MSSRP projects – 2024

Preceptor:  Bon Trinh (2 students requested)
Department:  Pathology
Contact:  Phone (434) 982-2341, email:  bontrinh@virginia.edu
Project title:  See project description for more details.
Project description:  1. Protein-ncRNA coordination in myeloid cell development and AML
Failure in myeloid cell mat­u­ration is the cause of acute my­eloid leuke­mia (AML), a blood cancer with very poor patient outcome. We hypothesize that ncRNAs coordinate with pro­teins, in governing expression of im­portant myeloid genes via chromatin looping, and that aberrations in this molecular coordination contribute to AML progression (Fig. 2). To this end, we are 1) comprehensively characterizing protein-binding ncRNAs and demon­strate the effect of Protein-ncRNA coordination on chromatin architecture and epigenetic marks at myeloid gene loci, 2) determining ncRNA regula­tors of mye­loid gene expression, and 3) demon­strating that fusion proteins exhib­its their oncogenic functions through modulating ncRNAs. These studies will provide important mechanistic insights into protein- and ncRNA-medi­ated gene regulation in normal development and cancer progression. Related studies: Trinh et al, Blood J, 2021; Trinh and Tenen, US patent application, 2020; van der Kouwe et al., Blood 2021, Qiu et al, BioRxiv, https://doi.org/10.1101/2024.01.01.573782, under review; Korczmar et al, under revision.

2. Protein-ncRNA coordination in cancer drug response
Drug re­sistance is a ma­jor prob­lem in cancer treatment. To comprehen­sively investi­gate the role of ncRNA-pro­tein mediated gene regula­tion via chro­matin struc­ture in drug response, we are 1) leveraging bioinfor­mat­ic and biostatistical anal­yses of big data sets in identify­ing protein-ncRNA candi­dates that are respon­sive to popu­lar cancer drugs, 2) de­vel­op­ing genome wide CRISPR screens to identify ncRNA modula­tors of drug responses, and 3) de­termining ncRNA-medi­ated regulatory mecha­nisms in drug sensi­tiv­ity. The goals are to identify and estab­lish ncRNAs and proteins as diagnostic biomarkers and therapeutic targets (Fig. 3). Related studies: Trinh et al, Blood J, 2021; Trinh et al, Cancer Res, 2013;

Learn more: https://tinyurl.com/trinhlaboratory

Preceptor:  Melissa A. Little, MPH, PhD
Department:  PHS/Cancer Center
Contact:  Phone (434) 924-1935, email:  mal7uj@virginia.edu
Project title:  Community-based tobacco prevention and cessation interventions
Project description:  The Center for Tobacco Prevention and Control Research, led by Melissa A. Little, PhD, MPH, is looking for two MSSRP students to help with several community-based tobacco prevention and cessation interventions that are currently underway in the community. Current projects include:

QuitAid: An R01 funded through the National Cancer Institute to use a pragmatic approach, guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, to identify the essential components of an effective smoking cessation program that can easily integrate within community pharmacies in underserved rural areas (R01 CA267963, PI Little).

Built Environment: R01 through the National Institute on Drug Abuse to examine behavioral and environmental influences on tobacco initiation and re-initiation among Air Force Technical Trainees following a period of forced abstinence (R01 DA043468, PI Little).

Youth Brief Tobacco Intervention: A large grant funded through the Virginia Foundation for Healthy Youth to develop and test a school-based intervention to reduce tobacco and nicotine use among high school students in Virginia (8521389, PI Little).

QuitAid FQHC: A pilot grant from the Cancer Control and Population Health (CPH) program at the University of Virginia Cancer Center to determine the feasibility of a pharmacist-delivered medication therapy management (MTM) approach to smoking cessation within Federally Qualified Health Centers to reduce tobacco-related disparities among low-income smokers (PI Little).

MSSRP students will have the opportunity to assist on these projects in a variety of roles, including study start-up activities, data collection and manuscript preparation.

Preceptor:  Thomas Hartka, MD, MS, MSDS
Department:  Emergency Medicine
Contact: Phone:  (434) 924-8488, email:  trh6u@uvahealth.org
Project title:  Investigating Sex Disparities in Lower Extremity Injuries Resulting from Motor Vehicle Collisions
Project description:  Research indicates a disproportionate incidence of lower extremity fractures among female occupants involved in frontal collisions compared to their male counterparts. This project aims to conduct an in-depth examination by aggregating and scrutinizing data spanning multiple years sourced from the National Automotive Sampling System (NASS) and the Crash Injury Surveillance System (CISS). The primary objective is to discern the underlying factors contributing to these sex-based differentials through advanced statistical methodologies, including logistic regression and other analytical techniques.

