Contributions to Science
"Research is formalized curiosity. It is poking and prying with a purpose."
PREBACCALAUREATE RESEARCH
I studied how the chemical element, molybdenum (Mo), binds to organic compounds (amino acids).
The first opportunity I had to conduct research was through a summer program, the Quality Education for Minorities Network/National Aeronautics and Space Administration (NASA) SHARP Plus Program, at Norfolk State University. Through this science and engineering apprenticeship program, I conducted research in the Department of Chemistry. My scientific study was concentrated in the physical sciences. It centered on investigating the bonding structure between molybdenum in oxidation state six and amino acid type ligands. Many enzymes that interact with molybdenum play several important roles in animal metabolism. Such molybdo-enzymes are xanthine oxidase and xanthine dehydrogenase, which both catalyze the oxidation of xanthine to uric acid, a key step in purine metabolism. The importance of investigating molybdenum was due to its relation to the disease, gout, which has a hallmark characteristic of excessive production of uric acid.
Concerning the production of gout in humans, the research that I conducted aimed to provide new ways of finding how molybdenum’s involvement in the development of gout could prevent the disease from spreading. Thus, in this investigation, I identified the molybdenum-oxygen core in several new amino acid type complexes. By obtaining the bonding structure between molybdenum (VI) and several ligands, such as ethylenediamine diacetic acid (EDDA), I was able to determine whether the ligand was bound to the Mo(VI)-L complex. I accomplished this by taking the spectra of Mo(VI) and Mo(VI)-L complexes and determining whether the amino acid type ligands had definite positions of bonding observed from the infrared spectrum.
PREBACCALAUREATE RESEARCH
I studied how herbal supplements, saw palmetto and licorice root, can potentially be used as a treatment for prostate cancer.
As an undergraduate, another opportunity to quench my passion for science occurred at Xavier University of Louisiana. Through an undergraduate research course, I conducted research in the area of biochemistry. The research focused on prostate cancer, a slow-growing heterogeneous tumor primarily of prostate epithelium cell origin. This investigation was important due to the impact prostate cancer has had on the male population over the age of 50 in the United States. Prostate cancer is the most common form of cancer, other than skin cancer, among men in the United States and is the second only to lung cancer as a cause of cancer-related death among men. It can progress from a benign hormone-sensitive to a malignant hormone-insensitive phenotype. This research project was also essential since many treatment options have several disadvantages. Consequently, alternative treatment strategies that are more effective and comfortable are in great demand (i.e., use of herbal supplements).
The objectives of the research were as follows: (1) to test the effects of over-the-counter supplements on prostate carcinoma cell lines, DU145, and (2) to evaluate the expression of specific proteins in treated and untreated DU145 cells. The scientific investigation I conducted attempted to provide a qualitative analysis of protein expression in DU145 cells and identify specific proteins via protein extraction and western blot analysis. The DU145 cells were pretreated with varying concentrations of herbal supplements, saw palmetto and licorice root, in cell culture. This enabled me to determine whether herbal supplements could inhibit cellular proliferation in a dose dependent manner.
PREBACCALAUREATE RESEARCH
I studied similarities and differences in how foreign chemicals are removed from the body once consumed (xenobiotic metabolism) between humans, shellfish, and fish to understand health risks when humans consume shellfish and fish contaminated with cancer-causing chemicals.
As an undergraduate, I also conducted research at
Tulane University School of Public Health and Tropical Medicine in the Department of Global Environmental Health Sciences through the Louis Stokes Louisiana Alliance for Minority Participation (LS-LAMP) program. The LS-LAMP is a nationwide National Science Foundation alliance program aimed at increasing the number and quality of minority students enrolling in and completing baccalaureate degrees in science, technology, engineering, and mathematics (STEM) and subsequently going on to pursue graduate studies in STEM disciplines. As a LS-LAMP participant, I compared xenobiotic metabolism mechanisms between humans and freshwater organisms, like crayfish and fish. I used high performance liquid chromatography to separate volatile organic compound and heavy metal concentrations from tissue samples of shellfish species (i.e., blue crab, Callinectes sapidus, crayfish, Procambarus acutis, and river shrimp, Macrobrachium ohionii) and several fish species (i.e., blue catfish Ictalurus furcatus, smallmouth buffalo Ictiobus bubalus and white bass Morone chrysops). These chemicals were then individually detected and their concentrations were measured using atomic absorption spectrometry. The freshwater organisms were collected along the lower Mississippi River from the Louisiana–Arkansas border to the Gulf of Mexico by the Louisiana Department of Environmental Quality, Office of Water Resources in coordination with the US Environmental Protection Agency. The findings from this study were used to determine the degree of human health risks (i.e., cancer and non-cancer risks) associated with consuming fish and crustaceans harvested from the Mississippi River that were contaminated with Mississippi River Toxics Inventory Project (MRTIP) chemicals at elevated levels or levels known to pose health risks to humans.
