Catalyst Award Program Recipients
2022 Catalyst Award Recipients
Edwin Chen is a postdoctoral fellow in the lab of Dr. Matt Culyba within the Division of Infectious Diseases at the University of Pittsburgh School of Medicine. Edwin is supported by the NIH-funded University of Pittsburgh T32 Training Program in Antimicrobial Resistance. He received his MD and PhD in Molecular Microbiology in Dr. Niraj Tolia’s lab at Washington University in St. Louis where his research was focused on structural vaccinology of Plasmodium invasion proteins.
Methicillin-resistant Staphylococcus aureus (MRSA) is commonly found in healthcare facilities and invasive MRSA infections are associated with high morbidity and mortality. Clinically persistent MRSA infections occur despite use of active antibiotics and are associated with mutations that constitutively activate the stringent response, a highly conserved bacterial stress response that enhances survival to antibiotics while simultaneously restricting cellular growth. Activation of the stringent response is a double-edged sword whereby bacteria must balance competing effects of increased survival and decreased growth. In our recent study of within-host evolution of methicillin-resistant S. aureus (MRSA) in persistent bacteremia, we identified clinical strains that contained activating mutations in rel, the central stringent response regulator, yet only display subtle growth defects. Within these same clinical strains, we find concurrent mutations in fusA and infB, key regulators of the cellular translational machinery, and who also happen to be directly regulated by the stringent response second messenger molecule, (p)ppGpp. We therefore hypothesize that while activation of the stringent response enhances survival to antibiotics, once the environmental stressor is removed, it subsequently impresses upon the cell a selective pressure to evolve compensatory mutations to escape from its growth-limiting effects. This grant will help fund studies to explore the fitness landscape of stringent response activation and shed light into how S. aureus may adapt to, and escape from, pressures within the host.
Alecia is a PhD candidate in the laboratory of Dr. Vaughn Cooper in the Microbiology and Molecular Genetics Department at the University of Pittsburgh. Alecia received her Bachelor of Science in Biology from Lehigh University, where she did undergraduate research in the laboratory of Dr. Gregory Lang studying intracellular viruses of yeast. Alecia joined the Program in Microbiology and Immunology at Pitt in 2019 and has been extremely active in the program, serving on the Admissions Committee and as a program representative for the Biomedical Graduate Student Association. She is also active in the EvolvingSTEM program, a hands-on curriculum for local high school students that is designed to motivate interest and understanding of evolution and the scientific method. In her free time, Alecia enjoys cooking, crochet, and exploring the outdoors with her two dogs.
Alecia is passionate about research at the interface of evolutionary biology, microbiology and bacterial pathogenesis, and public health. Her graduate work focuses on the role of evolutionary history in promoting or constraining antimicrobial resistance (AMR) in the high priority pathogen Acinetobacter baumannii. AMR is a global and leading challenge of evolutionary medicine and is associated with nearly 5 million deaths per year. She is studying how strain history and genetic background influence the predictability of phenotypes and genotypes causing AMR in A. baumannii clinical isolates. Resistance evolves de novo in diverse species and strains by incompletely understood mechanisms that interact with the genome and history of the strain. AMR is a function of both recent selection and deep evolutionary history; this complexity obscures understanding of genotype-phenotype relationships and limits resistance prediction from genome sequences. The Catalyst Award will support a branch of Alecia’s thesis work where she aims to better understand the genotype-phenotype map of A. baumannii AMR. A more comprehensive understanding of the genetic causes for virulence and AMR phenotypes will increase resistance predictability, which may improve clinical outcomes of patients infected with multidrug-resistant (MDR) bacteria.
2020 Catalyst Award Recipients
James (Jimmy) Budnick is a second year postdoctoral fellow in the lab of Dr. James Bina within the Department of Microbiology and Molecular Genetics at the University of Pittsburgh School of Medicine. Jimmy is supported by the NIH-funded University of Pittsburgh Training Program in Antimicrobial Resistance (TPAR) in the Department of Medicine. He received his Ph.D. in Biomedical and Veterinary Sciences in Dr. Clayton Caswell’s lab at Virginia Tech where his research was focused on characterizing mechanisms of transcriptional regulation in the bacterial pathogens Brucella abortus and Agrobacterium tumefaciens.
The emergence of multidrug-resistant (MDR) Enterobacteriaceae has been identified as an urgent human health threat by the CDC and the WHO. This is partially due to the high mortality rate of infected patients, which has been reported to be as high as 50% for infections caused by carbapenem-resistant Enterobacteriaceae (CRE). A significant percentage of all CRE infections are caused by the pathogen Klebsiella pneumoniae (Kpn), an opportunistic Gram-negative bacterium that causes myriad infections, ranging from pneumonia to pyogenic liver abscess. While Kpn can horizontally acquire resistance genes on plasmids and other mobile elements, the core genome also contains genes providing intrinsic antimicrobial resistance, which are underexplored compared to acquired mechanisms. I’ve utilized an in vitro evolution approach to identify novel mechanisms of resistance by exposing Kpn to different concentrations of antibiotics and then detecting genetic variants within the genomes of evolved populations. My hypothesis is that these genetic variants are located within intrinsic resistance genes that are critical for both the evolution of MDR phenotypes and the ability of Kpn to cause disease (i.e. Kpn pathogenesis). My project focuses on understanding the evolutionary trajectory of the evolved populations when exposed to antibiotics as well as elucidating the contribution these novel markers to resistance, physiology, and virulence in Kpn to reveal their potential as targets for antimicrobial intervention.
