Category: All Research
All Research
The Janetka Lab specializes in the rational design, chemical synthesis and drug development of small molecule therapeutics. Our group uses a combination of medicinal chemistry, chemical biology, and biochemistry to investigate and validate new therapeutic targets. We utilize computational tools to improve inhibitors based on X-ray structures followed by optimizing compounds for drug-like properties. We work closely with biology collaborators to evaluate compounds for their biological activity in vitro and efficacy in animal models of disease. The ultimate goal of our work is the clinical development of innovative drugs. The lab currently works on inhibitors of various enzymes, receptors, and lectins (carbohydrate binding proteins) as new treatments for viral, bacterial, and parasitic infections as well as anticancer therapeutics to prevent metastasis.
Spotlight on Research – Ghanbarpour Lab
The Ghanbarpour Lab studies the breakdown of proteins in bacteria and human mitochondria by ATP-dependent AAA proteases and their cognate modulators. AAA proteases are crucial for removing unneeded or aberrant proteins, ensuring cellular health and shaping the proteome for specific cellular functions.
The selection of proteins for degradation is a sophisticated process, influenced by accessory modulators called adaptor proteins. Despite the importance of this mechanism and the role of adaptor proteins in protein degradation, the molecular details of these processes remain largely unknown.
Our research aims to decode the intricate mechanisms behind protease specificity and how adaptor proteins tailor these actions. We employ a multidisciplinary approach that combines in vitro reconstitution and biochemistry, structural biology (cryo-EM, cryo-ET, and crystallography), cellular assays, and pulse-labeled mass spectrometry to monitor degradation.
Our long-term goal is to enable the development of new therapeutics that can manipulate these protease-adaptor interactions, offering new ways to treat human diseases and fight bacterial infections.
The selection of proteins for degradation is a sophisticated process, influenced by accessory modulators called adaptor proteins. Despite the importance of this mechanism and the role of adaptor proteins in protein degradation, the molecular details of these processes remain largely unknown.
Our research aims to decode the intricate mechanisms behind protease specificity and how adaptor proteins tailor these actions. We employ a multidisciplinary approach that combines in vitro reconstitution and biochemistry, structural biology (cryo-EM, cryo-ET, and crystallography), cellular assays, and pulse-labeled mass spectrometry to monitor degradation.
Our long-term goal is to enable the development of new therapeutics that can manipulate these protease-adaptor interactions, offering new ways to treat human diseases and fight bacterial infections.
Spotlight on Research – Li Lab
The Li Lab studies the structure and function of integral membrane proteins, with a focus on ones that are important for hematologic and cardiovascular systems. We use a variety of structural biology, biochemistry, cell biology and mass spectrometry techniques to understand the structural mechanism of these membrane proteins. Structural insights give us a novel angle to elucidate the actions of these proteins in cellular settings. Deep understanding of protein structure and function often has implications significant for human disease. In addition, these proteins provide challenges that motivate us to develop new structural and biochemical methods broadly applicable to membrane biology.
Spotlight on Research – Garcia Lab
The Garcia Lab is focused on the development and application of quantitative mass spectrometry (MS) based proteomics and related computation for understanding dynamic protein and proteome post-translational modifications (PTMs). One particular interest is in investigating epigenetic histone PTMs and their role in regulating gene expression in normal and disease physiology. Our lab utilizes high resolution and high-throughput mass spectrometry and further develops improved sample preparation approaches and advanced instrument methods to sequence intact proteins (Top Down MS) and peptides (Bottom Up MS) with high sensitivity. All of these advances have been employed to study several epigenetic targets involved in processes such as cancer, neurological development, viral infection and cellular reprogramming.
Spotlight on Research – Adhikari Lab
The Adhikari Lab focuses on interrogating RAS oncoprotein signaling networks through the lens of interactomes in cancer, based on an innovative functional proteomics platform combining proximity labeling technology coupled to CRISPR/Cas9 screening. We employ a multifaceted approach by leveraging biochemistry, cell signaling, proteomics, genomics into a range of experimental systems including cell culture, three-dimensional organoids and genetically engineered mouse models. The overarching goal of our laboratory is to elucidate mechanistic underpinnings of reprogramming of oncoprotein signaling networks in space and time to transduce aberrant signaling and promote cancer initiation and tumorigenesis, as a discovery point to reveal new actionable targets that can counter therapeutic resistance.
Spotlight on Research – Holehouse Lab
The Holehouse Lab works to understand how intrinsically disordered regions – protein regions that lack a stable 3D structure – facilitate molecular and cellular function. The lab combines computational and experimental approaches to elucidate how disordered regions behave in isolation, how they interact with partners, how they evolve, and how mutations in disordered regions impact their normal cellular function in the context of human disease. The lab explores these questions in various contexts, combining synthetic biology and protein design to decode the underlying principles that relate sequence to function.
Spotlight on Research – Egervari Lab
The Egervari Lab’s goal is to elucidate how metabolic changes influence gene expression in the brain in physiological and pathological states. We combine state-of-the art proteomic, genomic and metabolomic approaches including on the single cell level, with quantitative and mechanistic studies, using disease-relevant in vitro and in vivo models. Our hope is that this work will identify new therapeutic targets for a variety of human diseases, and transform our understanding of how the brain adapts to environmental stimuli.
Spotlight on Research – Goo Lab
Young Ah Goo’s lab specializes in using mass spectrometry-based multi-omics to address biological questions, particularly the discovery of diagnostic and prognostic biomarkers and therapeutic targets for human diseases. She directs The Mass Spectrometry Technology Access Center, which supports advanced technologies in proteomics, metabolomics, lipidomics, and mass spectrometry imaging.
Spotlight on Research – Niemi Lab
The Niemi Lab investigates how mitochondria are built, regulated, and maintained across physiological contexts. We blend biochemistry, systems biology, and physiology to understand mechanisms of mitochondrial regulation and how they influence metabolism and organellar function. Using insights gained from our molecular studies, we aim to understand how mitochondrial dysfunction contributes to mammalian pathophysiology, with the long-term goal of translating our discoveries into new therapeutic options to restore mitochondrial function in human disease.
Mechanisms of mitochondrial biogenesis, regulation, and turnover.
Spotlight on Research – Greenberg Lab
The Greenberg Lab focuses on how cytoskeletal motors function in both health and disease. Currently, the lab is studying mutations that cause familial cardiomyopathies, the leading cause of sudden cardiac death in people under 30 years old. The lab uses an array of biochemical, biophysical, and cell biological techniques to decipher how these mutations affect heart contraction from the level of single molecules to the level of engineered tissues. Insights into the disease pathogenesis will guide efforts to develop novel therapies.