Laura L. Kiessling

Massachusetts Institute of Technology

Laura Kiessling is an institute member of the Broad Institute of MIT and Harvard, a member of Koch Institute for Integrative Cancer Research at MIT, and the Novartis Professor of Chemistry at MIT. Prior to MIT, she was the Laurens Anderson Professor of Biochemistry and the Hilldale Professor of Chemistry at the University of Wisconsin, where she also directed the Keck Center for Chemical Genomics. She has received a MacArthur Foundation Fellowship (1998) and a Guggenheim Foundation Fellowship (2008). In 2018, Kiessling was the first woman to receive the Tetrahedron Award. Kiessling is a Fellow of the American Academy of Arts and Sciences (2003), a Member of the American Academy of Microbiology (2007), the American Philosophical Society (2017), and the National Academy of Sciences (2007). In 2005, Kiessling was recruited by the American Chemical Society (ACS) to serve as the founding Editor-In-Chief of ACS Chemical Biology. In that role, she pioneered a new type of journal for ACS, one that now serves as the model for all ACS journals. Her efforts resulted in ACS Chemical Biology receiving the 2007 Award for Innovation in Journal Publishing from the American Publishing Association – the first time in more than 20 years that an ACS journal was honored for its innovation.

Kiessling began her undergraduate studies at UW-Madison but transferred to MIT after spring break trip to Boston, because she saw so many women excelling in science there. She earned her BS in Chemistry from MIT where she carried out research into asymmetric organic transformations with Professor Bill Roush. She followed her interest in organic synthesis to Yale, where she worked in the group of Stuart Schreiber. Her graduate research laid the foundation for the group’s synthesis of the ene-diyne core natural product calicheamicin γ, a DNA-cleaving compound with anticancer activity. She postulated that the sugars of this natural product were critical for DNA recognition, a hypothesis that was later borne out in subsequent research by the Danishefsky and Kahne groups. Kiessling’s interest in DNA recognition led her to postdoctoral studies at Caltech with Peter Dervan. There she synthesized the first non-natural bases to recognize mixed DNA sequences via triple helix formation.

Kiessling’s graduate and postdoctoral studies sparked an interest in understanding the recognition mechanisms of glycans. Because individual protein-glycan interactions are weak (Kd 10-3 M), she sought to understand and leverage multivalency to explore these processes. She recognized that defined multivalent ligands could serve as mechanistic probes and leads. Her approach to generate such ligands was to use controlled living polymerizations, such as the ring-opening metathesis polymerization (ROMP). Indeed, she was the first to use ROMP to synthesize bioactive polymers. She also pioneered the concept of “post-polymerization modification” to generate a series of polymers whose activities can be compared directly.

Kiessling used her access to synthetic ligands to show that low affinity, multivalent binding interactions can be remarkably specific. She also showed that multivalent ligands generated through this method could mimic mucins, and she generated the most potent ligands known for L-selectin, a protein involved in the inflammatory/immune response. Kiessling recently exploited steric A strain to control a polymer backbone to mimic the extended structure of mucins. Her mucin surrogates have multiple applications, including as agents to mitigate dry eye or to control the gut or vaginal microbiome.

Kiessling studies of multivalent recognition led her to introduce the concept of using bifunctional ligand to recruit natural antibodies to cells for destruction of tumor cells. In addition, she has shown that virus-like particles can be adorned with glycans to deliver antigens to dendritic cells. The result is an anticancer (Th2) immune response.

Kiessling extended her studies of multivalency in protein–glycan interactions to control over signal transduction. She synthesized and deployed multivalent chemoattractants to show that the bacterial chemosensors function in an array and thereby act as a kind of “nose” to sense and respond to attractants. She subsequently designed and leveraged multivalent arrays for human pluripotent stem growth. Her identification of heparan binding surfaces is the basis for a commercial platform and was highlighted to Congress by the NIH as an example of basic research yielding practical benefits.

In summary, Kiessling’s interdisciplinary research has elucidated and exploited the mechanisms of cell surface recognition processes. She has pioneered the synthesis of multiple types of molecular arrays and used them to elucidate the principles underlying multivalent interactions. She leveraged these findings to achieve cell specific recognition, elicit and illuminate mechanisms underlying signal transduction, and direct cell fate.