How do metabolites function as signaling molecules independent of their metabolic pathways

Metabolites and other small molecules often accumulate during diseases, such as cancer, infection, and inflammation.  Their roles as metabolic substrates have been studied for over a century.  While studies have focused on their known roles as metabolic substrates in cancer and other diseases, we propose that, independent of their metabolic pathways, metabolites function as critical signaling molecules for cell-cell communication.  Using questions guided by human patient data, we conduct hypothesis-driven research through a combination of in vitro and in vivo models.  We collaborate with biochemists and structural biologists to develop new methods to study protein-metabolite interactions. 

Cancer and Inflammation are diseases of abnormal cell growth, proliferation, and signaling which are dependent on extracellular nutrients and instructions.  While metabolites serve as nutrients, they are foremost small molecules that are capable of directly regulating protein function thereby serving as signaling moleculesWe aim to provide insight into cancer and cell biology by studying the mechanisms of how small molecule metabolites directly regulate cellular growth, proliferation, and signal transduction independent of their known metabolic pathways

Allosteric regulation of mitochondria metabolism and innate immune signaling. 

Lactate is the second most abundant circulating carbon and is often elevated in cancer and other diseases.  While most studies focus on its known metabolic functions, we recently found that lactate is also a mitochondrial signaling molecule.  Using a combination of genetic CRISPR screening, protein mass spectrometry, cell biology and biochemical approaches, we are dissecting the mechanisms by which lactate and other monocarboxylates signal to the mitochondria.  

Metabolic signaling as a regulator of cell fate decision.

Infectious and commensal bacteria collectively outnumber host cells.  They produce metabolites that are typically not metabolized by the host.  We hypothesize that these small molecules serve essential signaling functions, either as pro-inflammatory or disease tolerance molecules, and can provide insight into how small molecule signals alter protein functions in general.  We are using in vitro and in vivo systems to characterize the signaling functions of bacterial metabolites in cell proliferation, differentiation, and signaling. 

From bench to bedside: guided by clinical questions

As a physician-scientist who also treats patients with central nervous system tumors and conditions, I'm passionate about studying questions driven by clinical observations from patients.  We use clinical observations to generate testable hypothesis that can be dissected using a combination of tissue culture, biochemistry, molecular and cell biology, and mass spectrometry assays.  We also collaborate with the Siqi Liu lab, Zhijian Chen lab, Javier Garcia-Bermudez lab, and Stephen Chung lab to develop new in vitro and in vivo methodologies.