University Of Maryland Baltimore County

NIH Research Projects · FY 2026 · 2020-04

PROJECT SUMMARY/ABSTRACT The purpose of this application is to renew the University of Maryland Baltimore County's (UMBC) current Undergraduate Research Initiative for Student Enhancement (U-RISE) training grant, (T34GM136497, U-RISE at University of Maryland Baltimore County) and obtain funding for an additional five years to continue to support research training of 35 trainees per year. During the first 4 years of the current grant 108 students have been supported by the program with 93% of the 73-students graduating with a B.S in STEM and 60% matriculating directly into either a Ph.D. or M.D. / Ph.D. program, this is 4 times higher than a control group. The aim of U-RISE is to develop a diverse pool of undergraduates who complete their baccalaureate degree, and transition into and complete biomedical, research-focused higher degree programs (e.g., Ph.D. or M.D./Ph.D.) and pursue biomedical research careers. All qualified students with a strong commitment to diversity, equity and inclusion are welcome to apply. Because evidence suggests that participation in the field of biomedical research by historically underrepresented groups can help to alleviate existing health disparities, applicants with backgrounds and life experiences that are underrepresented in science, technology, engineering and mathematics (STEM) are encouraged to apply; specifically, racial and ethnic minorities, students of low socioeconomic status, and students with disabilities. The program will provide activities to assure: (i) excellence in academic science, (ii) understanding and adapting to the intensity and rigor of contemporary scientific research, (iii) student interest in pursuing a Ph.D. or M.D/Ph.D. degree and a career as a researcher in the biomedical, behavioral, and mathematical sciences, as well as (iv) selection of graduate school, and developing successful admission applications, and (v) an emphasis on student mental health and wellness. U-RISE at UMBC will provide comprehensive financial support to ensure that trainees can focus on preparing for a smooth and successful transition from UMBC to competitive graduate programs at highly ranked institutions. Students with relevant majors will be recruited from UMBC and community colleges during the first semester of their sophomore year, and successful applicants will be appointed to U-RISE in April. Admission eligibility will require a 3.2 cumulative GPA, a minimum of 60 college-credits, and commitment to a research career. Trainee participation will begin with a summer research internship and continue in the junior and senior academic years with academically challenging courses, plus 8-10 hours per week in sustained research with a faculty mentor at UMBC or a nearby institution. The 2–3-year program also consists of required development courses (i.e., professional development, scientific writing, rigor and reproducibility, research ethics and policy) designed specifically for U-RISE participants. Program design and participant selection will be guided by the U-RISE Advisory Committee and administered by the U-RISE Program Director) with the assistance of the full-time U- RISE Associate Director.

NIH Research Projects · FY 2026 · 2019-08

Project Summary This research program focuses on two inadequately understood metalloprotein systems that are linked to health and human disease and aims to uncover the mechanistic underpinnings of these essential biological processes. The first biological process of focus is bacterial ferrous iron (Fe2+) generation, acquisition, and sensing. The chief prokaryotic Fe2+ acquisition system is the Feo system, which is present in nearly all bacteria and is used by pathogens to establish infection in mammalian hosts. Our previous work has begun to unravel the mechanistic details of this important iron acquisition pathway. Importantly, there is an emerging connection between Feo and additional membrane-bound proteins that function more broadly in bacterial Fe2+ homeostasis through the sensing Fe2+ to control biofilm formation (BqsR/S) and the utilization of Fe3+-siderophores to supply Fe2+ to the Feo system (membrane ferric reductases or mFRs). This proposal outlines a comprehensive approach to study these three systems (Feo, Bqs, mFRs) both in vitro and in vivo. Leveraging structural, spectroscopic, and biochemical analyses, this proposal aims to define the mechanism of bacterial Fe2+ generation, acquisition, and sensing, which will position future researchers to explore the urgent but broadly impactful possibility that these systems may be exploited to combat bacterial virulence. The second biological process of focus is eukaryotic post-translational arginylation, catalyzed by the enzyme arginyltransferase 1 (ATE1). ATE1-catalyzed arginylation typically targets the N-terminus of proteins, altering protein function and fate in vivo. Normal ATE1 activity is critical for neurogenesis, cardiovascular development, cancer, and viral infections, but the structural and mechanistic details of ATE1-mediated arginylation are sorely lacking, prohibiting the targeting of this system for therapeutic intervention. Our previous work has uncovered the structure of yeast ATE1 for the first time, has shown that ATE1s are O2-sensitive [Fe-S] proteins, and has developed a mechanistic framework for post-translational arginylation. This proposal aims to uncover the structure of the arginylation complex and its link to O2 sensitivity, to determine the structure of a mammalian ATE1, and to understand the evolution of ATE1. To achieve this goal, this proposal combines in vitro and in vivo structural, biochemical, and functional methods to elucidate the components of post-translation arginylation in order to design small molecules that target ATE1 for intervention. Combined, the results from this proposal hold the promise to aid in the development of therapeutics to abrogate bacterial virulence linked to iron homeostasis and to treat cellular diseases linked to post-translational arginylation.

