Painting life in the lab

Featuring

• Ross Cagan (Mount Sinai Hospital Developmental & Regenerative Biology Program)
• Jennifer Toth (Paint & Collage)

Overview

The Cagan Lab uses the fruit fly (scientific name = Drosophila) to model human disease mechanisms and therapeutics, primarily for cancer and also diabetes. Research in the Cagan lab incorporates genetic and drug screening approaches in fruit flies, and uses fruit fly characteristics and/or fruit fly survival as a readout for potential drug targets. By combining Drosophila genetics and medicinal chemistry to develop a new generation of lead compounds that emphasize “balanced polypharmacology” (drug compounds active against multiple disease targets), the Cagan lab has identified novel mechanisms that direct transformed cells into the first steps towards metastasis. Work from the Cagan lab has also helped validate the drug vandetanib as a therapeutic for Medullary Thyroid Carcinoma. Combining these basic research approaches, Dr. Cagan has established the Center for Personalized Cancer Therapeutics, in which new tools including ‘personalized Drosophila avatars’ are developed and used to screen for personalized human drug cocktails.

The Cagan lab uses the fruitfly as an animal in which to replicate DNA sequences of particular cancerous tumors from patients and find drug cocktails that will best target those tumors.  I was fascinated by the idea of eyes as a theme connecting the scientists, their flies, and ultimately my artwork.  The scientists are looking for new solutions, the eyes of the fruit flies are being morphed and distorted by tumors and reversed by drugs, and my vision is yet another layer of looking.  Time in the Cagan lab was spent drawing directly from the artist’s observations of the equipment and people at work. Toth's artwork includes drawings, a small felt tapestry, collages, & a final painting.

The final pieces include images of eyes, of microscopes, of scientists working, and of distortions as if these various forms of seeing are being affected by changing visions.  The final result, incorporates different painting techniques and different materials than the artist would normally use, as an effort to stretch the artistic vision and try new solutions in the spirit of the kind of imaginative investigating happening in the Cagan lab. “I learned so much from my time in the Cagan lab, and saw scientists discovering new solutions with such passion, intelligence, & innovation.”

Bios

Jennifer Toth

Paint & Collage

Jenny Toth is a painter and collage artist living and working in New York City. She received her B.A. from Smith College in Studio Art in 1994, and her M.F.A. from Yale School of Art in 1998. She also spent two years studying at The New York Studio School. She is currently an Associate Professor of Art at Wagner College on Staten Island. Jenny is represented by The George Gallery, Laguna Beach, CA, and Tabla Rasa Gallery in Brooklyn. She was recently a member of SOHO20 Gallery and is currently a member of Blue Mountain Gallery in NYC. In recent years she has spent much of her time living and working in San Miguel de Allende, Mexico where she finds inspiration. Jenny’s work is based in direct observation from life. She explores ways of isolating fragments, dismantling them, and recombining them in disjointed ways.

Ross Cagan

Mount Sinai Hospital
Developmental & Regenerative Biology Program

Cancer has proven a difficult disease to achieve significant long-term advances in patient survival; improvements in survival are often measured in months. Diabetes has not fare much better. Dr. Cagan’s laboratory uses Drosophila (fruit fly) as an experimental model to address disease mechanisms and therapeutics, primarily for cancer and diabetes. Taking advantage of the fly, the Cagan lab uses a whole animal and integrated approach in studying disease: genes and drugs identified in flies are then brought to rodent (such as mouse models) and ultimately to clinical trials in humans; sequencing and histological data from humans are then brought back to our fly models to allow us to develop increasingly sophisticated dipteran (insect) tools.

More specifically, in cancer, their work helped validate the drug, vandetanib, as a therapeutic for Medullary Thyroid Carcinoma; combined Drosophila genetics and medicinal chemistry to develop a new generation of lead compounds that emphasize “balanced polypharmacology”; and identified novel mechanisms that direct transformed (cancerous) cells into the first steps towards metastasis. Regarding diabetes, his laboratory has identified mechanisms that direct diabetic cardiomyopathy and nephropathy as well as a new network through which diabetic patients are at heightened risk for aggressive tumors.

Dr. Cagan along with colleagues at Mt. Sinai has established the Center for Personalized Cancer Therapeutics, which by combining the basic research approaches discussed above aims to create new tools including ‘personalized Drosophila avatars’ that are being developed and used to screen for personalized drug cocktails.

Another fundamental interest of the Cagan laboratory is the basic understanding of epithelial patterning and how does an initially random collection of undifferentiated (naïve, undeveloped) cells mature into a precise and functional organized epithelium? The developing Drosophila eye is an elegant model for studying epithelial patterning and, incidentally, is one of nature’s most beautiful structures. Once the early pattern of photoreceptors are laid down, a progressive stepwise program of recruitment gathers the other 13 cells required to create the core of each unit eye or ‘ommatidium’. Remaining is a ‘sea’ of undifferentiated (naïve, undeveloped) interommatidial precursor cells (IPCs). These IPCs will differentiate (develop) as 2 cells that form an interweaving hexagonal lattice around the ommatidia, and the rest are killed off to tighten the pattern. In order to more clearly understand how such eye patterning is controlled, we have closely examined the role of transmembrane adhesion molecules expressed in IPCs. Adhesion molecules are proteins located on the cell surface involved in binding with other cells or with the extracellular matrix (ECM) between cells. We find that, one adhesion molecule in particular, called Rst, it directs hexagonal pattern in the eye by binding to the transmembrane protein, Hibris (Hbs), on the surface of cells within the neighboring ommatidial cores. These results suggest a model in which the drive to maximize Rst/Hbs binding drives cells into their proper niche and/or pattern. The Cagan lab is currently testing whether simple adhesion is sufficient to direct cells into a hexagonal, honeycomb pattern through experiments and through computer modeling. Implicit in this model is the idea that adhesion, not signal transduction, is paramount.