Amanda Kowalczyk is a PhD candidate in the Clark and Chikina labs through the Carnegie Mellon University-University of Pittsburgh joint PhD program in Computational Biology. Her research focuses on using comparative genomics strategies to link convergently-evolving phenotypes in mammals to their associated genes and regulatory elements. Outside of her research, Amanda is actively involved in outreach efforts in the greater Pittsburgh area and beyond, including participating in the Letters to a Pre-scientist program, co-organizing the TECbio REU at the University of Pittsburgh, and founding the Greensburg Salem High School Outreach Program. She is also an avid writer and regularly publishes science blogs through popular online forums to help make science accessible to the general public.
As sequencing technology improves, new high-quality genomes are increasingly available to investigate the genetic basis of traits. One useful tool to connect traits to their associated genetic drivers is convergent evolution. When unrelated species independently develop a trait, they may also experience similar evolutionary changes in genes and regulatory elements related to that trait. Thus, by seeking concordance between sequence evolution and trait evolution, genetic elements can be linked to traits. I focus on studying convergently evolving traits relevant to human health, such as longevity, hairlessness, and vision. By studying the genetic changes underlying those traits across all mammals, I can better understand their genetic basis in humans. I will use the Catalyst Award to investigate putative regulatory elements associated with eye development that were previously discovered using signals of sequence convergence in blind subterranean mammals. Candidate regions will be tested to determine expression levels across different cell types in the developing mouse retina. In tandem, candidate regions will be scanned for potential causative mutations in human patients with congenital blindness and no known causative mutations in coding sequence. Together, these pieces of evidence will help define the regulatory landscape underlying vision.
2019 Catalyst Award Recipients
Steve Sanders is a postdoctoral associate in the Nicotra lab at the Thomas E. Starzl Transplantation Institute at the University of Pittsburgh. Throughout his career he has focused on developing the colonial marine cnidarian, Hydractinia, as a model system for biological and medical research. He received his doctorate from the Dept. of Ecology and Evolutionary Biology at the University of Kansas. His dissertation research used Hydractinia (and a closely related species) to explore how changes in gene expression over evolutionary times scales mold and shape phenotypic evolution. As a postdoc in the Nicotra lab his research has been centered around allorecognition in Hydractinia and exploring its evolutionary links to innate immunity in vertebrates.
Transplantation is a life-saving procedure and the only cure for many diseases. Unfortunately, the immunosuppressive drugs that allow a transplant patient to tolerate a donated organ have toxic side effects and lead to increased mortality due to infection or malignancy. New drugs are therefore needed. This Catalyst Award will enable me to take an evolutionary approach to the discovery of new immune pathways that could serve as novel targets for immunosuppressive drugs.
My main objectives is to elucidate the signaling pathways that control allorecognition in a colonial marine invertebrate called Hydractinia. In a phenomenon analogous to the way a transplant patient’s immune system accepts or rejects a graft, individual Hydractinia can distinguish themselves from other members of their species via via cell-cell contact. This process is called allorecognition and is controlled by two transmembrane proteins, Alr1 and Alr2. Both have extracellular binding domains and relatively large cytoplasmic tails that bear putative immune signaling motifs. I will use various methodologies (including yeast-two-hybrid screen, immunoprecipitation, and heterologous in vitro assays) to identify the Hydractinia allorecognition signaling pathway(s) and then search for homologous pathways in vertebrates. These results will lay the foundation for future studies for allograft tolerance in a mammalian transplant model and could lead to the discovery of pathways that play previously unknown or unappreciated roles in the alloresponse.
Jenny Jones is a second-year postdoctoral fellow in the Lakdawala lab in the Department of Microbiology and Molecular Genetics. Her research is focused on understanding the process of packaging influenza virus genomic segments into fully infectious virus particles. She is also an active advocate for postdoctoral researchers at the University of Pittsburgh as the Networking Chair of the University of Pittsburgh Postdoctoral Association and as a postdoctoral representative in the University Senate. In her free time she enjoys making music, art, and writing.
The influenza virus genome is segmented and must undergo assembly prior to virus budding and release from an infected cell. Genomic assembly is an important bottleneck for reassortment, a process in which genetic material is exchanged between two influenza virus strains. Thus, understanding how assembly occurs is essential to combating influenza virus pandemics. If assembly is coordinated and non-random, then it stands to reason that genomic segments coevolve to maintain packaging compatibility. The Catalyst Award is being used to explore this possibility. Using a highly multidisciplinary approach, we seek to explore influenza packaging constraints by studying evolutionary relationships between genomic segments. We are first defining coevolutionary relationships between segments using computational biology and bioinformatics approaches. We are coupling these techniques with molecular methods, including fluorescence in situ hybridization, to visualize interactions between genomic segments within an infected cell. Ultimately, we seek to delineate the order in which influenza virus genomic segments assemble.