Department of Biochemistry and Molecular Biophysics

Author: Conrad Weiland

2024 News / All News

Congratulations to Jeramia Ory for being selected as a member of the WASHU Academy of Educators!

Jeramia Ory Congratulations to Jeramia Ory’s selection as a new member of the Washington University School of Medicine Academy of Educators! This achievement acknowledges significant contributions to education and recognizes their valuable place as a central contributor to the education mission of the School of Medicine.

The Academy of Educators received many applications for membership in the Academy. Each application was reviewed by one external and two internal peer reviewers. Ory’s application, letter(s) of support, CV and supporting documentation were scored by these three peers using our specific standards and criteria for membership, as delineated in the application review matrix. (more…)

All Research / Janetka Lab

Spotlight on Research – Janetka Lab

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.

All Research / Ghanbarpour Lab

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.

All Research / Li Lab

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.

All Research / Garcia Lab

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.

Adhikari Lab / All Research

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.

2024 Events / 2024 News / All Events / All News

2024 BMB SURGE Poster Session

Featured are six individuals chosen for the Department of Biochemistry & Molecular Biophysics’ Summer Undergraduate Group Experience (SURGE) program. Gavin Ghafoori (Dr. Hema Adhikari’s Lab), Alec Garasimowicz (Dr. Andrea Soranno’s Lab), Maxine Akunnakwe and Baika Erdenepurev (Dr. Natalie Niemi’s Lab), and Kylie Villadolid (Dr. Eric Galburt’s Lab) showcase their remarkable lab research during the annual SURGE poster session. These photos encapsulate the culmination of their dedicated 8-week journey of lab experience and study.

You can click here to view photos from the event.

All Publications / Janetka Publications

Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin

Matthew W Mahoney, Jonathan Helander, Anoopjit S Kooner, Mariah Norman, Vishnu C Damalanka, Paolo De Bona, Paulina Kasperkiewicz, Wioletta Rut, Marcin Poreba, Maithri M Kashipathy, Kevin P Battaile, Scott Lovell, Anthony J O’Donoghue, Charles S Craik, Marcin Drag & James W Janetka (2024). “Use of protease substrate specificity screening in the rational design of selective protease inhibitors with unnatural amino acids: Application to HGFA, matriptase, and hepsin” Protein Sci. 2024 Aug;33(8):e5110. doi: 10.1002/pro.5110. (Abstract)

All Publications / Li Publications

Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B

Meng Gao, Long Chen, Jinlong Yang, Shixia Dong, Qing Cao, Zihan Cui, Yanyan Dong, Hongli Liu, Yan Shen, Haiping Yang, Zhenyu Hao, Lei Zhang, Weikai Li, Jian-Ke Tie & Guomin Shen (2024). “Multimodal mechanisms of pathogenic variants in the signal peptide of FIX leading to hemophilia B” Blood Adv.2024 Aug 13;8(15):3893-3905. doi: 10.1182/bloodadvances.2023012432. (Abstract)