Strong programming skills are necessary. Applicants must be experienced with Python or R.

Preceptor:  Daniel Zegarra-Ruiz, PhD
Department:  MIC/CIC
Contact:  Phone:  (203) 824-7028, email:  kfh4kn@virginia.edu
Project title:  Lupus-related pathobionts effects in the type I interferon signaling pathway
Project description:  We will investigate how pathobionts relevant to lupus pathogenesis can drive type I IFN responses in immune cells.  Our goal is to determine how pathobionts can stimulate type I IFN responses in immune cells, which are involved in lupus pathogenesis. To achieve this, we will conduct in vitro studies where we will co-culture commensals and pathobionts with plasmacytoid dendritic cells. By doing this, we hope to gain a better understanding of how microbes can influence the interferon pathways and contribute to the development of lupus.

Preceptor:  John F. Angle
Department:  Radiology
Contact: Phone:  (434) 924-1562, email:  jfa3h@virginia.edu
Project title:  Dose reduction in digital subtraction angiography:
Project description:  Image guided endovascular procedures require fluoroscopy but also the acquisition and interpretation of “pictures” of the vasculature called digital subtraction angiography, or DSA for short. Imaging vendors provide baseline imaging parameters that minimize patient and operator dose but provide high quality images. There is little research into what is the minimal acceptable exposure to minimize x-ray dose. The focus of this research is to test low dose DSA in a phantom and clinical practice. The student will help build phantoms, make test exposures, monitor procedures using low dose DSA, and lead blinded image interpretations by radiologists, and participate in analysis of the results.

Preceptor:  Xin Hu
Department:  Public Health Sciences
Contact: Phone: (404) 940-6720, email: xin.hu@virginia.edu
Project title: Palliative Care Laws and Utilization Among Advanced Stage Cancer Patients
Project description:  Early integration of specialty palliative care, often occurring at outpatient settings, is recommended by clinical guidelines for patients with advanced cancer, based on evidence for improved quality of life and survival. However, the utilization is low due to multi-faceted reasons, including providers’ factors such as a shortage of specialty-trained palliative care physicians, billing and documentation burden, payment structures, and patients’ factors such as misconception of palliative care, and time and financial burden. For this summer program, students can be involved in the following activities:

1. Review and summarize palliative care related laws and regulations, including laws that affect physician workforce, payment, quality, and etc.
2. Review EHR (after appropriate training) related to palliative care utilization to identify billing and documentation patterns, such as use of appropriate diagnosis codes and medical notes, and be involved in developing an AI algorithm to identify palliative care utilization from EHR.
3. Conduct literature review, help with IRB preparation, manuscript, and other report development for other ongoing activities related to palliative care.

Preceptor: Shengyi Iris Sun, Ph.D.
Department:  Pharmacology
Contact: Phone:  (434) 243-1271, email:  bjk5fz@virginia.edu
Project title:  Investigating ERAD in ANGPTL3 Biogenesis and Lipid Metabolism
Project description:  Endoplasmic reticulum-associated degradation (ERAD) is a quality-control process responsible for disposing of misfolded proteins in the ER. Our project focuses on exploring the role of ERAD in the biogenesis and intracellular trafficking of ANGPTL3, a key regulator of lipid homeostasis. ANGPTL3 plays a crucial role in controlling systemic lipid partitioning by regulating triglyceride clearance from circulation. Despite its significance in lipid metabolism and therapeutic potential in cardiovascular diseases, the mechanisms underlying its intracellular biogenesis in hepatocytes remain largely unexplored. By understanding the interplay between ERAD and ANGPTL3 maturation and secretion from the ER, we aim to uncover insights into lipid metabolism regulation and potential therapeutic interventions.

Preceptor:  Yuh-Hwa Wang, PhD
Department:  BMG
Contact: Phone:  (336) 782-7911, email:  yw4b@virginia.edu
Project title:  Non-smoking-related chemical exposures and genetic predisposition of DNA fragile sites in the formation of ALK, ROS1, and RET rearrangements in female non-smoker lung cancer patients
Project description:  ALK, ROS1, and RET genes are driver oncogenes, and rearrangements between one of these three genes and other genes are identified in approximately 10 % of non-small cell lung cancers (NSCLCs) in the United States. One interesting common feature among the ALK, ROS1, and RET fusions is that they are found most frequently in patients of younger age (< 60 years) and non-smokers. Non-smoker lung cancer is about three times more common in females than males. ALK, ROS1, and RET are located within known fragile sites, FRA2N, FRA6C, and FRA10C, respectively. Non-cytotoxic levels of various environmental and dietary chemicals such as benzene and diethylnitrosamine can significantly increase fragile site breakage. Furthermore, premenopausal women have higher NSCLC incidence compared to men, but not postmenopausal women, suggesting a critical role of estrogen in developing NSCLCs. Working Hypothesis: We hypothesize that external environmental and dietary chemicals in combination with estrogen, contribute to the increased incidence of ALK, ROS1, and RET fusions, through their effects on DNA breakage at rearrangement-participating gene regions. Specific Aims: AIM I. Determine whether treatment with dietary/environmental chemicals known to induce fragile sites can generate DNA breaks at ALK, ROS1, and RET, and can lead to their respective rearrangements in human lung cells. AIM II. Employ epidemiological and genomic data of NSCLC patients to prioritize other chemicals and identify genetic contributors for the formation of the ALK, ROS1, and RET fusions.

