Pharmacology Commons^™

P300/Cbp Inhibition With Inobrodib In Combination With Gilteritinib And Venetoclax Targets Leukemia Stem Cells In Epigenetic Mutant Aml, Melanie L. Goetz, Jennifer S. Romer-Seibert, Amanda M. Versace, Scott Kogan, Chetan Jeurkar, Robert L. Bowman, Nigel Brooks, Kris Frese, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and …

Impact Of Statin Medication Use On Glycemic Control And Complications In Type 1 Diabetes, Ryan Bailey

USF Tampa Graduate Theses and Dissertations

Introduction: Hydroxymethylglutaryl-CoA enzyme inhibitors (statins) are frequently used to prevent cardiovascular events in individuals at high risk for cardiovascular diseases, including individuals with diabetes. Prior research has indicated that statins may increase the risk of developing type 2 diabetes (T2D) and may increase hyperglycemia among those previously diagnosed with T2D. To date, little research has investigated the impact of statins on glycemic control and diabetic complications associated with poor glycemic control in those with type 1 diabetes (T1D). The objective of this dissertation is to investigate the association between statin use and measures of glycemic control including hemoglobin A1c (HbA1c), …

Nutrient-Driven Transcription Factor-Dna Interactions And Their Signaling Mechanisms In Metabolic Disease, Evelyn A. Bates

Theses and Dissertations--Nutritional Sciences

Metabolic homeostasis is maintained through tightly coordinated signaling networks that integrate diverse physiological inputs. Central to this regulation are transcription factors, which sense nutrient, hormonal, and vitamin-derived signals and translate them into coordinated gene expression programs. Transcription factor activity is governed by DNA binding, recruitment of coregulatory proteins, and interactions with specific response elements in gene promoters, which allows them to selectively modulate diverse metabolic pathways. Owing to their multifactorial and tunable nature, transcription factors have emerged as promising targets for the treatment and diagnosis of metabolic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). This dissertation explores the molecular …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Exposure To Pm2.5 And Aging., Daniel Chris Gomes

Electronic Theses and Dissertations

Inhalation of fine airborne particulate matter (PM_2.5) is an environmental risk factor for numerous health disorders, including cardiovascular diseases (CVD). While several studies have shown that PM_2.5 exposure can induce oxidative stress, DNA damage, and inflammation, the underlying mechanisms that translate these effects into systemic pathology remain poorly understood. Some recent studies have shown that PM_2.5 exposure can lead to telomere shortening in leukocytes, but the generality of this outcome and contribution to endothelial dysfunction has not yet been fully explored. We hypothesized that PM_2.5inhalation accelerates cellular aging and senescence in both circulating peripheral …

Untangling The Roles Of Pulmonary Vagal Afferent Subsets With Inhaled Irritants, Teresa Darcey

USF Tampa Graduate Theses and Dissertations

The sensory nerves in the airways directly regulate critical defenses and indirectly regulate vital gas exchange. Airway function is largely controlled by the autonomic nervous system, and our understanding of its sensory regulation is directly connected to our ability to treat respiratory and cardiovascular pathologies. Airway sensory afferents are heterogeneous with respect to their electrophysiological properties, peptidergic capacity, and stimuli sensitivity, which at least in part dictate some of their various functions. There is evidence that embryological origin impacts reflex function: activation of the neural crest-derived population of sensory afferents has been shown to evoke the cough reflex whereas activation …

Human Adipose Stem Cell-Derived Small Extracellular Vesicles Modulate Glial Cell Response In Aged And Young Tbi Mouse Models, Salma S. Abdelmaboud

USF Tampa Graduate Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of long-term neurological impairment, with aging significantly increasing vulnerability and worsening outcomes. Older individuals experience greater cognitive and motor deficits after TBI and often show diminished responses to therapeutic interventions. Both aging and TBI independently promote heightened neuroinflammation and cognitive dysfunction, increasing susceptibility to poor recovery. This study investigated the therapeutic potential of small extracellular vesicles (sEVs) derived from human adipose-derived stem cells (hASCs) to promote neurological recovery and modulate neuroinflammation in a mouse model of TBI. Male C57BL/6 mice aged 3, 15, and 20 months underwent controlled cortical impact (CCI) and …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

The Role Of G6pd Variants And 3d Genomic Structure In The Development Of Pulmonary Hypertension, Christina M. Signoretti Ph.D.

