Department of Biomedical Sciences Abstracts

Presenter(s): Kathleen McCarthy

Showcase Advisor: Nicholas Mantis

Abstract: Development of Lyme Disease vaccines are challenging because of the high antigenic variability associated with the disease-causing agent, Borrelia burgdorferi. Here, we investigated the C10 epitope as a possible vaccine and therapeutic target. The C10 epitope of Outer surface protein C (OspC) is conserved across >80% of OspC variants and represents one of the most immunodominant linear epitopes in patients. We characterized 6  high-affinity C10-targeting monoclonal antibodies (mAbs) for their ability to access and confer protection against infection. C10 mAbs bound OspC on live spirochetes and mediated bacterial agglutination and motility inhibition in vitro. Passive immunization with C10-11 provided dose-dependent protection in needle-challenge models but not in tick transmission. Route-dependent outcomes suggest C10 antibodies interfere with key process required by the bacteria in the skin, but not in the tick. Our findings suggest a C10 vaccine may limit skin infection even if it does not fully block tick transmission.

Presenter(s): Nicholas Keegan

Showcase Advisor: Joseph Wade

Abstract: Quorum sensing is a bacterial behavior that regulates gene expression in a population-dependent manner. LuxR-family quorum sensing is found in Gram-Negative bacteria and uses cytosolic transcription factors that interact with diffusible small molecule autoinducers called homoserine lactones (HSL). SmaR from Serratia ATCC 39006 is one of several LuxR-family proteins originally shown to only bind DNA when not bound by their autoinducers. Chromatin Immunoprecipitation Sequencing (ChIP-seq) data, however, indicate SmaR binds two different classes of DNA site: one in an expected autoinducer-sensitive manner and one in an unexpected autoinducer-insensitive manner. The goal of this project is to determine the role and mechanism of the two modes of SmaR binding. To this end we used both in vivo and in vitro binding and expression assays to characterize the direct regulon of SmaR. We observe that all expression associated with SmaR binding is controlled through the presence or absence of autoinducer.

Presenter(s): Sean Jones

Showcase Advisor: Pallavi Ghosh

Abstract: The mycobacterial cell wall plays a major role in bacterial physiology, including protection against hostile environments and chemicals such as antibiotics. The cell envelope consists of an inner leaflet of mycolic acids bound to arabinogalactan and an outer leaflet composed of free, unbound glycolipids. As environmental stressors are constantly changing, expression of genes involved in synthesizing and maintaining cell wall components needs to change too. One of the ways mycobacteria can respond to such stimuli is through extracyctoplasmic function (ECF) sigma factors. One of these ECF sigma factors in M. abscessus is SigD. In our current work, we characterize the regulon of SigD and show that it regulates different cell wall related and secreted proteins, becoming activated through cell wall perturbation. This work reveals that under normal conditions, SigD helps to decrease sensitivity to hydrophobic antibiotics and lower cell permeability by maintaining the cell wall through its regulon.

Presenter(s): Hannah Theriault

Showcase Advisor: Alexander Ciota

Abstract: Powassan virus (POWV) is a tick-borne flavivirus that causes encephalitic disease and is an emerging public health threat. Human cases have increased within the Northeast and Upper Midwestern United States. POWV is divided into lineages I and II (Deer tick virus [DTV]). DTV is vectored by Ixodes scapularis. POWV is maintained in strict transmission foci; because of this, transmissibility may be influenced by the specific pairing of tick and virus genotype. We hypothesize that POWV in the Northeast and Midwest are subject to distinct selective and stochastic pressures, driving genetic diversification and phenotypic variability. DTV isolates from New York and Minnesota had significant differences in in vitro replicative fitness. Results in field-derived I. scapularis suggest differences in viral replication and infection are influenced by population and viral strain. Specifically, DTV isolated from NYS was more infectious and grew to 8-fold higher titers in NYS I. scapularis than MN I. scapularis.

Presenter(s): Sethri Asamoah-Nani

Showcase Advisor: Bum Kyu-Lee

Abstract: The placenta is an organ that supports the life of a fetus during pregnancy. Understanding key regulators in placental cells helps improve comprehension of placental functions and their influence on cell phenotypes.  

