Cancer Center Member
Xiaolin He, PhD
Associate Professor, Molecular Pharmacology and Biological Chemistry; Feinberg School of Medicine
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Cancer Focused Research:
We focuses on cancer- and neural development-related structural mechanisms, especially on how extracellular signals (e.g., growth factors, adhesion molecules and morphogens) are translated into intracellular signals by the plasma membrane receptors. The methods used in our lab include, but are not limited to, high-resolution X-ray crystallography, biophysical definition of physiological states and binding processes (e.g., calorimetry, surface plasmon resonance, and analytical ultracentrifugation), and a variety of biochemical and cellular assays (e.g., pull-down, immunoprecipitation, cell growth, migration and morphology, and enzymatic assays). Our current research topics include receptor tyrosine kinases, semaphorin and its receptors, and synaptic adhesion molecules.
Our research on the class III, or the PDGFR family, of receptor tyrosine kinases (RTKs), including KIT, FMS, FLT3, PDGFR-a, and PDGFR-b, has shed light on the specific geometry, diverse recognition schemes, and regulation of this prototypic group of RTKs, all of which are directly involved in tumorigenesis.
The recent structure determination of the Semaphorin-Plexin complex in our lab has opened up several important questions pertaining to both angiogenesis (normal and cancer-related) and axon guidance as in the vascular and neural systems. The first question is how the complex spectrum of specificities are encoded between the eight families of Semaphorins and four families of Plexin receptors, to guide repulsive signaling in most cases but potentially lead to attractive signaling in other cases. The second question is how Neuropilins, the co-receptors, selectively participate in the regulation and assembly of class 3 Semaphorin signaling, which involve the largest families of both Semaphorins and Plexins. The third question is how the quiescent state of plexin is achieved via auto-inhibition, and how it is transformed into the active conformation upon ligand stimulation.