Unmatched MSSRP projects – 2023

Preceptor:  Bon Trinh
Department:  Pathology/UVACCC
Contact:  Phone: (434) 982-2341, email:  bontrinh@virginia.edu
Project title:  Project details listed below
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

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
More details about our research program can be found at https://tinyurl.com/trinhlaboratory

Preceptor:  Jaime Mata MS PhD
Department:  Radiology
Contact:  Phone:  (434) 243-6498, email:  jfm4q@virginia.edu
Project title: Focused Ultrasound delivery of miR-142-3p to boost the immune response in glioblastoma (GBM)
Project description:  Student will do research with MRI guided Focused Ultrasound (FUS) to treat gliobastoma (main project), and with Hyperpolarized Xe-129 Gas MRI (a newly FDA approved drug/technique) to detect and characterize lung disease.  The FUS-GBM data can potentially uncover a new potent clinically translatable experimental GBM therapy that uses FUS microRNA delivery to boost the GBM anti-tumor immune response and sensitize tumors to chemotherapy.  At the end of the seven weeks, the student should had written and submitted at least one manuscript as co-author.

Preceptor:  Bijoy Kundu, PhD
Department:  Radiology
Contact:  Phone:  (804) 397-9727, email:  bkk5a@virginia.edu
Project title:  Interictal dynamic FDG-PET in focal epilepsy
Project description:  Medically intractable epilepsy is a devastating disease. Some patients qualify for epilepsy surgery. Epilepsy surgery is curative in about two- thirds of those who undergo surgery, but to be a surgery candidate, a seizure focus – a “bad spot” in the brain – must be located. This proposal is a phase-2a case-control biomarker validation study of a novel method of brain imaging to be used in the non-invasive stage of evaluation of epilepsy surgery that offers an improved ability to locate the seizure focus. Our pilot studies with dynamic FDG PET imaging have shown improved sensitivity over standard methods of neuroimaging. One of the key tasks for the selected candidate will be to redesign and populate a research database for the above neuroimaging project in epilepsy, going back to primary patient records and adding new neuroimaging interpretations. This will be in addition to learning and contributing to visual, qualitative and quantitative image interpretation for standard of care neuroimaging and comparing to the novel dynamic PET.

The student will be working in the laboratories of Drs Bijoy Kundu in Radiology and Medical Imaging and Mark Quigg in the Department of Neurology. The student will also get an opportunity to work with grad and undergraduate students and residents and fellows in the computing and clinical labs of Drs. Kundu and Quigg.

Preceptor:  Muge Kuyumcu-Martinez
Department:  Molecular Physiology
Contact:  Phone:  (832) 723-4309, email:  pnc3uj@virginia.edu
Project title:
Project description:  The role of RNA binding proteins in adult and congenital heart diseases.

Preceptor:  Coleen McNamara
Department: CIC
Contact:  Phone: (434) 243-5854, email:  cam8c@virginia.edu
Project title:  Glucose 6 phosphate dehydrogenase deficiency (G6PD-d) in a murine model
Project description:  Glucose 6 phosphate dehydrogenase deficiency (G6PD-d) affects nearly a ½ billion people worldwide as the most common enzymopathy. Historically, researchers have focused on the impact of G6PD-d on red blood cells. However, recently there has been increasing recognition of the role of G6PD-d as a genetic and metabolomic modifier of multiple pathologies. One such pathology is cardiovascular disease (CVD), which is thought to be the result of chronic vascular inflammation.

Recent epidemiological studies of >25K patients have demonstrated a significantly increased risk of CVD in subjects with G6PD-d. Yet, no studies have been published that address if this relationship is causal nor has a mechanism been reported. Interestingly, immune cells play an important role in both preventing and exacerbating the CVD, and alterations in cellular metabolism such as those observed in G6PD-d play an important role in steering the function and inflammatory state of immune cells. One such cell type, the B-1b subset of B cells, have been shown to produce anti-oxidation-specific-epitope IgM that protects against atherosclerosis.

For this project, we aim to use a murine model of G6PD to characterize alterations in 1.) B-1b cell number through analysis of tissue specific flow cytometry, 2.) B-1b cell function through analysis of RNAseq data, and 3.) B-1b cell metabolism via analysis of metabolomics data generated by our collaborator Angelo D’Alessandro at the University of Colorado. Additionally, we aim to 4.) identify correlations between specific alterations in B-1b cell number, function, or metabolism with the degree of atherosclerosis in our murine model.

MSSRP student would be responsible for analyzing atherosclerosis in the humanized mice with both the Mediterranean and African G6PD variants. As time and interest allows, they can also participate in RNAseq and metabolomics data analysis alongside M4 research-year student, with assistance from experienced lab mentors.

Background Papers:

· Rosenfeld et al, Circ Res., 2015

· Upadhye et al, Circ Res., 2019

· Arai et al, J Atheroscler Thromb., 2021

Preceptor:  Michael S. Ryan, MD, MEHP
Department:  Pediatrics/CEE
Contact:  Phone:  (434) 987-7050, email:  michael.ryan@virginia.edu
Project title:  Conduct literature reviews, help draft IRB proposals, recruit participants for study, analyze data, and draft abstracts and/or manuscripts for publication.
Project description:  Medical education is in the process of transformation. Historically, trainees advanced through medical school on the basis of “time-in-seat” rather than demonstration of competence. The future of medical education involves recognition that advancement should take place if/when trainees develop the knowledge, skills, and attitudes required to practice medicine in a competent fashion. The Center for Excellence in Education at the UVA school of medicine is involved in several medical education research projects that revolve around the concept of competency-based medical education (CBME). The MSSRP student will participate in project(s) within this topic area in several capacities. They will have the opportunity to conduct literature reviews, help draft IRB proposals, recruit participants for study, analyze data, and draft abstracts and/or manuscripts for publication. Mentorship will be provided by educational research experts associated with the center who will promote the student’s acquisition of specific methodology used in medical education research.

Preceptor:  Jennifer M. Lobo, PhD
Department:  Public Health Sci.
Contact:  Phone:  (434) 924-2813,  email:  jem4yb@virginia.edu
Project title:  Deep learning of awake and sleep electrocardiography to identify atrial fibrillation risk in sleep apnea
Project description:  Project description: Atrial fibrillation (AF) is the most common cardiac arrhythmia, projected to affect 6-12 million people in the United States by the year 2050, and is responsible for significant morbidity and mortality. OSA may contribute to the development of AF through the heightened sympathetic activity and direct mechanical stretch of the atria that occur during obstructive apneic events. Through part of a larger study, we will use UVA data to build a prediction model for new onset AF in patients with OSA in clinical practice. Student responsibilities will include uploading raw sleep PSG data from CD archive to server at the Sleep Lab at UVA and extracting 12-lead ECG data from the Philips Vue program. A related student-led project that can be completed over the summer using available PSG and clinical data will be identified based on student interests.