RNA-sequencing analysis shows that LCTM1 and LCTM1-AS2 are highly expressed in Syncytiotrophoblasts (STB)- a placental cell layer. In this study, we aim to clone genes into an overexpression vector to investigate their roles in human placenta development. To do this, LCTM1 and LCTM1-AS2 are amplified using primers with STB cDNA as the template and cloned into the overexpression plasmid vector. In later experiments, cloned genes will be overexpressed in other placenta cell types to determine whether increased expression can cause other cells to develop phenotypic characteristics like STB cells.   

A better understanding of molecular processes that regulate placental cell function contributes to improved knowledge and advances research into medical conditions that affect the placenta and fetal development.

Presenter(s): Rhiannon Mariano

Showcase Advisor: Sian Owen

Abstract: Carbapenem-resistant bacteria pose a major global health threat, largely driven by the horizontal spread of carbapenemase-encoding plasmids. These plasmids disseminate through bacterial populations via conjugation, a process mediated by conjugative pili that also serve as receptors for plasmid-dependent bacteriophages targeting plasmid-carrying bacteria. This project aims to exploit this vulnerability by engineering or evolving hyper-conjugative plasmid variants with enhanced pilus expression to facilitate the isolation of novel plasmid-dependent phages from environmental samples. In parallel, well-characterized model conjugative plasmids will be used to visualize pilus expression and monitor phage–pili interactions using fluorescence-based labeling approaches. By identifying genetic and regulatory factors controlling pilus expression and plasmid transfer, this work will provide key insights into conjugative plasmid biology and phage–host interactions. Ultimately, these studies will establish a platform for developing phage-based precision antimicrobials designed to eliminate plasmid-mediated carbapenem resistance.

Presenter(s): Kass Sjostrom

Showcase Advisor: Todd Gray

Abstract: The type VII secretion systems (T7SS) function as adaptive toolsets that mycobacteria use for interactions.  In Mycobacterium smegmatis, T7SS factors are required for a horizontal gene transfer process called distributive conjugal transfer (DCT). DCT assays are a tractable, experimental, system to dissect cell-contact dependent DNA exchange. Here we show a conserved transcriptional repressor, known as EspM, is pivotal in transmitting the signal that ultimately induces key T7SS in the conjugative recipient cell. We hypothesize that EspM’s repression is rapidly released upon contact with partner cell as detected by a mating identity complex identified in our lab. We will identify the mechanism of this interaction through DCT, molecular genetics, fluorescent microscopy, co-immunoprecipitations, and targeted protein mutations. Characterizing EspM’s regulation mechanism will elucidate contact specific T7SS responses. Mycobacteria have repurposed these T7SS responses to community responses for pathogenicity. Regulatory proteins in the ESX-1 signaling system are high-value targets for potential novel therapeutics.

Presenter(s): Pattanai Konpetch

Showcase Advisor: Haixin Sui

Abstract: Primary cilia are essential signaling hubs that rely on the Intraflagellar Transport (IFT) trains to move cargos along axonemal microtubule complex (MtC) tracks for cilia maintenance and signaling molecule delivery. While current models from motile cilia suggest that IFT trains use different subtubules to avoid collisions, our recent study—using correlations from light microscopy and serial section electron tomography of resin-embedded samples—indicates that, in primary cilia, IFT does not prefer specific tracks and can travel along multiple MtCs. To verify these findings, we used cryo-electron tomography (cryo-ET) to examine in situ IFT-MtC interactions in vitreously frozen cilia that best preserve their native structure. Our results show that, under close-to-native conditions, IFT trains can interact with several MtCs simultaneously. This research confirms a unique transport model for primary cilia, enhancing our understanding of the structural mechanisms behind cargo transport and cell signaling.

Presenter(s): Gillian Belarmino

Showcase Advisor: Haixin Sui

Abstract: ATP-binding mcr11-regulator (AbmR) from Mycobacterium tuberculosis (Mtb) functions as a transcription factor that upregulates the expression of Mcr11, a stress-responsive small RNA. Additionally, purified AbmR assembles into 39S complexes that contain RNA. Our structural studies revealed a DNA-binding ribbon-helix-helix (RHH) motif formed by dimeric AbmR. However, in the 39S complex, the RHH motif faces inward, preventing interaction with DNA. To examine AbmR’s role as a transcription factor, we developed a maltose-binding protein (MBP)-AbmR fusion protein that blocks 39S complex formation, exposing the RHH motif of the AbmR dimer. This approach enabled us to analyze the influence of ATP and pH on DNA and AbmR interactions through electrophoretic mobility shift assays (EMSA). These results were complemented with mass photometry data of wtAbmR at different pH levels and provided insight into the functional mechanisms of AbmR.

