Summer 2023 Research Internship

Permanent URI for this collection

http://hdl.handle.net/1920/13586

These papers are published as part of the Center for Biomedical Science and Policy (CBSP) Young Scholars Research Internship completed during Summer 2023. The program mentored elite high school and undergraduate students interested in pursuing study and/or career in the fields of biology or medical science with emphasis on advanced data analytics.

Browse

Now showing 1 - 7 of 7

Project 1: Racial & Sex Disparities in Lupus & Transplant Outcomes
(George Mason University, 2023-08) Endlaw, Shriya; Farhan, Hamza; Peng, Candice; Tan, Alexander; Koizumi, Naoru
Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with both high morbidity and mortality rates [1]. Clinical symptoms, laboratory findings, and optional biopsy results are the basis for early diagnosis of SLE. The disease is well-known for its butterfly rash that appears mainly on women at child bearing ages, and patients should be treated with antimalarials with hydroxychloroquine presenting the best results; it has a higher rate of remission, fewer relapses and reduced damage in the course of the disease [2]. Although there has been significant progress made in regards to SLE, the number of SLE patients who face End Stage Renal Disease (ESRD) has increased from 1.6 to 4.9 million from 1982 to 2004 [3]. Patients with ESRD were tested to predict a 3-year allograft survival after transplantation. Graft has an 84% chance of 3-year survival if the patient didn’t need dialysis during the first week compared to 58% if dialysis was needed during the first post transplantation week. For those who had needed dialysis for the first week, if their maintenance immunosuppressive regimen contained prednisone, took hemodialysis, and was older than 50 years, their graft had a lower probability of survival [1]. Adding on, much advancement and findings regarding SLE has led to the discovery of correlation between the disease and minority populations. The Centers for Disease Control and Prevention National Lupus Registries found that people of color (African Americans, APIs, and Hispanics) are more susceptible to SLE. Studies show that psychosocial stressors are potential exacerbators of SLE which can activate the inflammatory pathways. Often exposed to racial discrimination, people of color experience a large source of stress which can cause many health disparities, which in turn, can lead to the further worsening of SLE [4]. It has also been studied that after a kidney transplant, many patients have gotten rid of their Lupus while others, specifically African Americans (AA) have gotten Lupus back with other symptoms [3]. Adding on, five years after a kidney transplant for Lupus Nephritis (LN) graft survival for AF is at 63%, while for non-AA the graft survival rate is at 78.3%. Further, AA of lower median household income (MHI) are more likely to experience quicker graft loss compared to AA of higher MHI. For non-AA, there was no significant trend between MHI and graft loss [5]. While LN significantly increased the risk of graft failure, rejection remained the primary driver of graft failure incidence. These results emphasized that these findings should not discourage patients with Lupus from considering a kidney transplant [6]. Objective: The study investigated how the outcomes of kidney transplants differ by sex and race in the transplant recipients with SLE diagnosis.
Project 2: Optimal Immunosuppressive Regimen for Pediatric Liver Transplant Recipients
(George Mason University, 2023-08) Ashok, Keshav; Gottumukkala, Ananya; Panesar, Meher; Song, Jessika (Jiayao); Koizumi, Naoru
Background: The main obstacle to success is transplant rejection and managing the side effects of immunosuppressive medications. Induction and maintenance types of immunosuppressive medications are used in transplants. Induction therapy is used temporarily, only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. Maintenance therapy can involve the use of antibodies or higher doses of medications. The standard triple medication regimen usually consists of the combination of a calcineurin inhibitor, an antiproliferative agent and a corticosteroid. These have been found to be more effective in balancing the risks of suppressed immune system with the benefit of organ transplant. However, the immunological risks (driven by age, preconditions, and other factors) of the child/pediatric patient should be considered, and the immunosuppressive therapy should be followed by therapeutic drug monitoring. [1] A study conducted by Feng, Ekong & Lobritto (2012) reported that immunosuppression came with many toxic effects. Some of these include renal dysfunction, infection, metabolic perturbation, and malignancy [2]. To add on, Blondet, Healy & Hsu (2017) reported that the 2 most common immunosuppressants, tacrolimus and cyclosporine, were both known to have long-term side effects in children, which included nephrotoxicity, neurotoxicity, infection, and malignancy. Patient survival rates for pediatric liver transplant recipients after the use of immunosuppressive