| Summary Description: Columbia University's Department of Medicine invites applications for a research position in the rank of Postdoctoral Research Scientist at The Columbia University Irving Medical Center in the Division of Molecular Medicine in the Laboratory of Dr. Ira Tabas. The position includes both laboratory and translational research. Summary Description: Our laboratory studies the cellular biology of cardiometabolic disease, with an emphasis on the molecular-cellular mechanisms of advanced atherosclerosis and hepatic insulin resistance and non-alcoholic steatohepatitis (NASH) in obesity, and the links between these processes. We are seeking a talented postdoctoral research scientist with interest and expertise in molecular-cellular mechanisms related to cardiometabolic disease, insulin resistance, and NASH, including metabolic studies in obese diabetic mice. Priority will be given to candidates who have experience in these areas, particularly in conducting metabolic analyses in obese mice. The selected candidate will work conduct research on the following projects:
Advanced atherosclerosis have focused on integrated processes that combine to promote advanced plaque progression, with the current focus on defective clearance of the apoptotic cells (efferocytosis) and impaired inflammation resolution. In the efferocytosis field, we study (a) a macrophage receptor called MerTK; and (b) a process called high-burden efferocytosis, whereby a macrophage ingests and degrades multiple apoptotic cells over a short time period, requiring reprogramming of vesicular trafficking pathways and metabolism of molecules from degraded apoptotic cells. The inflammation resolution project investigates cellular mechanisms of the resolution process and its therapeutic potential, e.g., through the use of atherosclerosis-targeted nanoparticles packaged with resolution mediators. An exciting new area in the lab involves identifying specific mechanistic links between impaired resolution pathways and clonal hematopoiesis of indeterminate potential (CHIP), which is a major risk factor for atherosclerosis and coronary artery disease in humans over the age of 60.
The lab’s studies on hepatic insulin resistance, which is an important driver of atherosclerosis, led to the discovery of a new calcium-stimulated pathway in hepatocytes that plays a key role in glucagon-mediated excessive glucose production, insulin resistance, fatty liver, dyslipidemia, impaired thrombolysis, and adipose tissue inflammation in the setting of obesity and type 2 diabetes. Ongoing studies are investigating: (a) the detailed molecular mechanisms involved in this new pathway; (b) how the pathway may promote atherosclerotic plaque progression by affecting plaque macrophages; and © strategies to translate our discoveries into new types of drugs to treat type 2 diabetes and prevent diabetes-driven atherosclerotic plaque progression.
The lab's study also interests in roles of different cell types of liver in NASH development and progression, with current investigations focused on (a) the role of a transcription factor TAZ in both NASH fibrosis and NASH-associated hepatocellular carcinoma; (b) new mechanistic insight into human genetic risk factors for NASH fibrosis, with current focus on MERTK and PNPLA3; © mechanisms of efferocytosis in NASH; and (d) new therapeutic strategies to prevent steatosis-to-NASH progression based on our findings. |
