Research projects in the Systems Biology and Translational Medicine Laboratory of Akhilesh Pandey, M.D., Ph.D., focus on advancing precision medicine through the study of multi-omics, biomarkers, proteomics, and the molecular landscape of various diseases and conditions.
Novel therapeutic targets and medication resistance in multiple myeloma
Immunomodulatory imide drugs (IMiDs), such as the medications thalidomide, lenalidomide and pomalidomide, have been shown to be effective in treating multiple myeloma. Cereblon, a substrate adaptor module of E3 ubiquitin ligase, was identified as a target of IMiDs leading to inhibition of plasma cell proliferation. Still, resistance to IMiDs is a major challenge for care. Dr. Pandey and his research lab team are using a multi-omics approach to discover and validate biomarkers that can predict resistance to IMiD-based treatment.
Congenital disorders of glycosylation
Congenital disorders of glycosylation are a group of rare genetic disorders characterized by problems in cellular glycosylation machinery that affect the addition of glycans on to larger biomolecules, including proteins and lipids. More than 150 genes are known to be involved in glycosylation and may be affected in these disorders, with variable biochemical outcomes. As a result, genomic sequencing is often used to diagnose congenital disorders of glycosylation.
There are specific biomarkers for some subtypes of these genetic disorders, such as relative quantitation of glycosylated isoforms of transferrin in PMM2-CDG. But other types of congenital disorders of glycosylation would benefit from having more-specific biomarkers, including glycan, glycopeptide and glycolipid markers for diagnosis and treatment monitoring.
Our lab team has been identifying biomarkers and developing assays for several of these genetic disorders using mass spectrometry-based methods, including proteomics, glycoproteomics and glycomic analysis.
Cancer biomarker discovery
Our lab is applying proteomics technologies to identify biomarkers in various cancers, including bile duct cancer, pancreatic cancer and gallbladder cancer. Most diagnostic biomarkers for cancer in clinical use are glycoproteins. Using comprehensive glycoproteomics, we're discovering biomarkers that could be further developed into novel diagnostic tests for early detection of these tumors.
Single-cell DNA/RNA-seq has had a tremendous impact on biological research. But a corresponding technology for unbiased proteomic analysis of single cells is still lagging, mainly because of the lack of technology such as polymerase chain reaction (PCR) for amplifying proteins.
Dr. Pandey's lab is making significant efforts in every aspect of proteomic workflow. We're developing advanced sample processing techniques using state-of-the-art mass spectrometry instrumentation. We're using these cutting-edge single-cell proteomics methods to develop and deploy novel technologies to detect and quantify proteins from single cells or a limited number of cells, such as organoids and laser capture microdissected cells, from a variety of samples. These include primary cells, cell lines, organoids, fresh tissues and formalin-fixed paraffin embedded (FFPE) tissues on slides.
Mass spectrometry-based lipidomics and metabolomics
Lipids and metabolites are important chemical entities that are highly diverse in structure. They play essential roles in cellular functions. Our lab uses advanced high-resolution mass spectrometry to identify and quantify a vast range of lipids and metabolites. Our work is bridging lipidomics and metabolomics platforms with other omics technologies to identify novel biomarkers.
We're also studying spatial distributions of lipids and metabolites using imaging mass spectrometry. Investigating lipid and metabolite biology can reveal how lipids and metabolites are related to the development of certain conditions and diseases. In addition, our lab is creating a highly multiplexed mass spectrometry-based lipidomic assay that can measure about 2,000 lipid species from blood.