Presenter(s): Elizabeth Kincaid

Showcase Advisor: Mathew Kohn

Abstract: In New York State (NYS), diagnoses of emerging vector-borne arboviral infections are increasing in number. One such infection is Powassan encephalitis (POW), a rare but serious tick-borne disease that can result in encephalitis and death. We studied retrospective reported Powassan virus infection cases spanning 2013 to 2023 in NYS. Using deidentified patient data from electronic case surveillance records, we explored Powassan virus infection cases that were classified as probable or confirmed. We also explored the role of vector-borne disease coinfections on Powassan virus disease progression and outcomes, as Ixodes scapularis, the main vector species for POW, is indicated as the primary tick vector of several other pathogens in NYS. This study hopes to highlight a growing need for targeted public health messaging and interventions to reduce tick bite risk.

Presenter(s): Biqing Liang

Showcase Advisor: Jon Paczkowski

Abstract: Pseudomonas aeruginosa are gram-negative opportunistic bacteria causing hospital acquired infections, affecting especially blood, lung, and urinary tract. In Pseudomonas aeruginosa, the quorum sensing pathway modulates the bacterial population through the production of signaling molecules. The loss of function mutations of LasR, a quorum sensing master regulator modulating the production of multiple virulence factors, are vastly reported in clinical isolates from cystic fibrosis patients. Previous studies had shown the altered phenotypes in the lasR- population compared to the wild type counterparts, however, how the phenotypes and genetic makeups in wild type and lasR- culture change under the stress from dispersal and reattachment during infection is yet unknown. Here, through lab evolution, we mimicked the loop of dispersal and aggregation in planktonic state bacteria during the progression of infection in wild type and ΔlasR PA strains and performed phenotypic and genetic characterizations, to reveal a divergence in their adaptation mechanism.

Presenter(s): Rachel Lange

Showcase Advisor: Alexander Ciota

Abstract: Powassan virus (POWV, Flaviviridae) is a tick-borne virus endemic to North America first recognized in 1958. Ticks were incriminated as primary vectors, but it wasn’t until the incursion of I. scapularis northward that human cases increased. To date over 5 tick species have been shown to support POWV, but the role of a vertebrate reservoir remains undefined. Early investigations suggested mustelids (i.e. groundhogs or skunks) and small rodents (i.e. squirrels) were potential reservoirs while recent work has implicated shrews. Our study aimed to further explore vertebrate involvement in POWV circulation through targeted wildlife screens and field collections of mustelids and small forest fauna from New York State. These studies revealed high rates of POWV in two shrew species and evidence of infection in multiple mink and fishers. Together, these data highlight hosts beyond the accepted paradigm that may contribute to POWV ecological maintenance and transmission.

Presenter(s): Tara Chakravarthi

Showcase Advisor: Joe Wade

Abstract: The regulation of transcription in bacteria is essential for maintaining proper gene expression and cell growth. Regulatory elements and proteins control transcription to ensure accurate gene and protein expression. A known regulatory sequence in E. coli is the “boxA” motif, a conserved nucleotide sequence associated with ribosomal RNA, CRISPR arrays, and genes encoding proteins involved in transcription. A group of proteins, the Nus factors, form a complex and bind to the BoxA motif, regulating transcription by preventing Rho-mediated termination, chaperoning rRNA folding, or stabilizing RNA polymerase as it transcribes. Several sites in the E. coli genome harbor sequences that resemble the boxA conserved motif, but whether they function as true BoxA sites and recruit the Nus complex remains unknown. The goal of this project is to identify novel boxA sites, identify other sequence elements that could recruit the Nus complex, and determine the role of boxA motifs in transcriptional regulation.

