CPRI COBRE Projects
Current Projects
Dysregulation of bile acid homeostasis in obesity pathogenesis
Lindsay Czuba, Ph.D.
Assistant Professor, Department of Pharmaceutical Sciences
February 2024 - present
Progressive human obesity is associated with systemic dysregulation of cholesterol, oxysterol, and bile acid homeostasis and is a leading cause of NAFLD, diabetes, and cardiovascular disease. Bile acids and their metabolites serve as ligands for nuclear receptors such as the farnesoid X receptor (FXR) and liver X receptor (LXR) to transcriptionally regulate lipid and cholesterol homeostasis. Gut commensal bacteria contribute significantly to the metabolism of bile acids to produce secondary bile acid metabolites. However, little is known about the individual contributions of bile acids and their secondary metabolites to gut-liver signaling and metabolic effects. Early work in the lab aims A) to identify the affinity and activity of secondary bile acid metabolites towards FXR and the bile acid transporter, ASBT and B) to develop LC-MS/MS methods to quantify bile acid metabolites and oxysterols in gut and liver tissue. Findings from these projects will provide foundational knowledge on the role of bile acid metabolites in mediating bile acid, cholesterol, and lipid homeostasis and inform future translational research on human obesity pathogenesis and its metabolic comorbidities.
Mentors: Barbara Nikolajczyk, Bjoern Bauer
Elucidating the chemical biology of the druggable targets in enteric pathogens C. jejuni and E. coli
M. Ashfaqul Alam, Ph.D.
Assistant Professor, Department of Microbiology, Immunology, & Molecular Genetics
July 2023 - present
This proposal’s objective is to elucidate the chemical biology of microbial metabolites and small molecules to specifically target intestinal pathogens, which cause intestinal infection & inflammation. The findings will facilitate the development of intervention strategies to specifically control the emergence and spread of antibiotic resistance in this significant human pathogen without altering the entire gut microbiota.
Mentors: Qing-Bae She, Samuel Awuah
Former Projects
Developing immunotherapeutic nanoparticles for spinal cord injury
Jonghyuck Park, Ph.D.
Assistant Professor, Pharmaceutical Sciences
March 2022 - March 2024
Traumatic spinal cord injury (SCI) leads to primary injury, followed by secondary injuries including inflammation which create an inhibitory environment. Particularly, the SCI demographic shifts toward a more equal balance among males and females, indicating that improved therapeutics are needed since the difference in physiological factors between sexes play important roles in pharmacological treatments and functional recovery after SCI. In this study, Poly(lactide-co-glycolide) (PLG)-based multiple nanoparticle (NP) formulations will be designed with various physicochemical factors to identify sex-specific key functionality of NPs to reprogram inflammation, thereby facilitating functional recovery in both sexes after SCI. Dr. Park’s study will provide a potentially practical therapy for the entire SCI population.
Mentors: John Gensel, Dave Feola, Martha Grady
Immunomodulatory therapy for bone regeneration
Ramkumar Annamalai, Ph.D.
Assistant Professor, Department of Biomedical Engineering
March 2021-August 2023
Inflammation plays a vital role in conditions that affect bone formation, resorption, and fracture healing. The majority of the work on macrophage response, in the context of bone regeneration and fracture healing, has focused on activation mediated by biochemical signals. The physical parameters of the fracture microenvironment, especially matrix mechanics and their influence on macrophage immunophenotypes, are largely overlooked and potentially critical to the healing process. Dr. Annamalai’s research program aims to elucidate the cytoskeleton-driven transcriptional control of macrophage phenotype and function during bone fracture and engineer next-generation immunomodulatory biomaterials for therapeutic bone regeneration.
Mentors: Val Adams, Daniel Pack, Vincent Venditto, Chang-Guo Zhan
Chemical biology of microbial type IV secretion systems
Carrie Shaffer, Ph.D.
Assistant Professor, Department of Veterinary Science
March 2020 - January 2023
Many important bacterial pathogens use a specialized molecular machine known as the type IV secretion system (T4SS) to deliver diverse virulence factors into target host cells. Dr. Shaffer's proposal seeks to develop robust molecular tools to accelerate the fundamental study of T4SS function, and will determine how a gastric cancer-associated T4SS assembles to transport carcinogenic microbial cargo into human cells. Success of the proposed research will advance the Shaffer lab's understanding of mechanisms underlying T4SS activity, and will stimulate the development of selective therapeutics that target the T4SS nanomachine.
Mentors: David Burgess, Konstatin Korotkov, Brian Stevenson, Sylvie Garneau-Tsodikova, David Watt
Quantitative mechanical phenotyping of bacterial biofilms on implant surfaces
Martha Grady, Ph.D.
Associate Professor, Department of Mechanical Engineering
March 2020 - January 2022
Millions of Americans have undergone procedures that require either temporary or permanent placement of a medical device or implant. Bacterial biofilms play a significant role in hospital-acquired infections at these medical device interfaces. Dr. Grady's research program aims to first understand therapeutic-resistant biofilm infections and second, to decrease propensity for their genesis by developing protocols for mechanical phenotyping of biofilms associated with device-related infections
Mentors: Dave Feola, Chris Richards, Steven Van Lanen, Jon Thorson
Gold-based pharmacophore synthetic strategies as a basis for transcription factor modulator discovery
Samuel Awuah, Ph.D.
Assistant Professor, Department of Chemistry
March 2020 - August 2021
Synthetic molecules for site-selective chemical modification of proteins expands their functional and therapeutic utility. Current technologies for protein modification can achieve site-selective conjugation but require extensive sequence engineering or limited in scope. Dr. Awuah's proposal aims to resolve this problem by developing a gold-based pharmacophore platform for site-selective protein modification that target a broad range of nucleophilic amino acid side chains toward selective disruption of protein-protein interactions.
Mentors: Edith Glazer, Jill Kolesar, Mark Leggas, Jurgen Rohr
Understanding the role of anti-apolipoprotein A-I antibodies in atherosclerotic cardiovascular disease
Vincent Venditto, Ph.D.
Assistant Professor, Department of Pharmaceutical Sciences
March 2020 - December 2020
Dr. Venditto’s research program seeks to investigate the antibody response targeting apolipoprotein A-I by implementing novel strategies to modulate epitope-specific immune responses in mice and characterize the molecular components of this response to gain mechanistic insight into their role in disease progression. These objectives will improve our understanding of the immune response associated with atherosclerosis and promote the identification of novel therapeutic targets. These data will guide future efforts to develop novel peptide and protein therapeutics to reduce the cardiovascular disease burden in patients.
Mentors: Val Adams, Greg Graf, Chang-Guo Zhan, Nancy Webb
