- ASSISTANT PROFESSOR Pharmacology and Systems Therapeutics
BS, Georgia Institute of Technology
PhD, University of Delaware
Postdoctoral Training, University College Dublin
- Dr. Birtwistle is an Assistant Professor in the Department of Pharmacology and Systems Therapeutics.
Dr. Birtwistle is formally trained as a chemical engineer, and thus knowledgeable in a wide array of quantitative methods for mathematical modeling of physiochemical processes. During his doctoral work, he applied such methods to understanding cancer as a disease of deregulated control systems, particularly, the ErbB signaling network, which is dysfunctional in many types of human cancer. Such a so-called integrative systems biology approach focuses not on how individual genes and proteins affect the signaling network, but rather on how the connectivity between and states of players in the network create biological function, or in the case of cancer, disease. During this doctoral and consequently postdoctoral experience, Dr. Birtwistle was also trained as an experimental cell and molecular biologist to complement the quantitative modeling background, and thus brings a truly interdisciplinary approach and thinking to cancer research.
ResearchThe overarching theme of our research can be thought of as trying to decode the language that the cells within our body use. Unlike our spoken language of words, a cell encodes information in the form of chemical reactions that tell a cell what to do. We want to understand how different environmental cues outside the cell are translated into these chemical reactions-a process called signal transduction-and also consequently how a cell understands these chemical reactions in order to enact a cellular program, such as growing, moving, or dying. When we understand these processes, we will then better understand how to manipulate them for the treatment of diseases that occur when this cellular language is either distorted or misinterpreted, such as in cancer.
We apply a combination of computational modeling approaches with experimental molecular and cell biology methods to understand, predict, and then confirm how perturbations—which can include treatment with everything from hormones to cancer drugs—influence mammalian signal transduction, cell fate decisions and phenotypes. In terms of modeling and experiments we give particular emphasis to single-cell approaches, and are particularly interested in understanding both the sources and consequences of cell-to-cell variability in signal transduction, and how such noise translates into phenotypic diversity. We view the ability to predict how populations of cancer cells respond heterogeneously to various putative treatments as essential to improving targeted treatment of cancer. While the principles we explore are arguably applicable to multiple types of cancer, as a test bed, we focus on the ErbB receptor signaling network in the context of breast cancer. Overexpression of the ErbB2/HER2 receptor occurs in ~25% of all breast cancer patients and is indicative of poor prognosis, and multiple targeted treatments, such as the monoclonal antibody trastuzumab and the small molecule inhibitor lapatinib have been clinically successful.
Please see the Birtwistle Laboratory website for additional information.
Birtwistle MR, Rauch J, Kiyatkin A, Aksamitiene E, Dobrzy 324 Ski M, Hoek JB, Kolch W, Ogunnaike BA, Kholodenko BN. Emergence of bimodal cell population responses from the interplay between analog single-cell signaling and protein expression noise. BMC Systems Biology 2012 Aug; 6(1).
von Thun A, Birtwistle M, Kalna G, Grindlay J, Strachan D, Kolch W, von Kriegsheim A, Norman JC. ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-β2. Journal of Cell Science 2012 Mar; 125(Pt 6).
Birtwistle MR, von Kriegsheim A, Kida K, Schwarz JP, Anderson KI, Kolch W. Linear approaches to intramolecular Förster resonance energy transfer probe measurements for quantitative modeling. PloS One 2011; 6(11).
Matallanas D, Birtwistle M, Romano D, Zebisch A, Rauch J, von Kriegsheim A, Kolch W. Raf family kinases: old dogs have learned new tricks. Genes & Cancer 2011 Mar; 2(3).
Birtwistle MR, Kolch W. Biology using engineering tools: the negative feedback amplifier. Cell Cycle 2011 Jul; 10(13).
Sturm OE, Orton R, Grindlay J, Birtwistle M, Vyshemirsky V, Gilbert D, Calder M, Pitt A, Kholodenko B, Kolch W. The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier. Science Signaling 2010; 3(153).
Nakakuki T, Birtwistle MR, Saeki Y, Yumoto N, Ide K, Nagashima T, Brusch L, Ogunnaike BA, Okada-Hatakeyama M, Kholodenko BN. Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics. Cell 2010 May; 141(5).
Kholodenko BN, Birtwistle MR. Four-dimensional dynamics of MAPK information processing systems. Wiley Interdisciplinary Reviews. Systems Biology and Medicine; 1(1).
von Kriegsheim A, Baiocchi D, Birtwistle M, Sumpton D, Bienvenut W, Morrice N, Yamada K, Lamond A, Kalna G, Orton R, Gilbert D, Kolch W. Cell fate decisions are specified by the dynamic ERK interactome. Nature Cell Biology 2009 Dec; 11(12).
Birtwistle MR, Kholodenko BN. Endocytosis and signalling: a meeting with mathematics. Molecular Oncology 2009 Aug; 3(4).
Birtwistle MR, Hatakeyama M, Yumoto N, Ogunnaike BA, Hoek JB, Kholodenko BN. Ligand-dependent responses of the ErbB signaling network: experimental and modeling analyses. Molecular Systems Biology 2007; 3.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr.Birtwistle is not currently required to report Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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