Preceptor:  Shrirang M Gadrey
Department:  Medicine
Contact: Phone:  (434) 825-0674, email:  smg7t@uvahealth.org
Project title:  Labored breathing
Project description:  Labored breathing is a red-flag sign that identifies unstable patients. But there is no device to test for labored breathing or to quantify its severity. Visual assessments are the standard of care – and they are exactly as unreliable as they sound. ARK is the first device that measures labored breathing physiology in a real-world setting. On the heels of successful validation in adults, this project looks to prove technical feasibility and clinical utility in the early detection and risk stratification in pediatric asthma. The MSSRP student will be expected to learn to screen, enroll, consent, and make ARK recordings in three groups of children : no asthma; chronic stable asthma; and acutely exacerbated asthma.

Preceptor:  Robert H. Thiele, M.D., M.B.A.
Department:  Anesthesiology
Contact: Phone:  (434) 243-9412, email:  rht7w@uvahealth.org
Project title:  surgical site infections (SSI) and central line associated bloodstream infections (CLABSI)
Project description:  Our laboratory is developing technology to address two important problems, surgical site infections (SSI) and central line associated bloodstream infections (CLABSI) using both blue-violet light and ultraviolet light. Antimicrobial light therapy is an innovative approach to controlling hospital associated infections. We collaborate with Dr. Chelsea Marie (Infectious Diseases) to perform in vitro and in vivo analysis of the antimicrobial properties light treatment on common hospital acquired pathogens. The primary role of the student will be to assist us in the execution of our ongoing animal trial, in which we are testing the ability of our technology to reduce SSI in a rat model of foreign body infection. This will include quantitative microbial culture, animal surgery (observe or perform), clinical scoring, histopathologic analysis, and comparative studies of bacterial growth and luminescence after light-mediated disinfection using in vivo and in vitro models. In addition to that work, the student will have the opportunity to learn microbiology skills from related work conducted Dr. Marie’s laboratory and there are opportunities for student-directed investigations into other aspects of light-mediated disinfection in the setting of hospital acquired infection. Potential experiments could include mechanisms of light-mediated killing of bacteria, efficacy for disinfection of C. difficile spores, trials of drain disinfection, probing effects of antimicrobial light on mammalian cells, analysis of surface disinfection properties, etc.

Preceptor:  Arjun Dirghangi, MD, MHS
Department:  Ophthalmology
Contact: Phone: (917) 723-1599, email:  ad3bb@uvahealth.org
Project title:  DISC-ViEW: Digital Imaging Screening and Classification – Video Enhanced Workflow
Project description:  Glaucoma is the leading cause of irreversible blindness worldwide, with over 8.4 million people bilaterally blind from glaucoma in 2010. Furthermore, the burden of severe disease and poor outcomes is not evenly distributed. Racial and ethnic minority individuals in the US with glaucoma face several challenges, including disparities in diagnostic testing, and delayed detection of glaucoma progression leading to a greater likelihood of progression to blindness. As such there is a critical need to develop low-cost screening systems to aid optometrists in early diagnosing glaucoma and improve clinical outcomes, especially in underserved communities. This project aims to develop a low-cost glaucoma detection system using an indirect ophthalmoscope and develop machine learning-based tools to automatically perform quality control, image segmentation, and estimation of glaucoma risk. We will demonstrate the feasibility of this system using real world data collected in underserved environments and address challenges such as image quality differences, device differences, and staff education.

