Kai Wen Teng's research while affiliated with NYU Langone Medical Center and other places

... Human malignancies are often linked to the activation of missense mutations of RAS genes (KRAS, HRAS, and NRAS), which are crucial in oncogenic transformation [28]. Due to the absence of binding sites appropriate for small-molecule inhibitors, oncogenic RAS proteins have long been thought to be undruggable [29]. Most KRAS mutations occur at codon 12, where G12D mutations account for the largest frequency (35%), followed by G12V (20-30%), G12R (10-20%), Q61 (~5%), G12C (1-2%), and other uncommon mutations. ...

... Our laboratory has also identified an adnectin-based molecule that binds to the breast cancerassociated protein PPM1D, a metal-dependent protein phosphatase [43]. Unlike antibodies, adnectin does not contain disulfide bonds, suggesting that it allows for expression and function in the cytoplasm, which is a reductive environment [44][45][46]. Taken together, the antibody-mimetic molecule adnectin can be used to recognize intracellular targets, unlike antibodies, and may be useful for the development of lead compounds as diagnostic and therapeutic agents, not only in vitro but also in vivo. ...

... Protein preparation, monobody development, biophysical characterization, and crystal structure determination were performed essentially as described previously (13,25). Deep mutational scanning was performed following published methods (21,26). ...

... These results suggest an important role for apo Ras in cell signaling. Indeed, recent work suggests that apo Ras may represent a tractable target to inhibit a subset of oncogenic Ras mutants [28]. ...

... This is in stark contrast to prior research suggesting that V600E BRAF mutations are a biologic contraindication to surgery for patients with otherwise resectable disease [43]. Finally, drug development may certainly benefit from a deeper understanding of somatic mutations; for example, agents targeting KRAS mutations are an area of active research [66][67][68][69][70][71][72][73][74]. ...

... Blockade of SARS-CoV-2 viral entry through the ACE2 receptor is largely mediated by immunoglobulins targeting the spike protein and its RBD component. [26][27][28] Here, we assessed . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. ...

... We also implemented a more rapid method for profiling the accessibility of SHP2 PTP by the monobodies using bead-based capture and detection using flow cytometry. 50,51 In this method we captured SHP2 from lysates using Mb11 or Mb13 immobilized on magnetic beads. After washing the beads, captured SHP2 was detected using an anti-SHP2 antibody followed by a fluorescently labeled secondary antibody. ...

... When we examined the binding region distribution of the serum antibody clonotypes at M1, we noticed that an unexpectedly high number of serum IgG clonotypes were categorized as iso-RBD across the four subjects (on average 49±11%), whereas S-RBD and S-non-RBD clonotypes comprised 17±3% and 34±10%, respectively (Fig. 1D). This observation was surprising to us because such high prevalence of iso-RBD antibodies in sera has not been reported before, although a couple of studies have shown examples of monoclonal antibodies (mAbs) identified through phage panning from synthetic and alpaca-derived antibody libraries that bind to recombinantly expressed soluble RBD but not to prefusion-stabilized S (91,92). We considered the possibility that these iso-RBD antibody clonotypes may be low in abundance and were not detected in the eluate of prefusion-stabilized S pulldown due to limitations in the detection sensitivity of Ig-Seq. ...

... SHP2 inhibition has shown synergy with KRAS G12C inhibitors [72,73]. SHP2 inhibition prevents the action of SOS1/2, increasing the amount of the GDP-bound state of KRAS G12C which is the target of KRAS inhibitors [74]. This is supported by the findings of KRASamplified cancer cell lines exhibiting increased sensitivity to SHP2 inhibition [72,75]. ...

... Lentiviral pseudotypes provide a rapid and accurate means to assess spike protein function. Neutralizing antibody titers determined by lentiviral pseudotype assays closely mirror those measured by live SARS-CoV-2 assays (38). To analyze the functional properties of the spike protein variants, we constructed cytomegalovirus (CMV) promoter-driven expression plasmids encoding the B.1.1.7, ...