agents were 94% after one year, 91% after five years, and 88% after 10 years [3]. They also found that the side effects of immunosuppressive medications were severe in pediatric liver transplant recipients. Some immunosuppressive agents, such as tacrolimus, antithymocyte globulin, basiliximab, and others, might cause side effects including sensitivity, nausea, vomiting, diarrhea, high blood pressure, acne, abdominal pain, discomfort, mood swings and more. While immunosuppressants help with preventing rejection, it may be a challenge for pediatric patients since their reactions to the medications may be critical. Objective: The study investigated how transplant outcomes (graft failure and patient mortality) vary by induction immunosuppressive therapy among pediatric liver transplant recipients.
Project 3: Geographical and Familial Factors in Engagement of Advance Directives
(George Mason University, 2023-08) Li, Jessie; Liu, Tyler; Nokta, Nyla; Shah, Ahaan; Wang, Arthur; Inoue, Megumi
Background: Multiple studies have investigated the factors influencing the completion of Advance Care Planning (ACP) in the United States of America [1][2]. ACP involves preparing and discussing future medical care when the patient is incapacitated in some way so that they retain some autonomy of their decisions even when they are unable to communicate effectively [3][4]. Previous studies have compared rural and urban nursing home residents and found that rural nursing home residents were more likely to have advance directives in place and less likely to experience extended hospitalizations or intensive care stays compared to their urban counterparts [5]. Between urban and rural patients with Physician Orders for Life-Sustaining Treatment forms, orders for full treatment are less prevalent among rural patients, with a preference towards DNR and limited intervention [6]. However, the findings on rural vs. urban are not consistent. Another line of research has examined racial disparities, revealing that White/non-Hispanic residents were over twice as likely as Black residents to have documented advance directives, with county-facility characteristics accounting for a significant portion of this difference. Additionally, regional variations in Medicare spending have been linked to higher rates of ACP engagement [7][8]. Positive interactions, emotional support, and encouragement from family members play significant roles in motivating patients to undertake ACP [2][9] leading to more appropriate care during their end-of-life phase. Conversely, strained relationships characterized by criticism or lack of support may discourage individuals from engaging in ACP. Objective: The objective of this study was to determine the influence of geographical and familial factors on advance directive (AD) engagement in the United States.
Project 4: Gut Microbiome and Kidney Transplant
(George Mason University, 2023-08) Cho, Minseo; Herdrich, Kyle; Jung, Isaac; Liu, Jiahui; Li, Meng-Hao
Background: The gut microbiota, comprising the entire population of microorganisms that colonize the colon, has evolved over time to establish a symbiotic relationship with the human body, yielding mutual benefits [1]. This microbiome plays a pivotal role in critical bodily functions, including biosynthesis, short-chain fatty acid (SCFA) production, gut regulation, and immune system function. Under normal circumstances, these gut bacteria are referred to as indigenous microbiota, performing their customary functions; however, in the presence of disturbances, detrimental or opportunistic bacteria emerge, known as pathobionts [2]. Imbalances within the gut microbiota have been associated with various diseases, including obesity, metabolic disorders, inflammatory bowel diseases, colorectal cancer, allergies, and autoimmune disorders [1]. Of particular concern is the impact of immunosuppressants and antibiotics administered after kidney transplant surgeries, as they disrupt the patients' gut microbiome, alter indigenous microbiota, and promote the proliferation of pathobionts, resulting in a condition known as dysbiosis. Dysbiosis, in turn, may facilitate the development of acute kidney injury (AKI) by modifying SCFA composition and generating elevated levels of toxins. Both AKI and pathobionts can contribute to the progression of atherosclerosis, cardiovascular diseases, inflammation, and chronic kidney disease (CKD). If left untreated, CKD can escalate to infections and even rejection of the newly transplanted kidney by the recipient's immune system [2]. Objective: This project aims to 1) examine the degree of change occurred in the abundance and diversity of the gut microbiome, before and after kidney transplantation, and 2) identify treatments that support the microbiome in returning to its healthy, stable state.
Project 5: Regional and Seasonal Variation of Cyanotoxins
(George Mason University, 2023-08) Aaravabhoomi, Hasika; Field, Daniel; Gibson, Adam; Schlueter, Matthew; Shah, Rohan; Baxter, Patrick
