The Chemical Biology-focused research groups in CPB cover a variety of exciting research topics. All groups are currently recruiting postdocs.

The lab of Benjamin Barad seeks a postdoctoral scholar to investigate cytoskeletal reorganization during intracellular bacterial infection using cellular cryo-electron tomography. The scholar will receive training in sample preparation, tilt series collection, and data analysis for cryo-electron tomography, as well as development of computational tools for the quantitative analysis of membrane and filament organization. In addition to cryo-electron tomography, the project will incorporate correlative cryo-fluorescence microscopy as well as live-cell fluorescence microscopy. (barad@ohsu.edu; https://baradlab.com/; @tomo.science) 

The lab of Kimberly Beatty uses fluorescent probes to study the molecular basis of human diseases. Her lab investigates cellular protein organization across size scales and imaging platforms using novel genetic tags named VIP tags and is currently applied towards studying iron uptake and cancer signaling. In addition, her lab uses chemistry to study enzyme regulation and drug targets in Mycobacterium tuberculosis. (beattyk@ohsu.edu; www.beattylab.com; @beattylab)

The lab of Michael Cohen focuses on two main areas: (1) exploring new roles for nicotinamide adenine dinucleotide (NAD⁺) regulation in cells and (2) understanding the functions of post-translational modifications (PTMs) generated by NAD⁺-dependent enzymes. A major focus of our research is the evolutionarily conserved PTM, ADP-ribosylation, and its role in regulating cellular function and providing new opportunities for therapeutic development.

ADP-ribosylation is catalyzed by the PARP family of ADP-ribosyltransferases (17 members in humans), which transfer ADP-ribose from NAD⁺ to amino acids on target proteins. Most PARPs catalyze mono-ADP-ribosylation (MARylation), whereas four family members catalyze poly-ADP-ribosylation (PARylation).

Our lab has developed chemical tools and methods, including bumped NAD⁺ analogs, engineered enzyme pairs, and family-specific PARP inhibitors, to uncover PARP-mediated MARylation functions that are difficult to study with traditional approaches. Recently, in collaboration with the Pruneda lab (OHSU), we discovered a dual PTM called MARUbylation, in which ubiquitin is linked via an ester bond to protein-conjugated mono-ADP-ribose on glutamate or aspartate (Glu/Asp) residues. We found that MARUbylation can be extended with K11-linked polyubiquitin chains and occurs naturally in response to type I interferon signaling. We are now focused on defining the writer/reader circuitry that regulates MARUbylation and on understanding its functional consequences in cells.

Our research has led to numerous collaborations that leverage our selective inhibitors and chemical-genetic approaches to investigate how MARylation, and now MARUbylation, regulates protein function in cells and animal models. Together, these studies aim to uncover new mechanisms of cellular regulation and identify opportunities for therapeutic intervention.

(cohenmic@ohsu.edu; cohenlabohsu.com; @MichaelNADbio)

The lab of James Frank centers around cannabinoid receptors and how they are activated by their endogenous lipid ligands to affect biomolecule secretion in the brain and in the pancreas. The lab builds and evaluates new small molecule-based photoactivatable tools using chemistry, molecular biology, imaging, whole-cell electrophysiology, and in vivo behavioral experiments. (frankja@ohsu.edu, www.frank-lab.com, @jF-lab)

The lab of Braden Lobingier studies drug action at a family of signaling receptors called G protein-coupled receptors (GPCRs). We specialize in combining chemical biology with proteomic and genomic techniques to identify the mechanisms of receptor function. In addition, we have a parallel research program focused on understanding a critical organelle called the endosome. We seek to understand how the endosome specifically controls GPCR function as well as its role in controlling membrane proteins broadly. (lobingib@ohsu.edu; www.lobingierlab.com)

The lab of Carsten Schultz has a long-standing interest in chemical biology tool development with a focus on lipids and lipid signaling. We apply the tools from the chemistry bench to find the weak spot of virus infections and cancer progression. Specifically, we develop novel lipid tools to analyze lipid-interactomes in virus-infected cells and tissue samples from patients. We are interested in the mechanisms of intracellular lipid metabolism and trafficking. The lab uses a combination of organic chemistry, molecular biology, and live-cell and tissue slice imaging. We collaborate with virologists and omics specialists, and we aim to translate our findings into novel therapeutics via entrepreneurial activities. (schulcar@ohsu.edu)

The lab of Francis Valiyaveetil is interested in the molecular structure and function of ion channels and transporters. The lab combines structural with functional studies and investigates protein dynamics using fluorescence spectroscopy. (valiyave@ohsu.edu)

The lab of Xiangshu Xiao is interested in developing small molecule inhibitors and next-generation degraders of various nuclear proteins for cancer chemical biology. His lab combines organic chemistry, medicinal chemistry and pharmacology to expand the druggable genome for both mechanistic biology studies and cancer therapeutics.
xiaoxi@ohsu.edu | Xiao Lab

The lab of Bingbing Li focuses on developing novel cancer therapies, particularly for clear cell sarcoma of soft tissue (CCS), a rare and aggressive fusion-driven cancer. In parallel, the lab investigates the fundamental mechanisms of targeted protein degradation, with the goal of advancing the development of next-generation therapeutics.
lib@ohsu.edu

For more general information about the Chemical Biology Program or opportunities within CPB, please contact Carsten Schultz (schulcar@ohsu.edu). If you are interested in a particular topic or group, please contact the PI directly.

The Barad lab seeks a curious research assistant to support investigations into membrane reorganization during bacterial infection using cryo-electron tomography inside mammalian cells. In this role, the research assistant will be performing mammalian cell culture and performing bacterial infections in preparation for light microscopy and electron microscopy experiments, freezing and clipping electron microscopy grids, and performing cryo-light microscopy and focused ion beam milling to prepare thin vitrified samples for tomography. Interested applicants may also learn computational approaches for processing and analyzing 3D tomographic data with the goal of understanding protein structure as well as cellular organization in greater detail. (barad@ohsu.edu; https://baradlab.com/; @tomo.science).