Presenter(s): Laura Munn

Showcase Advisor: Alexander Ciota

Abstract: Transmission potential of vector-borne pathogens is altered by environmental variables. Statistical models indicate significant effects of both temperature and humidity on the transmission of mosquito-borne viruses, including West Nile virus (WNV), yet empirical studies have focused almost exclusively on temperature. This gap limits the accuracy of predictive models that can guide vector control strategies. To address this, we experimentally examined how temperature and humidity interact to influence mosquito fitness and transmission potential. Using Culex pipiens, a primary vector of WNV, we evaluated mosquito development, survival, feeding rates, fecundity, and vector competence under combinations of temperature (20°C, 25°C, 30°C) and relative humidity (50%, 70%, 90%). Our findings demonstrate that humidity significantly enhances adult survival, blood-feeding rates, and increases infection and dissemination rates of WNV at higher temperatures. These results highlight the complex interactions among environmental variables that shape vectorial capacity and emphasize the need to integrate humidity into climate-informed predictive models.

Presenter(s): Mohamed Salamah

Showcase Advisor: Bum Kyu-Lee

Abstract: The placenta is essential for fetal survival, mediating nutrient and gas exchange, hormonal regulation, and immunological protection. Its main functional cells are trophoblasts, including cytotrophoblasts syncytiotrophoblasts , and extravillous trophoblasts. CTs act as precursor cells that differentiate into STs and EVTs to build and maintain placental structure and function. Disrupted trophoblast differentiation is linked to pregnancy complications such as preeclampsia, fetal growth restriction, and miscarriage. However, the molecular mechanisms controlling trophoblast lineage decisions remain unclear. GTF2I, a transcription factor important in embryonic development, causes midgestational death in knockout mice due to vascular and neural defects, yet its role in placental development is largely unexplored. Our preliminary data show that GTF2I expression decreases during trophoblast differentiation, while its antisense long non-coding RNA, GTF2I-AS1, increases. This reciprocal pattern suggests a regulatory mechanism balancing trophoblast stem cell maintenance and differentiation. We hypothesize that GTF2I supports TSC stemness, while GTF2I-AS1 suppresses GTF2I to promote differentiation.

Presenter(s): Ayesha Tahir

Showcase Advisor: Douglas Conklin

Abstract: ABL2  was identified as the top survival factor among 83 tyrosine kinases in breast cancer cells in our lab. Two isoforms of ABL2 with alternative N termini are produced using distinct TSS. Both isoforms are phylogenetically conserved in mammals;  ABL2.m is myristoylated, whereas ABL2.p contains predicted palmitoylation sites at Cys-22 and Cys-23. Cys-23 is highly conserved in mammals except rats and mice, likely reflecting later clade evolution. Exon 1 of ABL2.p also contains a conserved Tyr-13 predicted to be phosphorylated by PDGFRB, suggesting interplay between palmitoylation and phosphorylation. Computational analyses show ABL2.m predominates in normal tissues, while ABL2.p is elevated in solid tumors and leukemias and correlates with poorer survival in breast cancer. Transcription factor analysis suggests ABL2.m is regulated by lineage and cell-cycle factors, whereas ABL2.p responds to stress and inflammatory signaling. Ongoing studies aim to investigate differential biology and expression of ABL2 isoforms in tumors.

Presenter(s): Nathalie Colon-Torres

Showcase Advisor: Jon Paczkowski

Abstract: Rhamnolipids produced by Pseudomonas aeruginosa are an important virulence factor that aids in mobility across surfaces. They are produced by the RhlA enzyme, encoded in the rhlA gene that is regulated by RhlR of the quorum sensing circuit, along with its cofactor PqsE. Fis is a nucleoid associated protein that binds DNA, with a role in gene expression. We showed that Fis negatively regulates expression of rhlA. Here, we use DNA footprinting (Footprint-Seq) to determine the protection region by Fis and the RhlR-PqsE complex at the rhlA promoter. This assay revealed that Fis and RhlR-PqsE occupancy is unique within the promoter architecture on rhlA. Additionally, we probe the effect of Fis repression on regulation of rhlA by assessing swarming and rhamnolipid production utilizing CRISPRi. Subsequent work utilizing Footprint-Seq and binding assays aim to determine the mechanism of Fis repression of RhlR-dependent transcription on rhlA and regulation on other QS promoters.