PREBACCALAUREATE RESEARCH
I studied how to create maps from geographic and census data to revitalize a New Orleans, Louisiana community.
Furthermore, as an undergraduate, I conducted research through an Urban Technical Assistance Project (UTAP) internship that was sponsored by Columbia University. I performed physical surveys and used geographic information systems (GIS) to assist staff and local government planning efforts related to community development of blighted and abandoned housing and other infrastructures in a local community known as Gert Town. I as well conducted research on census data for the neighborhood and extracted information from large census data sets for research purposes. Moreover, I provided urban planning technical assistance for the community’s revitalization and housing development strategy, including town hall meetings and planning workshops.
PREMASTERS RESEARCH
I studied how drugs that are currently being used to treat kidney, liver, and thyroid cancer (i.e., raf inhibitors, such as sorafenib) can potentially be used to improve memory problems in people that suffer from Alzheimer’s disease.
My early publications concerned research on Alzheimer’s disease (AD) pathology and therapeutics that I conducted at Bay Pines Veterans Affairs Healthcare System. The active form of the enzyme, serine/threonine kinase cRaf-1, is increased postmortem in the brains of AD patients and in transgenic mouse models of AD pathology. The persistent activation of cRaf-1 has been shown to activate the proinflammatory transcription factor NFkappaB and, consequently, increase the expression of its downstream targets, such as the amyloid precursor protein (APP), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). I investigated the molecular mechanisms of the activity of Raf inhibitors in embryonic rat cortical neurons exposed to amyloid beta (Abeta) toxicity and in a mouse model of early-onset AD (APPswe). The mouse model carried a transgene that coded for the 695-amino acid isoform of the human Alzheimer Abeta precursor protein, which was derived from a Swedish family with early-onset AD. APPswe mice, thus, expressed high levels of the mutant Abeta peptide, developed amyloid plaques, and exhibited memory deficits similar to that found in humans with AD.
Through this research, I cultured embryonic rat cortical cells exposed to Aβ1-42 oligomers in the presence or absence of the cRaf-1 inhibitors, GW5074 or ZM336372. After drug treatment, I quantified cell viability using the MTT assay and measured changes in NFkappaB protein expression by Western blot. Changes in protein expression of NFkappaB and its downstream targets by Western blot was also measured in different brain regions (e.g., the hippocampus, cortex, and striatum) of APPswe mice treated with the Raf inhibitor, Sorafenib. The findings from this research suggested that cRaf-1 inhibitors are neuroprotective against neurotoxic insults, such as the Abeta peptide, in vitro, through a mechanism that involves NFkappaB. It also suggested that cRaf-1 inhibitors can reverse memory impairment and reduce the expression of APP, COX-2, and iNOS in the brains of a transgenic mouse model of AD. The findings from this research demonstrated how Raf inhibitors can serve as promising therapeutic tools against neurological disorders and as anti-neurodegenerative agents.
Echeverria, V, Burgess, S, Gamble-George, J, Arendash, GW, Citron, BA. (2008). Raf inhibition protects cortical cells against β-amyloid toxicity. Neuroscience Letters, 444: 92-96. PMID: 18706973.
Echeverria, V., Burgess, S., Gamble-George, J., Zeitlin, R., Lin, X., Cao, C., Arendash, G.W. (2009). Sorafenib inhibits nuclear factor kappa B, decreases inducible nitric oxide synthase, and cyclooxygenase-2 expression, and restores working memory in APPswe mice. Neuroscience, 162(4):1220-1231. PMID: 19447162.
POSTMASTERS RESEARCH
I studied how methamphetamine, a very addictive stimulant drug, damages cells in the brain (neurons) and negatively affects memory.
Moreover, I published research on neurotoxicity due to subchronic methamphetamine (METH) exposure at Meharry Medical College. METH is the second most widely used illicit drug worldwide and is abused by drug addicts in high concentrations for long periods of time. Current reports in the literature suggest that METH-induced neuronal injury may render METH users more susceptible to neurodegenerative pathologies. Specifically, chronic exposure to psychostimulants is associated with decreases in striatal dopamine transporter (DAT) expression and increases in striatal alpha-synuclein expression, a synaptic protein implicated in the pathogenesis of neurodegenerative diseases. This raises the question whether METH exposure causes memory deficits and affects protein levels in the brain that play a key role in dopaminergic neurotransmission. I investigated the memory and molecular effects of subchronic METH administration in C57BL/6J mice.
