Research in the Birtwistle Lab is at the crossroads between engineering and mammalian biology, in an emerging area called mammalian systems biology. In general we are motivated by either biological questions that can be answered using a combination of biology and engineering methods, or medical and engineering problems that can be solved by exploiting biological and engineering knowledge. Our unifying theme is understanding how the biochemical language of mammalian cellular signaling translates into both single-cell and population level phenotypic behavior, followed by exploitation of this understanding to advance engineering and medicine. A particular focus involves cellular decisions regarding proliferation and invasion in transformed and untransformed cells, and how such decisions may be related to drug sensitivity and resistance in cancer. We are one of the few labs in the world that combines cutting edge experimental biology with deep theoretical and computational research.
This theme is the glue that holds together three main research areas: (1) developing new and improving existing methodologies for how to construct, simulate, discriminate, and validate mathematical models of mammalian signaling and cell-fate decision processes such as those involved in transformation, progression to metastasis, and development of drug resistance, (2) understanding the sources and controllability of biological noise, and the consequences of this noise for practical manipulation of signaling and phenotypes, and (3) generating predictive mathematical models of cellular signaling processes to enable rational design and control of cell-fate decisions in biological systems (natural and engineered).
Our research is applicable to many fields in medicine, where understanding how to manipulate mammalian cell fates is crucial for applications ranging from cancer to diabetes to stem cell therapy. Currently, we focus on breast cancer, and in particular understanding differential signaling and cell-fate decisions in two cell lines: the non-transformed MCF10A and highly invasive MCF10CA1 mammary epithelial cells. CA1 cells were generated from 10A cells by transforming with oncogenic Ras, and then injecting the Ras-transformed 10A cells into mice, waiting for spontaneous tumor and metastasis formation, harvesting the malignancies, and repeating the process several times (Santner et al., Breast Cancer Res Treat 65: 101-110, 2001). Thus, CA1 cells are an evolved, malignant version of 10A cells.
Marc Birtwistle PhD
1468 Madison Ave
Floor 19 Room 19-80A
One Gustave L. Levy Place
New York, NY 10029