NYMC Student Theses and Dissertations

Pulmonary hypertension is an under-recognized global health epidemic which is estimated to affect 1% of the population. It is associated with sustained mean pulmonary artery pressure greater than 20 mmHg, pulmonary artery remodeling, smooth muscle and endothelial cell proliferation and subsequent increased right ventricle hypertrophy due to increased afterload. Glucose-6-phosphate dehydrogenase (G6PD) is one of the key enzymes in the pentose phosphate pathway and has been previously linked to the development of pulmonary hypertension. G6PD deficiency is the most common human enzymopathy which affects approximately 400 million people worldwide and is a result of agricultural and epidemiological evolution in different …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Effects Of Psychedelics On Acute Nicotine Pharmacological Responses, Aleny Oros, Belle Buzzi, Julian Vaughn, Burhan Buttar, Javier Gonzalez-Maeso, M Imad Damaj

IRBEH/Spit for Science Publications and Presentations

Smoking is a major risk factor for illnesses, such as cancers, cardiovascular diseases and respiratory conditions. In smoking, nicotine activates nicotinic acetylcholine receptors in the brain region. Prolonged use of nicotine will desensitize these specific receptors and cause nicotine dependence, resulting in smokers to experience withdrawal symptoms, such as anhedonia, depression, stress, and craving, leading to relapse.2 As the rate cigarette smoking has declined over the years, it is not significantly entitled by the tremendous increase rate of e-cigarette use. In a previous study being published, life-time use of psychedelics is associated with lower nicotine dependence.1

Psychedelics, specifically psilocybin, which …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Enteroendocrine Cell Regulation Of The Gut-Brain Axis, Joshua Barton, Annie Londregan, Tyler Alexander, Ariana Entezari, Manuel Covarrubias, Scott Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Enteroendocrine cells (EECs) are an essential interface between the gut and brain that communicate signals about nutrients, pain, and even information from our microbiome. EECs are hormone-producing cells expressed throughout the gastrointestinal epithelium and have been leveraged by pharmaceuticals like semaglutide (Ozempic, Wegovy), terzepatide (Mounjaro), and retatrutide (Phase 2) for diabetes and weight control, and linaclotide (Linzess) to treat irritable bowel syndrome (IBS) and visceral pain. This review focuses on role of intestinal EECs to communicate signals from the gut lumen to the brain. Canonically, EECs communicate information about the intestinal environment through a variety of hormones, dividing EECs into …

Gpr75 Deficiency Attenuates High Fat Diet-Driven Obesity And Glucose Intolerance, Sakib Hossain

NYMC Student Theses and Dissertations

Recently, a collaboration between Regeneron Pharmaceuticals and the Schwartzman-Garcia labs at New York Medical College published an exome sequencing study of individuals across the United Kingdom, United States, and Mexico which concluded that individuals possessing non-functioning, truncated mutations to the orphan g protein coupled receptor (GPCR), GPR75, had lower BMI and 54% reduced likelihood of obesity. The present study was undertaken to fully characterize the metabolic phenotype of Gpr75 deficient mice when fed a high fat diet (HFD) and explore potential mechanisms by which GPR75 activation links to increased adiposity and decreased glucose tolerance. After 14 weeks of HFD-feeding we …

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin

Dataset For Manuscript: Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Silas J. Leavesley

BioImaging and BioSystems Research

The dataset contains raw and processed hyperspectral timelapse image data that are described in the manuscript:

Parker, M., Annamdevula, N. S., Pleshinger, D., Ijaz, Z., Jalkh, J., Penn, R., Deshpande, D., Rich, T. C. & Leavesley, S. J. Comparing Performance of Spectral Image Analysis Approaches for Detection of Cellular Signals in Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy. Bioengineering 10, 642 (2023).

Age-Associated Increase Of Gamma Delta T Cells In Visceral Adipose Tissue And Mechanisms Of Their Accumulation, Sujata Mukherjee

Theses and Dissertations--Pharmacology and Nutritional Sciences

Chronic systemic inflammation, known as inflammaging is considered a hallmark of aging and associated diseases. While adipose tissue has long been considered only as a caloric reservoir regulating systemic energy homeostasis, research in the past couple of decades substantiate its endocrine function to secrete an array of inflammatory mediators and hormones, which have physiological effects on multiple organ systems, and contribute to inflammaging. Redistribution of adipose tissue from subcutaneous to visceral depots, changes in the immune profile and the chronic inflammatory state are among the major sources of adipose tissue dysfunction with aging.

This dissertation is focused on identifying and …

Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez

Pharmaceutical Sciences (PhD) Dissertations

Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …

Building Tools For Improved Modulation Of The Human Gabaa Receptor, A Central Nervous System Target For The Treatment Of Anxiety, Garrett Edward Zinck

Theses and Dissertations--Pharmacy

In the U.S., anxiety is recognized as an increasing range of mentally and physically debilitating psychiatric health disorders with significant economic repercussions. Over the last 20 years, several novel anti-anxiety therapies have entered the drug development pipeline, but none have made it to market.