To do this, I examined changes in short-term and spatial memory using the novel object recognition and novel spatial recognition tasks and measured changes in the expression of specific protein markers involved in dopaminergic homeostasis, specifically alpha-synuclein, tyrosine hydroxylase, and DAT, in different brain regions of mice after METH treatment by Western blot analyses. This research suggested that subchronic METH exposure causes spatial memory deficits. It also showed that subchronic METH exposure causes differential, brain specific expression of protein markers involved in dopaminergic homeostasis, which could be one of the causal mechanisms or compensatory consequences of METH-mediated neurotoxicity. The results from this research will potentially further the discovery of molecular targets that can be used to prevent or treat neurodegeneration caused by METH exposure.
Swant, J., Goodwin, J.S., North, A., Ali, A.A., Gamble-George, J., Chirwa, S., and Khoshbouei, H. (2011). α-Synuclein stimulates a dopamine transporter-dependent chloride current and modulates the activity of the transporter. Journal of Biological Chemistry, 286(51):43933-43. PMID: 21990355.
North, A., Swant, J., Salvatore, M.F., Gamble-George, J., Prins, P., Butler, B., Mittal, M.K., Heltsley, R., Clark, J.T., Khoshbouei, H. (2013). Chronic methamphetamine exposure produces a delayed, long-lasting memory deficit. Synapse, 67(5):245-57. PMID: 23280858.
PREDOCTORAL RESEARCH
I studied how drugs can be used to change the levels of chemicals in brain cells (neurotransmitters, such as endocannabinoids) and potentially treat anxiety, depression, and behaviors created by exposure to stress.
At Vanderbilt University School of Medicine, I published research on the role of the endocannabinoid (eCB) system in stress-induced behavioral and synaptic maladaptations in mice. Cannabinoid receptors have been examined as potential targets to alleviate the negative consequences of anxiety, trauma-related, and stress-related disorders. However, in preclinical animal studies, synthetic cannabinoids can produce adverse motoric and cognitive effects. Thus, these studies examined how augmenting eCB levels in the brain through use of inhibitors of eCB degradative enzymes have the potential for combating anxiety and stress responses. In particular, my dissertation research project tested the hypothesis that substrate-selective inhibitors of cyclooxygenase-2 (SSIs-COX-2) can counteract stress-induced anxiety-like behaviors by elevating anandamide levels in the brains of animals, resulting in enhanced eCB signaling through cannabinoid receptors.
This research involved devising a rodent model of acute and chronic stress-induced anxiety and the use of electrophysiological recordings in coronal brain slices to examine changes in neuronal activity and biochemical techniques to measure eCB levels in the brain. Through these studies, the SSIs-COX-2, LM-4131 and lumiracoxib, and the selective COX-2 inhibitor, celecoxib, reduced anxiety-like behaviors in mice subjected to stress. The anxiolytic action of the SSIs-COX-2 was mediated through the small conductance calcium-activated potassium channels when mice were subjected to stress and caused a decrease in excitatory cell firing in the amygdala. These findings will hopefully provide more knowledge on how the role of the eCB system in anxiety, trauma-related, and stressor-related disorders can be useful for medical practice, especially with respect to treating individuals that suffer from these disorders.
Gamble-George, J., Conger, J., Hartley, N., Gupta, P., Sumislawski, J.J., and Patel, S. (2013). Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice. Psychopharmacology (Berl), 228(3):401-9. PMID: 23483200.
Hermanson, D. J., Hartley, N. D., Gamble-George, J., Brown, N., Shonesy, B. C., Kingsley, P. K., Colbran, R. J., Reese, J., Marnett, L. J., and Patel, S. (2013). Substrate-selective inhibition of COX-2 enhances central endocannabinoid signaling. Nature Neuroscience, 16(9):1291-8. PMID: 23912944.
Bluett, R.J.*, Gamble-George, J.C.*, Hermanson, D. J., Hartley, N.D., Marnett, L. J., and Patel, S. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation. Translational Psychiatry (2014), 4:e408. doi: 10.1038/tp.2014.53. PMID: 25004388. *These authors contributed equally to the manuscript.
