SIMON KNOTT LABORATORY
Simon received his PhD from the Department of Molecular and Computational Biology at the University of Southern California, with Dr. Oscar Aparicio and Dr. Simon Tavaré acting as his mentors. Subsequently, he joined the laboratory of Dr. Gregory Hannon at Cold Spring Harbor Laboratory. In the Hannon lab, he developed computational and molecular tools to study gene function in mammalian cells. In addition, he applied these tools to identify novel drivers of breast cancer progression. Now, as the Principal Investigator of the Knott lab, Simon leads the our team. He is an Assistant Professor of Biomedical Sciences at Cedars Sinai Medical Institute and he also serves as the Assosicate-Director of the Center for Bioinformatics and Functional Genomics.
In August 2016, the Knott lab was formed at Cedars-Sinai Medical Center in Los Angeles, California. Here, we aim to develop therapies that target the intercellular relationships within tumors that promote progression and resistance to current and experimental therapies.
DRUG DISCOVERY: PAST, PRESENT AND FUTURE
The “war on cancer” was founded upon the premise that an understanding of tumor biology would lead to effective cancer treatments. This philosophy is embodied by profiling studies that search the molecular signatures of tumors for indicators of effective treatment options. Initially, these studies were predicated on the notion that the discovery of so-called “driver mutations” would afford therapeutic opportunities. Although the strategy of targeting these alterations has produced stunning responses, these effects are invariably short-lived, as the plasticity of cancer cells allows them to evade these targeted therapies. Underlying this resistance is the ability of cancer cells to manipulate other tumor cells types into providing an environment that is protective against therapeutic onslaught. It is now argued that curative responses will only be achieved by understanding and targeting these cellular interactions.
The goal of the Knott Lab is to develop cancer treatment strategies that are focused on the interactions between malignant and non-malignant tumor cells, which drive disease progression. This work entails developing and interrogating models of resistance to established and experimental therapies. In addition, the lab applies novel profiling methods to study patient tumors so that the cellular interactions driving the diseased tissue can be ascertained. By applying the knowledge that is gained from studying clinical material to focus questions asked of the model systems, the lab hopes to identify rationally guided therapeutic strategies to halt disease progression.
OLIVER BRAUBACH, PHD
Oliver is a neurobiologist with a long standing interest in microscopy and optogenetics. He obtained his doctorate from Dalhousie University in 2011 his work on the zebrafish brain. He then completed postdoctoral appointments at Yale and the Korea Institute of Science and Technology doing in vivo calcium imaging in mice. Oliver joined to Knott lab in 2019 so that he can partake in the development of MERFISH and CODEX imaging platforms. These platforms enable highly multiplexed optical analysis of gene and protein expression in intact tissue samples. Oliver’s goal is to make these platforms widely available to researchers at Cedars Sinai.
FEB. 2018; NATURE
Asparagine availability governs metastasis in a model of breast cancer.
Knott SRV*, Wagenblast E*, Kim SY, Soto M, Khan S, Gable AL, Maceli AR, Dickopf S, Erard N, Harrell C, Perou CM, Wilkinson JE, Hannon GJ. (*first author)
Nature. 2018 Feb 7. doi: 10.1038/nature25465
JUL. 2017;MOL CELL
A CRISPR Resource for Individual, Combinatorial, or Multiplexed Gene Knockout.
Erard N, Knott SRV, Hannon GJ.
Mol Cell. 2017 Jul 20;67(2):348-354.e3. doi: 10.1016/j.molcel.2017.06.030.
A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis.
Wagenblast E, Soto M, Gutiérrez-Ángel S, Hartl CA, Gable AL, Maceli AR, Erard N, Williams AM, Kim SY, Dickopf S, Harrell JC, Smith AD, Perou CM, Wilkinson JE, Hannon GJ, Knott SR.
Nature. 2015 Apr 16;520(7547):358-62. doi: 10.1038/nature14403. Epub 2015 Apr 8.
DEC. 2014;MOL CELL
A computational algorithm to predict shRNA potency.
Knott SR, Maceli AR, Erard N, Chang K, Marran K, Zhou X, Gordon A, El Demerdash O, Wagenblast E, Kim S, Fellmann C, Hannon GJ.
Mol Cell. 2014 Dec 18;56(6):796-807. doi: 10.1016/j.molcel.2014.10.025. Epub 2014 Nov 26.
Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.
Knott SR, Peace JM, Ostrow AZ, Gan Y, Rex AE, Viggiani CJ, Tavaré S, Aparicio OM.
Cell. 2012 Jan 20;148(1-2):99-111. doi: 10.1016/j.cell.2011.12.012.