NIH Research Projects · FY 2025 · 2017-05

Abstract Light has a profound effect on human physiology and behavior. In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) play a key role in light-dependent behaviors, including circadian photoentrainment, pupillary light reflex, sleep, mood, memory and learning. Originally thought to be a homogeneous population, ipRGCs are now known to be a diverse collection of cells with six subtypes (M1-6) in mouse. These subtypes differ in many ways, including expression levels of the photopigment melanopsin, dendritic stratification, synaptic inputs, firing patterns, and central projection targets in the brain. These ipRGCs respond to light by integrating intrinsic melanopsin-based phototransduction and extrinsic synaptic inputs driven by conventional rod and cone outer retinal photoreceptors. Early studies suggested that melanopsin phototransduction utilizes exclusively a Gq-signaling cascade that leads to the activation of Plc4 and TrpC-family ion channels. This model has been challenged, however, by discovery of alternative signaling pathways in non-M1 ipRGCs, but the precise identity of the signaling components remains controversial. These findings have thereby revealed a large gap in knowledge about the identity of the downstream components of melanopsin’s phototransduction cascade. Furthermore, we have recently shown that melanopsin signaling can be regulated by dopamine, a well-known neuromodulator in the retina, in a cell culture system. Our overall goal for this proposal is to understand how the complexity of the melanopsin-based signaling pathway and its regulation in distinct ipRGC subtypes contributes to the large array of behaviors. In Specific Aim 1, we will determine the physiological and behavioral consequences of dopamine-dependent melanopsin phosphorylation in M1 ipRGCs, using a knock-in mouse model, in which phosphorylation sites in melanopsin are mutated. In Specific Aim 2, we will identify distinct roles of M1 and M4 ipRGCs in light-dependent behaviors by subtype-selective manipulation of phototransduction pathways. These studies will provide a critical understanding of the biochemical and molecular mechanisms by which light influences human health and performance through the regulation of circadian rhythms, sleep, mood, memory and learning.

NIH Research Projects · FY 2026 · 1989-07

7. Project Summary/Abstract The overall goal of this project is to understand how the HIV-1 5′-leader RNA differentially directs diverse functions during viral replication, including intracellular trafficking, initiation of translation, recruitment of viral structural proteins (called Gag), and nucleation of virus assembly. Proposed studies build on our recent discovery that HIV-1 RNAs are transcribed with one, two or three 5ʹ-guanosines via alternate (heterogeneous) transcriptional start site usage – a new paradigm in HIV-1 RNA biology. Our studies revealed that 5′-capped transcripts that begin with a single guanosine (Cap1G) adopt a structure that sequesters the 5′-cap, promotes dimerization, and exposes Gag binding sites, thereby promoting their functions as genomes (gRNA). In contrast, 5′-capped transcripts that begin with two or three guanosines (Cap2G/Cap3G) adopt monomeric structures with an exposed 5′-cap that function in splicing and translation (mRNAs). The central hypothesis guiding our proposed studies is that cap sequestration enables the HIV-1 gRNA to avoid capture by the cellular RNA processing and translation machinery, and that a small number of Gag proteins (~2 dozen) are cooperatively recruited to assembly sites on a well-defined packaging signal (ΨCES) located within the gRNA 5′- leader. We now aim to identify molecular determinants of alternate transcription initiation and exploit this knowledge to differentially examine HIV-1 mRNA and gRNA trafficking and interactions in cells, probe RNA structural changes that occur during virus assembly and maturation, and identify key interactions that promote Gag:RNA assembly and might be exploited for drug targeting. Preliminary NMR and EM findings suggest that it should now be possible to determine the 3D structure of the Gag:RNA complex that nucleates HIV-1 virus particle assembly. NMR studies of large RNAs and protein-RNA complexes are technically challenging – the average size of NMR-derived RNA structures in the RNA Structure Database is only 30 nucleotides. But the potential payoff of the proposed studies is substantial and could ultimately lead not only to a more detailed understanding of how HIV-1 replicates, but also to the development of new approaches for the treatment of AIDS and to the engineering of gene delivery vectors with improved packaging efficiencies.