Gamble-George, J.C., Baldi, R., Halladay, L., Kocharian, A., Hartley, N., Silva, C.G., Roberts, H., Haymer, A., Marnett, L.J., Holmes, A., and Patel, S. Cyclooxygenase-2 inhibition reduces stress-induced affective pathology. eLife (2016), 5:e14137. PMID: 27162170.
POSTDOCTORAL RESEARCH
I studied how a protein (Tat) that plays a role in making more copies (replication) of an infectious agent, the human immunodeficiency virus type 1 (HIV-1), damages brain cells after exposure to methamphetamine, a very addictive stimulant drug.
At the University of Florida, I had the opportunity to expand my technical, philosophical, and research expertise in the neuroscience field to examine the cellular mechanisms of drug addiction and HIV-1 infection. Many METH abusers are HIV-1 positive. Combined HIV and METH insults can worsen brain injury and, subsequently, lead to neurocognitive impairments known as HIV-associated neurocognitive disorders (HAND). HAND is advanced by several factors, including the presence of the HIV-1 Tat protein in the brain. In particular, my postdoctoral research project focused on how the HIV-1 Tat protein induces cellular toxicity and affects ion channel activity and function in dopaminergic neurons and other cell types derived from the ventral tegmental area (VTA) and the substantia nigra (SN) before and after methamphetamine (METH) exposure. The findings from this research project will potentially provide new key insights into pharmacological strategies for the treatment of drug addiction and HIV-1 infection.
Miller, D.R., Shaerzadeh, F., Phan, L., Sharif, N., Gamble-George, J., McLaughlin, J.P., Streit, W.J., and Khoshbouei, H. HIV-1 Tat regulation of dopamine transmission and microglial reactivity is brain region specific. Glia (2018), 00:1-14. doi: 10.1002/glia.23447. PMID: 29733459.
Gaskill, P.J., Miller, D.R., Gamble-George, J., Yano, H., and Khoshbouei, H. HIV, Tat and dopamine transmission. Neurobiology of Disease (2017), 105:51-73. doi: 10.1016/j.nbd.2017.04.015. PMID: 28457951.
POSTDOCTORAL RESEARCH
I studied how interactions between an individual’s genes and their social environment contribute to substance misuse, mental health problems, and other health risk behaviors.
As a postdoctoral fellow at New York University, my research focuses on the biopsychosocial factors that contribute to substance misuse, HIV/Hepatitis C virus (HCV) risk behaviors, mental health problems, and other health risk behaviors in adolescents and adults. I am leading an exploratory study on the decision processes that adult opioid users make to seek or avoid illicit fentanyl-adulterated drugs and the factors, including social support, capital, and connectedness, that influence these decision-making processes as well as their relation to injection risk behaviors, which are both major issues during the opioid and COVID epidemics. I am also examining changes in volumetric brain composition because of genetic variants linked to affective pathologies, substance use, and early life adversity in adopted children followed into adulthood. Furthermore, I am studying the contextual factors that influence drug initiation among young adults from the Soviet Union now living in New York City who were active opioid users and/or in treatment for opioid use disorder.
Opara, I., Malik, S., Lardier, D.T., Gamble-George, J., Kelly, R.J., Okafor, C.N., Greene, R.N., and Parisi, D. Alcohol Use Cravings as a Mediator Between Associated Risk Factors on Increased Alcohol Use among Youth Adults in New York During the COVID-19 Pandemic. Alcoholism Treatment Quarterly (2021), 39(4):415-429. doi: 10.1080/07347324.2021.1950091.
Ransome, Y., Hayashi, K., Gamble-George, J., Dean, L.T., and Villalonga-Olives, E. Racial and ethnic differences in the association of social cohesion and social capital with HIV testing. SSM – Population Health (2023), 21:101327. doi: 10.1016/j.ssmph.2022.101327.
Complete List of Published Work in MyBibliography:
https://www.ncbi.nlm.nih.gov/myncbi/joyonna.gamble-george.1/bibliography/public/
ORCID: orcid.org/0000-0002-5492-9216
Scopus Author ID: 24729181300
Web of Knowledge Researcher ID: Q-2075-2017, http://www.researcherid.com/rid/Q-2075-2017
Loop: 1357293
Bibliometrics:
Web of Science ISI H-index = 9 (Times cited = 322, Average citations per item = 20.12, Items = 16, Peak citation year 2016 = 93; 27 September 2017, http://apps.webofknowledge.com).
Google Scholar H-index = 13 (Times cited = 1214; January 2023, https://scholar.google.com/citations?user=AL0vjU8AAAAJ&hl=en).