Presenter(s): Yingchao Fan

Showcase Advisor: Joseph Wade

Abstract: CRISPR–Cas systems provide adaptive immunity in prokaryotes by acquiring short DNA fragments (prespacers) from invading genetic elements and integrating them into CRISPR arrays as spacers. CRISPR arrays are transcribed and processed into CRISPR RNAs (crRNAs), which guide surveillance complexes to bind complementary protospacer sequences in foreign DNA. In the Escherichia coli type I-E CRISPR-Cas system, primed adaptation is a process that enables highly efficient spacer acquisition from foreign DNA that is targeted for degradation. Here, we provide evidence that primed adaptation proceeds through two parallel mechanisms that involve translocation of the Cas3 nuclease in opposite directions from the DNA-bound surveillance complex. Our data suggests distinct early events prior to Cas3 translocation. Future work will investigate the role of the Cas1–Cas2 complex in strand-specific translocation during primed adaptation.

Presenter(s): Jacqueline Chouinard

Showcase Advisor: Kathleen McDonough

Abstract: Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), continues to be a global health threat as it is the world’s leading infectious disease killer.  It typically affects the lungs when the bacterium is taken up by alveolar macrophages and evades host defenses.  The DosR regulon is a collection of genes that contribute to dormancy of Mtb to ensure survival for long periods of time within its host, leading to latent TB infection.  Within the host, Mtb encounters hypoxic conditions during infection, however previous studies have not determined whether macrophages in hypoxia are better at phagocytosis of Mtb and if the induction of the DosR regulon affects this.  By infecting macrophages in normoxia and hypoxia, we found that hypoxia enhances phagocytosis of Mtb into macrophages but the induction of the DosR regulon has no impact. Further experiments will investigate how hypoxia impacts induction of the DosR regulon within macrophages.

Presenter(s): Lia Prager

Showcase Advisor: Jon Paczkowski

Abstract: Pseudomonas aeruginosa is an opportunistic pathogen that utilizes quorum sensing (QS) to regulate virulence and biofilm formation. QS is a cell-cell bacterial communication mechanism that uses signaling molecules called autoinducers (AI) to drive group behaviors like virulence factor production and pathogenesis. QS-mediated pathogenesis is dependent on the transcriptional activator RhlR, which is controlled by the AI N-butyryl-L-homoserine lactone (C4HSL) and the metallo-β-hydrolase PqsE. Studies showed that PqsE enhances the DNA binding affinity of RhlR. Each effector, exerts its influence at overlapping and distinct promoters to alter the transcriptional output of target genes in the RhlR regulon. Previous research showed that RhlR binds specific promoters independently of C4HSL but is still highly dependent on PqsE for the activation of those genes. We plan to ascertain the promoter elements that dictate the temporal regulation of RhlR-mediated gene expression across the QS regulon, with focus on the contributions of PqsE and C4HSL dependencies.

Presenter(s): Caleb Mallery

Showcase Advisor: Jon Paczkowski

Abstract: Quorum sensing (QS) enables bacteria to coordinate collective behaviors in response to population density, yet, mechanisms that reset QS circuits remain poorly understood. In Pseudomonas aeruginosa, the LuxR-type transcription factor RhlR controls virulence gene expression at high cell density, requiring its cognate acyl-homoserine lactone signal and the accessory protein PqsE for full activity. Here, we show RhlR abundance is controlled by ATP-dependent proteolysis through a self-limiting negative feedback loop. An N-terminal degron, protected by PqsE binding, is required for degradation by Lon and ClpP1/P2. Degron removal stabilizes RhlR, advancing QS-regulated promoter activation, enhancing biofilm formation, and imposing a competitive fitness cost. RhlR directly activates clpP2 transcription, creating feedback that limits its own accumulation. These findings reveal proteolytic turnover as an underappreciated regulatory layer of QS and suggest a mechanism for transitioning bacteria from high-cell density states.