The work in this dissertation focused on structurally modifying valerenic acid (VA), a structurally unique carboxylated sesquiterpene acid found in Valeriana officinalis. VA is putatively reported to have allosteric modulatory activity of the human GABA_A receptor, a ligand-gated ion channel responsible for attenuating neurotransmissions. Structural modeling of VA’s GABA_A receptor interaction suggests that …

Effects Of Exogenous Ketone Therapy On Performance, Cardiorespiration, And Seizure Genesis During Exposure To Hbo2 In The Sprague Dawley Rat, Nicole M. Stavitzski

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is used for clinical HBO2 therapy and in undersea and aerospace medicine. HBO2 is a humanmade extreme environment and protracted exposures can cause several adverse physiological effects on the body. For example, HBO2 increases the partial pressure of oxygen (PO2) in the body leading to redox stress. Redox stress is, in part, a cause of oxygen toxicity that manifests as seizures in its most severe form (central nervous system oxygen toxicity, CNS-OT). This dissertation focuses on strategies to be employed specifically for the warfighter breathing HBO2. Currently, the only way to prevent CNS-OT is to lower the …

Race And Drug Toxicity: A Study Of Three Cardiovascular Drugs With Strong Pharmacogenetic Recommendations., Travis J. O'Brien, Kevin Fenton, Alfateh Sidahmed, April Barbour, Arthur F Harralson

Pharmacology and Physiology Faculty Publications

No abstract provided.

Mitigation Strategies For Central Nervous System Oxygen Toxicity In Rodents: Ketone Metabolic Therapy And Mitochondrial Antioxidant Therapy, Christopher Manuel Hinojo

USF Tampa Graduate Theses and Dissertations

Hyperbaric oxygen (HBO2) is a frequently encountered condition in undersea medicine and hyperbaric oxygen therapy (HBOT). The risk of CNS oxygen toxicity (CNS-OT) seizures limits its use in hyperbaric medicine and limits bottom time for diving operations. In this study, we sought to understand the role of reactive oxygen species (ROS) in two mitigation strategies for CNS-OT; ketone metabolic therapy (KMT), which is known to delay onset of CNS-OT seizures, and mitochondria targeted antioxidant therapy (MitoTAT), which has never been tested under HBO2 conditions. We specifically focused on superoxide anions, one of the early reduction products of molecular oxygen, and …

A Study Of Trpa1 Activation Via Covalent Electrophilic Modification Of Cysteines, Thomas A. Parks

USF Tampa Graduate Theses and Dissertations

A subset of sensory nerves called nociceptors are stimulated by noxious stimuli and evoke nocifensive responses in different organ systems. Transient Receptor Potential Ankyrin 1 (TRPA1) is a tetrameric, nonselective, cation channel that initiates the generator potential that evokes afferent signaling in nociceptive nerves. TRPA1 is activated many harmful irritants, such as food chemicals, environmental pollutants, reactive oxygen species and other endogenous mediators. Most TRPA1 agonists have electrophilic properties, which covalently modify cysteine residues on the cytosolic side of the channel. Biochemical studies in our lab have identified four cysteines (C273, C621, C665, C1085) that rapidly bound iodoacetamide (irreversible electrophile); …

Morphological Changes In Dorsal Root Ganglia Macrophages Associated With Neuropathic Pain Mechanisms Suggest A Novel Target For Chronic Pain Therapy, Emily Kussick

CMC Senior Theses

The present study examined morphological changes in the dorsal root ganglia (DRG) following an innate immune stimulus. The importance of the DRG has increasingly become recognized in pain processing as more than just the home of primary afferent cell bodies. All sensory information passes through the DRG via the primary afferents, and on to the spinal cord. The primary afferents synapse with second-order neurons in the spinal cord that ascend towards the brain, where they transmit the pain signal to the limbic forebrain and/or the somatosensory cortex for processing. The DRG is an interesting niche to study at as it …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Functional Significance Of Endothelial Sigma-1 Receptors In Vascular Reactivity And Barrier Function, Zeinab Y. Motawe

USF Tampa Graduate Theses and Dissertations

The sigma-1 receptor (σ1) is a single 25 kD polypeptide that acts as a chaperone protein residing primarily in the endoplasmic reticulum Its interaction with mitochondria at the mitochondria-associated ER membrane domain is well-documented. Following activation, σ1 binds to the inositol trisphosphate receptor (Hayashi & Su), and modulates intracellular calcium homeostasis. Also, the activated σ1 modulates plasma membrane receptors and ion channel functions, and may regulate cellular excitability. Further, σ1 affects trafficking of lipids and proteins essential for neurotransmission, cell growth and motility. Activation of σ1 provides neuroprotection and cardio-protection in various models. Examples of neuroprotection include but not limited …