Background: Harmful Algal Blooms (HABs) and their toxins thrive in warm, nutrient-rich freshwater conditions, and can produce harmful cyanotoxins. Typically, these cyanotoxins take the form of hepatotoxins, dermatoxins, or neurotoxins. Exposure to cyanotoxins can occur in various fashions, including skin-to-water contact, inhalation of fumes, ingestion of contaminated water, and indirect ingestion through contaminated water sources or aquatic animals [1]. Exposure to microcystins, a common hepatotoxin found in cyanobacteria blooms, has been linked to fatal liver damage in both humans and dogs [3]. Additional evidence connects cyanotoxin BMAA to neurodegenerative diseases, such as ALS and Parkinson’s disease [5]. Minimal treatment options are widely available. Government bodies therefore focus their efforts on cyanobacterial toxicosis prevention, commonly issuing public safety alerts and advisory warnings around peak HAB exposure areas [3]. Objective: This research examines how HAB blooms and cyanobacteria outbreaks vary both regionally and seasonally across the United States from 2008-2018.
Project 6: Kidney Sales and Trafficking
(George Mason University, 2023-08) Lee, Crystal; Peng, Kenneth; Sajjad, Aryan; Yeum, Daniel; Wang, Zifu
Background: Over the past few decades, international health authorities and law enforcement agencies have taken substantial initiatives to counteract the illicit practice of organ trade. These endeavors reflect a collective commitment to address the pressing issue of organ trafficking, which preys on vulnerable individuals and undermines ethical medical practices. In the 1980s and onwards, the World Health Organization (WHO) has been instrumental in formulating guidelines for human organ transplantation, emphasizing the importance of voluntary donations, transparency, and ethical sourcing [1]. Notably, INTERPOL launched Operation Organs in 2016, targeting criminal networks engaged in organ trafficking and emphasizing cross-border cooperation [4]. Despite the concerted efforts to combat the illegal practice of organ trade, instances of such illicit activities persist. The illicit kidney trade remains a complex and multifaceted phenomenon involving various transnational actors, including sellers, buyers, brokers, and surgical facilities [5]. A notable characteristic of this trade is the intricate network that often facilitates the transactions. For instance, affluent buyers typically do not directly engage with financially disadvantaged sellers. Instead, kidneys procured from economically marginalized individuals are often passed through intermediaries, commonly referred to as brokers [5]. Subsequently, medical facilities responsible for the surgical procedures are identified, contacted, and engaged by these buyers. While the complex interrelationships among agents spanning various countries have been acknowledged, there has yet to be a quantitative methodology explored to systematically detect and analyze the structure of these transnational networks engaged in organ trade. Typically, these networks are presented and examined on a case-by-case basis through individual reports, news articles, and various media channels. Given the inherent difficulty in eradicating these illicit transactions and their intricate multi-agent nature, it becomes imperative to explore the underlying network dynamics and establish a robust spatiotemporal database to comprehensively study these operations. Objective: The study analyzed illegal kidney sales by generating a network of graphs using data of seller, buyer, and surgery countries and observed relationships among seller, buyer, and surgery countries.
Project 7: Viruses and Host Membranes
(George Mason University, 2023-08) Jacob, Riya; Kefale, Mikael; Khanna, Jahnavi; Kim, Andrew Jacob; McLaughlin, Madison; Li, Meng-Hao
Background: Rabies is a zoonotic disease caused by an unsegmented RNA virus of the Lyssavirus genus. It spreads between animals and humans through contact with mucosal membranes, abrasions, or the saliva of an infected animal, most commonly a dog. The rabies virus travels through the body's signal transmission pathways to reach the central nervous system and brain. Once it has entered the host, it attaches itself to nerve cells and begins to replicate. The virus then spreads throughout the body through neuronal pathways until it reaches the brain. The incubation period varies widely depending on the location of the bite and the severity of the infection. Once the virus reaches the brain, symptoms increase in severity, starting from flu-like symptoms to hydrophobia and delirium. The infected person enters the prodromal phase, during which they experience significant behavioral and physical changes, such as heightened aggression and pupil dilation. Progression to the "excited" or "furious" rabies phase leads to autonomic dysfunction and vicious, erratic behavior. The infected person may die in this phase or progress to the final stage, paralytic rabies, where they will eventually die. Objective: This project aims to develop a comprehensive understanding of mechanisms for infectivity (attachment and entry) by defining the landscape of rabies virus research through bibliometric analysis.

Browse

Recent Submissions