-releasing factor (CRF). It ... -
Elucidating the role of unique structural features of the α1D-adrenergic receptor: A tale of two tails
G protein-coupled receptors (GPCRs) are seven transmembrane domain proteins accounting for ~4% of the human genome, and the predicted target of ~30% FDA approved therapeutics. Often, drugs compete with endogenous ligands ... -
Development of analytical tools to enrich and identify protein dopaminylation
Dopamine homeostasis and oxidative stress are thought to be key players in the etiology of Parkinson’s disease (PD). PD is a disorder characterized by the death of dopaminergic neurons in the substantia nigra and the ... -
The Role of KLHDC2 in Recognizing Diglycine C-end Degron and its Therapeutic Potential
Ubiquitin-proteasome system is crucial for controlling essential cellular processes. Eukaryotic cells conjugate the eight kDa ubiquitin polypeptide to a variety of proteins to regulate their functions or turnover. Modification ... -
Broadband Tuning the Voltage Dependence of a Sodium Channel
Mammalian voltage-gated sodium channels are comprised of four homologous domains, each containing a functionally distinct voltage-sensing domain (VSD). In contrast, the bacterial sodium channel NaVAb is a homotetramer, ... -
Combinatorial strategies using CRISPR/Cas9 for gene mutagenesis in adult mice
A major challenge to understanding how genes modulate complex behaviors is the inability to restrict genetic manipulations to defined cell populations or circuits. To circumvent this, we created a simple strategy for ... -
Investigating the role of a CaV2.1 - Syt7 interaction in Short-term Synaptic Facilitation
Synaptic facilitation is the enhancement of successive transmissions between neurons over timespans of less than a second. It is a form of synaptic plasticity which has long been observed, yet its molecular mechanisms ...