Traditional methods of glaucoma management often fall short in predicting and preventing disease progression, particularly in high-risk groups. In fact, about half of glaucoma patients remain undiagnosed worldwide. This gap is more pronounced in underserved communities, where social determinants of health (SDOH) can influence disease outcomes. Additionally, the accuracy of glaucoma diagnosis is highly contingent on the quality of optic nerve imaging. Compounding the fact that large-scale community-based glaucoma screening is not currently performed in the United States, high-quality imaging equipment and trained personnel may not be present at the majority of outpatient eye clinics where the majority of patients receive care (and glaucoma screening). However, existing imaging methods often fail to capture the nuances necessary for glaucoma diagnosis in its early stages, when intervention is most beneficial. This limitation is even more pronounced in underserved and more resource-constrained community clinical settings.

Thus, despite modern advancements, approximately half of glaucoma cases remain undetected in developed nations, due in part to the limitations of current screening methods during routine eye examinations, which yield a published sensitivity of only 59% and specificity of 73% for glaucoma detection through dilated ophthalmoscopy. The Disc Damage Likelihood Scale (DDLS), with its greater sensitivity (74%) and specificity (88%), surpasses traditional methods and even advanced imaging techniques like OCT in detecting early glaucomatous damage. However, its practical implementation in clinical settings is limited due to its complexity.

The current research — DISC-ViEW: Digital Imaging Screening and Classification – Video Enhanced Workflow — aims to address this limitation by developing machine learning methods to segment optic nerve head features from video frames, thus automating the DDLS assessment (Formichella et al., 2020; Singh et al., 2022). This automation promises to make DDLS more accessible and consistent in its application, enhancing its utility in glaucoma screening, especially in community healthcare settings where access to advanced imaging technologies like OCT might be limited.

Objective: Organize, collect, and annotate a representative library of clinical fundus images and videos of optic nerve ophthalmoscopy including glaucoma patients to develop a training dataset for the DISC-ViEW project.

Activities: The student will be involved in:
Coordinating with departmental glaucoma fellow, Dr. Dirghangi, and Computer Science/School of Data Science subject matter experts. Coordination of research clinic sessions and collecting and organizing a diverse library of representative deidentified fundus images using a novel indirect ophthalmoscope-mounted wireless fundus imaging adapter. Selection, training, and deployment of image processing tools suitable for annotation of optic disc imagery in still photographs and video frames. Coordination with Prof. Miaomiao Zhang (UVA CS) and Prof. Don Brown (UVA SDS) regarding selection and testing of existing optic disc segmentation models on existing high-quality public image libraries, and clinical photographs from pilot patient images. Annotating images and video frames (with members of UVA glaucoma service) to identify key features of the optic disc, comparable to existing annotated databases used in glaucoma research. Coordination with CS colleagues to mock up a web application for manual DDLS scoring and annotation.
Training and Supervision: The student will be supervised directly by Dr. Dirghangi, as well as members of the UVA Glaucoma service and colleagues in UVA Department of Computer Science and School of Data Science, and will work closely with other team members to ensure accurate data collection and annotation. Training on ethical considerations and handling of PHI will be provided and emphasized.

Integration into MSSRP
Schedule: The project will span the MSSRP summer session, with specific milestones set for training, data collection, annotation, and review phases.

Expected Outcomes: By the end of the project, the student should have a comprehensive understanding of the clinical and technical aspects of image annotation in glaucoma research, and the ethical use of AI in Ophthalmology. The project will also aim to identify and deploy key tools for image labeling, and produce a pilot set of annotated clinical images and short video clips ready for testing of best-in-class existing disc segmentation machine learning algorithms to produce a baseline level of performance, as compared to performance in available high-quality labeled public fundus images. A final report will be produced which should reference the peer reviewed literature on this topic, and the candidate will be encouraged to present relevant findings in scientific meetings and leverage the report to draft a manuscript suitable for publication.

Preceptor:  Masahiro Morikawa, MD, MPH
Department:  Family Medicine
Contact:  Phone: (434) 924-6936, email:  mm7jc@virginia.edu
Project title:  Improving both patient satisfaction and efficiency together with functional examination table
Project description:  Patients are coming to see physicians for professional opinions. And our professional opinions are formulated on our history taking and physical examination. There are numerous evidences that physical examination is directly related to patient satisfaction. Physical examination is also a key element for efficiency of the visit as well.

This pilot project will try to demonstrate the differences between usual care and visits with fully electric exam table that will allow us to conduct thorough examination efficiently.
The student will help organize and conduct interview surveys for this pilot project.

Preceptor:  Caroline Tippett, DPM
Department:  Orthopedics
Contact: Phone (252) 289-7075, email:  qhq6sc@uvahealth.org
Project title: Retrospective chart review of reduction in major amputation after integration of podiatry into the health system.
Project description:  Maintaining database of limb preservation patients with future projects on improvements after implementation of limb preservation service.
Retrospective chart review of patient outcomes with and without 6 week course of IV antibiotics for foot osteomyelitis.

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