Presenter(s): Gianna Mirabile

Showcase Advisor: Nicholas Mantis

Abstract: Complex pathogens like the causative agent of Lyme disease, Borrelia burgdorferi, elicit broad, highly reactive immune responses, including antibody swarms against multiple targets. Deciphering which antibody populations contribute to disease resolution is critical for vaccines and immunotherapeutics. A major reactive target is decorin-binding protein A (DbpA). Serological studies reveal strong, persistent levels of DbpA antibodies. To understand DbpA-antibody interactions, we characterized DbpA-specific human monoclonal antibodies (mAbs) from convalescent and actively infected patients. For the mAb F945, we demonstrate reactivity with DbpA α-helices 3 and 4 via light-chain dominant germline-encoded paratope, suggesting F945 arose early via extrafollicular pathway. Another mAb, Y14, isolated from skin infection has higher somatic mutation but binds the same epitope. Neither mAb was capable of protecting mice against infection. We conclude the antibody response to DbpA may be concentrated towards an immunodominant epitope but these antibodies fail to alter disease outcome and could possibly drive post-treatment sequelae,

Presenter(s): Yuexiao Tang

Showcase Advisor: Janice Pata

Abstract: DNA replication is a fundamental cellular process in all organisms. Gram-negative and Gram-positive bacteria possess different replisomes and replicate DNA in a somewhat different way. This is because Gram-negative bacteria have only one essential DNA replicative polymerase, but low-GC content Gram-positive bacteria have two, DnaE and PolC. PolC, the major replicative polymerase, cannot extend RNA primers directly. Thus, DnaE, playing an intermediate role, takes over RNA primers from primase (DnaG) but adds a limited DNA before handing off to PolC. The process of how DnaG and DnaE coordinate primer synthesis and why DnaE can accommodate both RNA and DNA primers still remain mysterious. To identify specific features that enable DnaE to bind with both DNA and RNA primers from structural perspectives, we have solved the structure of DnaE bound to DNA/DNA duplex and are currently determining the structure of DnaE in complex with RNA/DNA duplex to allow a direct comparison.

Presenter(s): Nora Whorton

Showcase Advisor: Melissa Prusinski

Abstract: Tick-borne diseases pose a significant public health concern in New York State. The New York State Department of Health (NYSDOH) has conducted both passive (1990-2011) and active (2008-present) tick surveillance. This project combines  retrospective analysis of passive tick surveillance data and active field surveillance using standard dragging surveys to assess tick trends in Western New York. Results show the emergence and establishment of Ixodes scapularis, the primary vector of disease-causing pathogens in Western New York which initiated the active tick surveillance to determine population density and pathogen prevalence in a standardized way.   22 sites across 12 counties were sampled, which resulted in the collection of 1,113 ticks. This project provides insight into decision making regarding different surveillance methods, their abilities to detect spatial and temporal trends in tick distribution as well as their role in guiding prevention and response strategies to emerging tick-borne disease risk.

Presenter(s): Ali Nwabuoku

Showcase Advisor: Rebecca McCarthy

Abstract: Biofilms are often described as a single, homogeneous entity; however, bacteria in different parts of a biofilm experience vastly different environments and, in turn, alter their cellular physiology. The microbial biofilm field has spent a great deal of time and energy to understand, at the single cell level, how a bacterium attaches to a surface, how a bacterium attaches to its neighbor, and how these interactions ultimately give rise to the overall structure of a biofilm. Our project aims to take a macroscopic, population-wide view of how bacteria respond to different environmental signals within the context of a colony biofilm, which is a biofilm grown on an agar surface with different nutrient gradients and oxygen availability.

Presenter(s): Jordene Wynter

Showcase Advisor: Todd Gray

Abstract: In the process of conjugation, DNA is transferred between two bacterial cells via direct physical contact. A unique form of conjugation called distributive conjugal transfer allows donor and recipient strains of the model mycobacterial species Mycobacterium smegmatis to exchange DNA, providing us with an experimental system to explore cell-cell interactions between mycobacteria. Our research aims to understand the regulatory functions of WhiB6, a signaling protein activated when conjugal mycobacteria cells have established physical contact. We hypothesize that a whiB6 neighboring gene produces a protein, EspM, that regulates whiB6 gene expression. This project seeks to investigate the relationship between EspM and WhiB6 within the conjugal signaling network. Genes previously identified as important for conjugation in this non-pathogenic model Mycobacterium have homologs that contribute to virulence in pathogenic mycobacteria. This suggests that our work may provide insights in pathogenic contexts and may unveil previously unknown aspects of bacterial communication and pathogenicity.